Papers

Razavi H, Robbins S, Zeuzem S, Negro F, Buti M, Duberg A-S, et al. Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study. The Lancet Gastroenterology & Hepatology.2(5):325-36.

Background: Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods: We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings: We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000–3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0·64% (95% UI 0·41–0·74). We estimated that 1 180 000 (95% UI 1 003 000–1 357 000) people were diagnosed with viraemia (36·4%), 150 000 (12 000–180 000) were treated (4·6% of the total infected population or 12·7% of the diagnosed population), 133 000 (106 000–160 000) were cured (4·1%), and 57 900 (43 900–67 300) were newly infected (1·8%) in 2015. Additionally, 30 400 (26 600–42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025. Interpretation: Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary. Funding: Gilead Sciences.

Gunter J, Callens S, De Wit S, Goffard J-C, Moutschen M, Darcis G, et al. Prevalence of non-infectious comorbidities in the HIV-positive population in Belgium: a multicenter, retrospective study. Acta Clinica Belgica. 2017:1-4.

Abstract: Objectives: In Belgium, eleven AIDS Reference Centers (ARCs) and seven AIDS Reference Laboratories diagnose and treat HIV-positive individuals and track patients under care. As AIDS-related deaths are avoided and the HIV-positive population ages, non-infectious comorbidities (NICMs), such as cardiovascular disease, renal disease and certain cancers, play a larger role in the quality and length of patients’ lives. This study aims to characterize the HIV-positive population in Belgium in terms of the prevalence of key NICMs. Methods: We performed a retrospective study of 5787 HIV-positive patients under follow-up at four ARCs across Belgium between 1st of June 2014 and 1st of July 2016. Results: The mean age of patients under follow-up was 46.7 (SD = 11.6) years, and the mean nadir CD4 count was 268.8 cells/mm3 (SD = 189.5). The prevalence of diabetes mellitus, arterial hypertension and chronic kidney disease (CKD) were 5.9, 31 and 7.8%, respectively. Cardiovascular events, defined as the occurrence of myocardial infarction, stroke or an invasive coronary procedure, occurred in 2.9% of patients. The highest age-adjusted mortality rates were observed among patients 51–55 years of age. Mortality rates were also higher among patients with CKD and patients with viremic hepatitis C virus (p < 0.05). Conclusions: Helping the aging HIV-positive population avoids premature morbidity and mortality from NICMs represents a key challenge to further improve patient outcomes. Belgium has an advanced system of HIV care and patient management; however, standardized data collection across ARCs is needed to improve knowledge sharing and to support future countrywide analyses.

Manns MP, Buti M, Gane E, Pawlotsky JM, Razavi H, Terrault N, et al. Hepatitis C virus infection. Nature reviews Disease primers. 2017;3:17006.

Abstract: Hepatitis C virus (HCV) is a hepatotropic RNA virus that causes progressive liver damage, which might result in liver cirrhosis and hepatocellular carcinoma. Globally, between 64 and 103 million people are chronically infected. Major risk factors for this blood-borne virus infection are unsafe injection drug use and unsterile medical procedures (iatrogenic infections) in countries with high HCV prevalence. Diagnostic procedures include serum HCV antibody testing, HCV RNA measurement, viral genotype and subtype determination and, lately, assessment of resistance-associated substitutions. Various direct-acting antiviral agents (DAAs) have become available, which target three proteins involved in crucial steps of the HCV life cycle: the NS3/4A protease, the NS5A protein and the RNA-dependent RNA polymerase NS5B protein. Combination of two or three of these DAAs can cure (defined as a sustained virological response 12 weeks after treatment) HCV infection in >90% of patients, including populations that have been difficult to treat in the past. As long as a prophylactic vaccine is not available, the HCV pandemic has to be controlled by treatment-as-prevention strategies, effective screening programmes and global access to treatment.

Hajarizadeh B, Grebely J, McManus H, Estes C, Razavi H, Gray RT, et al. Chronic hepatitis C burden and care cascade in Australia in the era of interferon-based treatment. J Gastroenterol Hepatol. 2017;32(1):229-36.

Abstract: Background and Aim - Interferon-free direct-acting antiviral regimens for hepatitis C virus (HCV) infection have been recently available in Australia, beginning a new era in clinical and public health management of HCV infection. This study provided updated estimates of the HCV infection care cascade and burden in Australia as a reliable platform for assessing the future impact of interferon-free therapies. Methods: A modeling approach was applied to estimate the number of individuals living with chronic HCV infection and with various liver disease stages. Data from national registries of HCV notification and liver transplantation, literature review, and expert consensus informed the model parameters. HCV notification and Pharmaceutical Benefits Scheme data were used to estimate the number of HCV diagnosed individuals and treatment uptake. Results: In 2014, an estimated 230 470 individuals (range: 180 490–243 990) were living with HCV, among whom 75% were diagnosed (n = 172 720; range: 156 720–188 770), 20% had ever received treatment (n = 45 000; range: 39 280–50 720), and 11% had been cured (n = 24 750; range: 21 520–27 990). Among individuals with HCV infection, the proportion with hepatic fibrosis stage ≥F3 doubled during the last decade, increasing from 9% (n = 18 580) in 2004 to 19% (n = 44,730) in 2014. Individuals initiating HCV treatment increased from 1100 in 1997 to 3840 in 2007, plateaued until 2010 and decreased to 2790 in 2014. Conclusions: The burden of HCV-related liver disease has increased markedly. Although the proportion diagnosed was high, treatment uptake remained low, with no increase over the last 7 years. Reducing the HCV burden in Australia requires scale-up of interferon-free HCV therapies.

Robaeys G, Bielen R, Azar DG, Razavi H, Nevens F. Global genotype distribution of hepatitis C viral infection among people who inject drugs. J Hepatol. 2016;65(6):1094-103.

Abstract: Hepatitis C viral infection after injection drug use is very prevalent. The most important genotype causing HCV infection in PWID globally is genotype 1, as is the case in the general population, but also genotype 3 is highly prevalent in PWID. Genotype 4 is most prevalent in Africa, spreading into Europe, whereas genotype 2 and 6 are more located in Asia. The most important difference comparing to the general population are generally lower prevalence of genotype 1b, and higher prevalence of genotype 1a and 3 in PWID. As the genotype nowadays still determines the treatment, and as there is a different genotype distribution than in the general population, it is important to identify the genotype also in PWID.

Rodrigo C, Eltahla AA, Bull RA, Grebely J, Dore GJ, Applegate T, et al. Historical Trends in the Hepatitis C Virus Epidemics in North America and Australia. J Infect Dis. 2016;214(9):1383-9.

Abstract: BACKGROUND:  Bayesian evolutionary analysis (coalescent analysis) based on genetic sequences has been used to describe the origins and spread of rapidly mutating RNA viruses, such as influenza, Ebola, human immunodeficiency virus (HIV), and hepatitis C virus(HCV). METHODS:  Full-length subtype 1a and 3a sequences from early HCV infections from the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC3), as well as from public databases from a time window of 1977-2012, were used in a coalescent analysis with BEAST software to estimate the origin and progression of the HCV epidemics in Australia and North America. Convergent temporal trends were sought via independent epidemiological modeling. RESULTS:  The epidemic of subtype 3a had more recent origins (around 1950) than subtype 1a (around 1920) in both continents. In both modeling approaches and in both continents, the epidemics underwent exponential growth between 1955 and 1975, which then stabilized in the late 20th century. CONCLUSIONS:  Historical events that fuelled the emergence and spread of injecting drug use, such as the advent of intravenous medical therapies and devices, and growth in the heroin trade, as well as population mixing during armed conflicts, were likely drivers for the cross-continental spread of the HCV epidemics.

Aljumah AA, Abaalkhail F, Al-Ashgar H, Assiri A, Babatin M, Al Faleh F, et al. Epidemiology, disease burden, and treatment strategies of chronic hepatitis C virus infections in Saudi Arabia in the new treatment paradigm shift. Saudi J Gastroenterol. 2016;22(4):269-81.CITE

Abstract: Background/Aims: Around 101,000 individuals are estimated to be viremic for chronic hepatitis C virus (HCV) in the Kingdom of Saudi Arabia (KSA) in 2014; however, only about 20% have been diagnosed. We aim to assess baseline epidemiology, disease burden, and evaluate strategies to eliminate HCV in KSA. Materials and Methods: The infected population and disease progression were modeled using age- and gender-defined cohorts to track HCV incidence, prevalence, hepatic complications, and mortality. Baseline assumptions and transition probabilities were extracted from the literature. The impacts of two scenarios on HCV-related disease burden were considered through increases in treatment efficacy alone or treatment and diagnosis. Results: In 2030, it is estimated by the base scenario that viremic prevalence will increase to 103,000 cases, hepatocellular carcinoma (HCC) to 470, decompensated and compensated cirrhosis cases to 1,300 and 15,400, respectively, and liver-related mortality to 670 deaths. Using high efficacy treatment alone resulted in 2030 projection of 80,700 viremic cases, 350 HCC cases, 480 liver-related deaths, and 850 and 11,500 decompensated and compensated cirrhosis cases, respectively. With an aggressive treatment strategy, in 2030 there will be about 1,700 viremic cases, 1 HCC case, about 20 liver-related deaths, and 5 and 130 cases of decompensated and compensated cirrhosis, respectively. Delaying this strategy by one year would result in 360 additional deaths by 2030. Conclusions: HCV in KSA remains constant, and cases of advanced liver disease and mortality continue to rise. Considered increases in treatment efficacy and number treated would have a significantly greater impact than increased treatment efficacy alone. The projected impact will facilitate disease forecasting, resource planning, and strategies for HCV management. Increased screening and diagnosis would likely be required as part of a national strategy.

Blach S, Zeuzem S, Manns M, Altraif I, Duberg A-S, Muljono DH, et al. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. The Lancet Gastroenterology & Hepatology.

Background: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods: We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings: Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1•0% (95% uncertainty interval 0•8–1•1) in 2015, corresponding to 71•1 million (62•5–79•4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation: The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding: John C Martin Foundation.

Bourgeois S, Blach S, Brixko C, Laleman W, Mathei C, Mulkay JP, et al. Achieving WHO recommendations for Hepatitis C Virus Elimination in Belgium. Acta Gastroenterol Belg. 2016;79(2):222-6.

BACKGROUD: The World Health Organization (WHO) released updated guidelines for the screening, care and treatment of patients with chronic hepatitis C virus (HCV) infection. METHODS: A previously described HCV disease burden model was used to develop a "WHO scenario" to achieve the WHO recommendations of a 90% reduction in incidence and 65% reduction in liver-related deaths. After determining the steps necessary to achieve this goal, the impact of realistic constraints was modeled. RESULTS: In 2015, there were 66.200 viremic infections, with 43% diagnosed and 1.350 treated. In order to reduce new infections, treatment must be extended to ≥ F0 patients, including people who inject drugs and other individuals at risk of transmitting HCV. -Additionally, diagnosis and treatment of 3.030 and 4.060 patients, respectively, would be required. The largest attenuation of the WHO scenario would occur if no new cases were diagnosed after 2018 (300% more viremic infections by 2030). Limiting treatment to ≥ F2 patients or treating fewer patients (3.000) would result in 220% or 140% more viremic cases, respectively, compared with the WHO scenario. CONCLUSION: Achieving the WHO guidelines in Belgium requires a coordinated effort to scale up treatment and prevention efforts and to allow treatment access to patients of all fibrosis stages. A scale-up of treatment, however, requires patients to be both diagnosed and linked to care, suggesting a need for increased awareness and expanded screening efforts. Finally, prevention of new HCV infections requires a comprehensive understanding of the population at risk of transmitting HCV.

Mathei C, Bourgeois S, Blach S, Brixko C, Mulkay JP, Razavi H, et al. Mitigating the burden of hepatitis C virus among people who inject drugs in Belgium. Acta Gastroenterol Belg. 2016;79(2):227-32.

BACKGROUD AND AIMS: In 2010, there were an estimated 10 100 PWID in Belgium and 43% (34%-57%) were HCV infected. Understanding HCV transmission dynamics in high-risk populations and assessing the potential impact of improved HCV treatment strategies requires robust epidemiological data and mathematical modeling. METHODS: HCV transmission was modeled using cohorts to track HCV incidence and prevalence among active PWID in the general PWID population, OST and NSP. Model assumptions were derived from published literature and expert consensus. The relative impact of increasing the number of PWID treated with new oral DAAs was considered. RESULTS: If the current transmission paradigm continues, there will be 2645 HCV-infected PWID in 2030. Annually treating 30 (1% of 2015 population) or 120 (4% of 2015 population) HCV-infected PWID with oral DAAs will result in 5% and 25% reductions, respectively, in HCV-infected PWID by 2030. Treating 370 PWID annually (12.5% of 2015 population) will result in a > 90% reduction by 2030. CONCLUSION: Treating a small number of PWID can result in substantial reduction in HCV prevalence in this population ; however, high levels of treatment are necessary to reduce the viral pool and thus the risk of secondary infections. This analysis supports implementation of a screening and treatment strategy among PWID when combined with an expansion of harm reduction programs.

Elimination of hepatitis C in Spain: Adaptation of a mathematical model based on the public health strategic plan for addressing hepatitis C in the National Health System. Maria Buti, Jose Luis Calleja, Javier Garcia-Samaniego, Miguel Angel Serra, Javier Crespo, Manuel Romero, Miguel Angel Simon, Juan Turnes, Antonio Javier Blasco, Pablo Lazaro, Sarah Robbins and Homie Razavi. Medicine Clinica 2017 (in press).

This article is in press.

Hepatitis B and C in the Spotlight. A public health response in the Americas, 2016. Washington, D.C. : PAHO; 2016.

Gountas I, Sypsa V, Papatheodoridis G, et al. Is elimination of HCV possible in a country with low diagnostic rate and moderate HCV prevalence? The case of Greece. Journal of Gastroenterology and Hepatology July 2016.

Background & Aim: The treatment of hepatitis C (HCV) with interferon (IFN)-free Direct-Acting Antivirals (DAAs) is anticipated to change the future burden of disease. Aim of this study is to quantify the impact of IFN-free DAAs on HCV-related morbidity and mortality in Greece under different scenarios concerning treatment coverage and primary prevention, including the proposed by World Health Organization Global Hepatitis Strategy. Methods: A previously described model was used to project the future disease burden up to 2030 under scenarios which includes treatment based on the combination of pegylated-IFN with ribavirin (base case) and scenarios using DAAs therapies. Results: Under the base case scenario, an increase in HCV-related morbidity and mortality is predicted in Greece (mortality in 2030: +23.6% compared to 2015). If DAAs are used with the same treatment coverage, the number of hepatocellular carcinoma cases and of liver related deaths are predicted to be lower by 4%-7% compared to 2015. Under increased treatment coverage (from 2,000 treated/year to approximately 5,000/year in 2015-2020 and 2,500/year subsequently), morbidity and mortality will decrease by 43%-53% in 2030 compared to 2015. To achieve the WHO Global Hepatitis Strategy goals, a total number of 86,500 chronic hepatitis C patients will have to be treated during 2016-2030. Conclusions: Elimination of HCV in Greece by 2030 necessitates great improvements in primary prevention, implementation of large screening programs and high treatment coverage.

Soipe A, Razavi H, Razavi-Shearer D, et al. Chronic hepatitis C virus (HCV) burden in Rhode Island:
modelling treatment scale-up and elimination. Epidemiology & Infection August 2016.

We utilized a disease progression model to predict the number of viraemic infections, cirrhotic cases, and liver-related deaths in the state of Rhode Island (RI) under four treatment scenarios: (1) current HCV treatment paradigm (about 215 patients treated annually, Medicaid reimbursement criteria fibrosis stage 5F3); (2) immediate scale-up of treatment (to 430 annually) and less restrictive Medicaid reimbursement criteria (fibrosis stage 5F2); (3) immediate treatment scale-up and no fibrosis stage-specific Medicaid reimbursement criteria (5F0); (4) an ‘elimination’ scenario (i.e. a continued treatment scale-up needed to achieve >90% reduction in viraemic cases by 2030). Under current treatment models, the number of cirrhotic cases and liver-related deaths will plateau and peak by 2030, respectively. Treatment scale-up with 5F2 and 5F0 fibrosis stage treatment criteria could reduce the number of cirrhotic cases by 21·7% and 10·0%, and the number of liver-related deaths by 19·3% and 7·4%, respectively by 2030. To achieve a >90% reduction in viraemic cases by 2030, over 2000 persons will need to be treated annually by 2020. This strategy could reduce cirrhosis cases and liver-related deaths by 78·9% and 72·4%, respectively by 2030. Increased HCV treatment uptake is needed to substantially reduce the burden of HCV by 2030 in Rhode Island.

Hajarizadeh B, Razavi-Shearer D, Merat S, et al. Liver Disease Burden of Hepatitis C Virus Infection in Iran and the Potential Impact of Various Treatment Strategies on the Disease Burden. Hepatitis Monthly July 2016.

Background: Chronic hepatitis C virus (HCV) infection is emerging as the leading cause of viral hepatitis-related liver disease in Iran. Objectives: This study estimated the current and future disease burden of HCV infection in Iran and assessed the impact of various strategies in access to HCV treatment on reducing the disease burden. Materials and Methods: A modelling approach was used to estimate the size of HCV infected population, and disease progression from 2014 to 2030. Literature review and expert consensus informed the model parameters. Base case scenario assumed the currently utilized Interferon (IFN)-based treatment. Five other scenarios assumed utilizing IFN-free direct acting anti-viral regimens with 1, the base case diagnosis and treatment uptake; 2, restricting treatment to severe liver fibrosis; 3, treatment uptake being doubled; 4, stepwise increase in treatment uptake (doubled by 2017, quadrupled thereafter); 5, targeting at least 90% reduction in HCV infections by 2030. Results: In 2014, an estimated 186,500 individuals are living with HCV infection in Iran (median age: 30 years). By 2030, this number will increase to 213,700, while three to four fold increase is expected in the case numbers of decompensated cirrhosis (DC, n = 620), hepatocellular carcinoma (HCC, n = 510), and liver disease death (n = 400), assuming the current diagnosis/treatment settings. As compared with the base case scenario, scenarios 1 and 2 will have a limited impact on HCV disease burden, while scenarios 3 and 4 will result in 45% - 49% decrease in the number of individuals living with HCV infection and 60% - 69% decrease in DC, HCC and liver disease deaths by 2030. For at least 90% reduction in HCV infections by 2030 (scenario 5), diagnosis and treatment rates should be increased to 12,000 and 9,000 individuals per year in 2016, respectively and to 24,000 and 18,000 individuals per year, respectively in 2018 onward. Conclusions: An increasing burden of HCV-related liver disease is expected in Iran under the current diagnosis and treatment levels. Increased diagnosis and treatment uptake is required in combination with enhanced treatment efficacy to reduce the HCV burden. The relatively young age of the HCV infected population, provides an opportunity for timely interventions to avert the projected rising HCV disease burden in Iran..

Platt L, Easterbrook, Gower E, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis 2016.

Background At global level, there are 37 million people infected with HIV and 115 million people with antibodies to hepatitis C virus (HCV). Little is known about the extent of HIV–HCV co-infection. We sought to characterise the epidemiology and burden of HCV co-infection in people living with HIV. Methods In this systematic review and meta-analysis we searched MEDLINE, Embase, CINAHL+, POPLINE, Africa wide Information, Global Health, Web of Science, and the Cochrane Library and WHO databases for studies measuring prevalence of HCV and HIV, published between Jan 1, 2002, and Jan 28, 2015. We included studies in HIV population samples of more than 50 individuals and recruited patients based on HIV infection status or other behavioural characteristics. We excluded editorials or reviews containing no primary data, samples of HCV or HIV–HCV co-infected individuals, or samples relying on self-reported infection status. We also excluded samples drawn from populations with other comorbidities or undergoing interventions that put them at increased risk of coinfection. Populations were categorised according to HIV exposure, with the regional burden of co-infection being derived by applying co-infection prevalence estimates to published numbers of HIV-infected individuals. We did a meta-analysis to estimate the odds of HCV in HIV-infected individuals compared with their HIV-negative counterparts. Findings From 31 767 citations identified, 783 studies met the inclusion criteria, resulting in 902 estimates of the prevalence of HIV–HCV co-infection. In HIV-infected individuals, HIV–HCV co-infection was 2•4% (IQR 0•8–5•8) within general population samples, 4•0% (1•2–8•4) within pregnant or heterosexually exposed samples, 6•4% (3•2–10•0) in men who have sex with men (MSM), and 82•4% (55•2–88•5) in people who inject drugs (PWID). Odds of HCV infection were six times higher in people living with HIV (5•8, 95% CI 4•5–7•4) than their HIV-negative counterparts. Worldwide, there are approximately 2 278 400 HIV–HCV co-infections (IQR 1 271 300—4 417 000) of which 1 362 700 (847 700–1 381 800) are in PWID, equalling an overall co-infection prevalence in HIV-infected individuals of 6•2% (3•4–11•9). Interpretation We noted a consistently higher HCV prevalence in HIV-infected individuals than HIV-negative individuals across all risk groups and regions, but especially in PWID. This study highlights the importance of routine HCV testing in all HIV-infected individuals, but especially in PWID. There is also a need to improve country level surveillance of HCV prevalence across different population groups in all regions

Bruggmann P, Negro F, Bihl F, et al. Birth cohort distribution and screening for viraemic hepatitis C virus infections in Switzerland. Swiss Med Wkly. 2015.

OBJECTIVE: In Switzerland, fewer than 40% of hepatitis C virus (HCV) infected individuals have been diagnosed. The aim of this project was to analyse the distribution of HCV cases in order to develop better detection strategies. STUDY DESIGN: Historical data on the HCV-infected population in Switzerland were obtained from published literature, unpublished data and government reports. A disease progression model was used to age the infected population to 2015. The HCV distribution was then used to identify 5-year age cohorts with the highest HCV prevalence. The estimated number of cases needed to screen within an age cohort was calculated using the estimated viraemic prevalence, removing the percent previously diagnosed. RESULTS: In 2015, the median age of the viraemic HCV infected population was 49 years, with 75% of the population born between 1951 and 1985. Random screening of the general population could identify one new viraemic HCV case per 159 persons screened, compared with targeted birth cohort screening, which could identify one new viraemic HCV case per 90–99 persons screened. CONCLUSION: Considering only the direct cost of screening and treatment informing tests, targeted screening by birth cohort is more effective and cost effective than random screening in the general population.

Ferreira PRA, Brandão-Mello CE, Estes C, et al. Disease burden of chronic hepatitis C in Brazil. Braz J Infect Dis. 2015;19(4):363-368.

Background: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective.Methods: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2).Results: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n = 325,900) and decompensated (n = 45,000) cirrhosis; hepatocellular carcinoma (n = 19,100); and liver-related deaths (n = 16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively

Forouzanfar MH, Alexander L, Ross Anderson H, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Dec 5;386(10010):2287-323.

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handvwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57•2% (95% uncertainty interval [UI] 55•8–58•5) of deaths and 41•6% (40•1–43•0) of DALYs. Risks quantified account for 87•9% (86•5−89•3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11•3 million deaths and 241•4 million DALYs, high systolic blood pressure for 10•4 million deaths and 208•1 million DALYs, child and maternal malnutrition for 1•7 million deaths and 176•9 million DALYs, tobacco smoke for 6•1 million deaths and 143•5 million DALYs, air pollution for 5•5 million deaths and 141•5 million DALYs, and high BMI for 4•4 million deaths and 134•0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and hand washing. In women, in nearly all countries in the Americas, North Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Kelly E, Blach S, Razavi H, Cooper C. Interferon-based hepatitis C antiviral treatment outcomes may be predicted by alanine aminotransferase levels. Can J Gastroenterol Hepatol. 2015 Nov-Dec;29(8):407-8.

Murray CJ, Barber RM, Foreman KJ, et al. Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: quantifying the epidemiological transition. Lancet. 2015 Nov 28;386(10009):2145-91.

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6•2 years (95% UI 5•6–6•6), from 65•3 years (65•0–65•6) in 1990 to 71•5 years (71•0–71•9) in 2013, HALE at birth rose by 5•4 years (4•9–5•8), from 56•9 years (54•5–59•1) to 62•3 years (59•7–64•8), total DALYs fell by 3•6% (0•3–7•4), and age standardised DALY rates per 100 000 people fell by 26•7% (24•6–29•1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non– communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Willemse SB, Razavi-Shearer D, Zuure FR, et al. The estimated future disease burden of hepatitis C virus in the Netherlands with different treatment paradigms.Neth J Med. 2015 Nov;73(9):417-31.

Background & Aims: Prevalence of hepatitis C virus (HCV) infection in the Netherlands is low (anti-HCV prevalence 0.22%). All-oral treatment with direct-acting antivirals (DAAs) is tolerable and effective but expensive. Our analysis projected the future HCV-related disease burden in the Netherlands by applying different treatment scenarios. Methods: Using a modelling approach, the size of the HCV-viraemic population in the Netherlands in 2014 was estimated using available data and expert consensus. The base scenario (based on the current Dutch situation) and different treatment scenarios (with increased efficacy, treatment uptake, and diagnoses) were modelled and the future HCV disease burden was predicted for each scenario. Results: The estimated number of individuals with viraemic HCV infection in the Netherlands in 2014 was 19,200 (prevalence 0.12%). By 2030, this number is projected to decrease by 45% in the base scenario and by 85% if the number of treated patients increases. Furthermore, the number of individuals with hepatocellular carcinoma and liver-related deaths is estimated to decrease by 19% and 27%, respectively, in the base scenario, but may both be further decreased by 68% when focusing on treatment of HCV patients with a fibrosis stage of ≥ F2.

Aghemo A, Dore GJ, Hatzakis A, et al. Estimating HCV disease burden – volume 3 (editorial). Journal of Viral Hepatitis, 2015, 22 (Suppl. 4), 1–3.

Liakina V, Hamid S, Tanaka J, et al. Historical epidemiology of hepatitis C virus (HCV) in select countries – volume 3. Journal of Viral Hepatitis, 2015, 22 (Suppl. 3), 4–20.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden

Sibley A, Han KH, Abourached A, et al. The present and future disease burden of hepatitis C virus infections with today’s treatment paradigm – volume 3. Journal of Viral Hepatitis, 2015, 22 (Suppl. 4), 21–41.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Alfaleh FZ, Nugrahini N, Maticic M, et al. Strategies to manage hepatitis C virus infection disease burden – volume 3. Journal of Viral Hepatitis, 2015, 22 (Suppl. 4), 42–65.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: [1] increased treatment efficacy while holding the annual number of treated patients constant and [2] increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Estes C, Abdel-Kareem M, Abdel-Razek W, et al. Economic burden of hepatitis C in Egypt: the future impact of highly effective therapies. Aliment Pharmacol Ther. 2015.

Background The prevalence of hepatitis C virus (HCV) infection in Egypt is the highest in the world, yet the total economic burden has not been quantified. Improved understanding of costs and the impact of treatment strategies will provide for better allocation of resources to reduce HCV disease and economic burden. Aim A modelling approach was used to quantify the current HCV-infected population, future disease progression and associated costs in Egypt. Methods Direct healthcare costs were calculated from a nationally representative hospital and a disability adjusted life year (DALY) template was used with monetary value assigned to lost life years. Three scenarios were considered: (i) Historical treatment scenario: 50% SVR; 65 000 treated annually, (ii) Current treatment scenario: 90% sustained virologic response (SVR); 65 000 treated annually, (iii) Increased treatment scenario: 90% SVR; 325 000 treated annually by 2018. Results Cumulative DALYs (2015–2030) under Scenario 1 were estimated at 7.88 million and cumulative costs estimated at $89.07 billion. Annual DALYs increased 16% during 2015–2030 while annual costs more than doubled. Scenario 2 reduced cumulative DALYs and costs by 7% and 4%, respectively. Under Scenario 3, total costs declined 73% to $1047 million during 2015–2030. As compared to Scenario 1, cumulative DALYs and costs decreased 37% and 35%, respectively. Conclusions This is the first estimate of the total economic burden of HCV in Egypt. Extraordinary measures are necessary to substantially reduce HCV disease and cost burden. With newer therapies, strategies to reduce disease burden are feasible and cost-effective.

Stärkel P, Vandijck D, Laleman W, et al. The disease burden of hepatitis C in Belgium : an update of a realistic disease control strategy. Acta Gastroenterol Belg. 2015; 78(2): 228-32.

Background: This manuscript serves as an update to position papers published in 2014 based on the available Belgian hepatitis C virus (HCV) epidemiological data. Methods: Building on the current standard of care (2015: 900 ≥ F3 patients treated with 70-85% SVR), four new scenarios were developed to achieve the goals of near viral elimination and prevention of HCV associated morbidity and mortality by 2026 and 2031. Increases in treatment efficacy were assumed in 2016 (90% SVR) and 2017 (95% SVR). Results: Scenario 1: Treating 6,670 patients annually by 2018 (≥ F0 beginning in 2017) and diagnosing 3,790 patients annually by 2020, a 90% reduction in viremic cases and advanced outcomes was observed by 2026. Scenario 2: Treating 4,300 patients annually by 2018 (≥ F0 beginning in 2020) without increasing the number diagnosed, a 90% reduction in viremic cases and 85%-95% reduction in advanced outcomes was observed by 2031. Scenario 3: Treating 5,000 ≥ F2 patients annually by 2018, and diagnosing 3,620 patients annually by 2020, a 90% reduction in advanced outcomes and 50% reduction in viremic cases was observed by 2026. Scenario 4: Treating 3,100 ≥ F2 patients annually by 2018 without increasing the number diagnosed, a 90%-95% reduction in advanced outcomes and 55% reduction in viremic cases was observed by 2031. Conclusions: Scenario 2 would provide the most favorable balance of outcomes (90% reduction in viremic prevalence and advanced outcomes) and realistic requirements for implementation (gradual increase in treatment, delayed incorporation of patients with no/mild fibrosis).

Müllhaupt B, Bruggmann P, Bihl F, et al. Modeling the health and economic burden of hepatitis C virus in Switzerland. PLoS ONE 2015; 10.

Background Chronic hepatitis C virus infection is a major cause of liver disease in Switzerland and carries a significant cost burden. Currently, only conservative strategies are in place to mitigate the burden of hepatitis C in Switzerland. This study expands on previously described modeling efforts to explore the impact of: no treatment, and treatment to reduce HCC and mortality. Furthermore, the costs associated with untreated HCV were modeled. Methods Hepatitis C disease progression and mortality were modeled. Baseline historical assumptions were collected from the literature and expert interviews and strategies were developed to show the impact of different levels of intervention (improved drug cure rates, treatment and diagnosis) until 2030. Results Under the historical standard of care, the number of advanced stage cases was projected to increase until 2030, at which point the annual economic burden of untreated viremic infections was projected to reach €96.8 (95% Uncertainty Interval: €36 – €232) million. Scenarios to reduce HCV liver-related mortality by 90% by 2030 required treatment of 4,190 F2 or 3,200 F3 patients annually by 2018 using antivirals with a 95% efficacy rate. Delaying the implementation of these scenarios by 2 or 5 years reduced the impact on mortality to 75% and 57%, respectively. Conclusions With today’s treatment efficacy and uptake rates, hepatitis C disease burden is expected to increase through 2030. A substantial reduction in disease burden can be achieved by means of both higher efficacy drugs and increased treatment uptake. However, these efforts cannot be undertaken without a simultaneous effort to diagnose more infections.

Sievert W. HCV-infected patients need access now to new direct-acting antiviral agents to avert liver-related deaths. MJA 2015; 202: vi.

Wedemeyer H, Dore GJ, and Ward JW. Estimates on HCV disease burden worldwide - filling the gaps. J Viral Hepat 2015; 22: (Suppl. S1), 1-5.

Hepatitis C is caused by infection with the hepatitis C virus (HCV) and represents a major global health burden. Persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma, possibly accounting for up to 0.5 million deaths every year. Treatment of HCV infection is undergoing a profound and radical change. As new treatments are extremely safe and effective, there are virtually no medical reasons to withhold therapy. Yet, the new therapies are expensive. As resources are limited, solid data to estimate the disease burden caused by HCV are urgently needed. Epidemiology data and disease burden analyses for 16 countries are presented. For almost all countries, the peak of HCV-related cirrhosis, hepatocellular carcinoma and liver-related death is a decade or more away. However, a surprising heterogeneity in country-specific HCV-associated disease burden exists. Also HCV diagnosis and treatment uptake varied markedly between countries. A consistent finding was that a reduction of HCV liver-related mortality is dependent on access to therapy. Increasing efficacy of therapy alone with a constant numbers of treatments will not have a major impact on the HCV-related disease burden. The data presented here should inform public health policy and help drive advocacy for enhanced strategic investment and action. HCV kills patients, and the disease burden will continue to rise in most countries unless action is taken soon. Chronic HCV is a curable infection and a reversible liver disease. Fortunately, the tools to eliminate HCV are now available

Saraswat V, Norris S, de Knegt RJ, et al. Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2. J Viral Hepat 2015; 22: (Suppl. S1), 6-25.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available

Hatzakis A, Chulanov V, Gadano AC, et al. The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2. J Viral Hepat 2015; 22: (Suppl. S1), 26-45.

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.

Gane E, Kershenobich D, Seguin-Devaux C, et al. Strategies to manage hepatitis C virus (HCV) infection disease burden - volume 2. J Viral Hepat 2015; 22: (Suppl. S1), 46-73.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.

Dore GJ, Ward J, Thursz M. Hepatitis C disease burden and strategies to manage the burden. J Viral Hepat 2014; 21: (Suppl. 1), 1-4.

Chronic hepatitis C virus (HCV) infection leads to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The recent Global Burden of Disease project estimated that in 2010 among 170 million people living with chronic HCV, an estimated 483 100 people died from HCV-related liver failure or HCC. The last two decades has seen progressive improvements in treatment of HCV infection with the most recent therapies offering simple, tolerable, short-duration therapy with extremely high efficacy. The development of public health strategies addressing emerging epidemics requires sound epidemiological data. This study covers epidemiological data collection, detailed expert opinion input and country-specific mathematical modelling of the HCV epidemic and potential impact of improved HCV treatment strategies in 16 countries. The analysis demonstrates that the HCV epidemics vary considerably in terms of age distribution of the infected population across countries. In addition, the burden of advanced liver disease varies widely. This burden is dependent upon factors including chronic HCV prevalence, age distribution (and duration of infection) of those infected, prevalence of cofactors for disease progression (particularly heavy alcohol intake) and uptake and success of therapeutic intervention. Introduction of new therapies with assumed sustained virological response (SVR) rate of >90% will have a modest impact on projected advanced liver disease burden. A combination of enhanced treatment efficacy and improved treatment uptake will have a greater impact on population-level disease burden. However public health advocacy and both public and private sector investment in the HCV response are required to demonstrate significant reduction in HCV disease burden.

Bruggmann P, Berg T, Ovrehus ALH, et al. Historical epidemiology of hepatitis C virus (HCV) in selected countries. J Viral Hepat 2014; 21: (Suppl. 1), 5-33.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Razavi H, Waked I, Sarrazin C, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014; 21: (Suppl. 1), 34-59.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modeling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013–2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today’s treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Wedemeyer H, Duberg AS, Buti M, et al. Strategies to manage hepatitis C virus (HCV) disease burden. J Viral Hepat 2014; 21: (Suppl. 1), 60-89.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Gane E, Stedman C, Brunton C, et al. Impact of improved treatment on disease burden of chronic hepatitis C in New Zealand. NZ Med J 2014; 127: 61-74.

Background Chronic hepatitis C is an important cause of liver failure, liver cancer and liver-related deaths in New Zealand. Although these complications can be prevented by HCV eradication, current treatment uptake is <1% per annum. We describe the burden of HCV infection and estimate the effect of four different treatment strategies to reduce HCV-related morbidity and mortality. Methods Baseline model parameters were based upon literature review and expert consensus, focusing on New Zealand data. Four scenarios were modelled: Scenario 1 estimated the impact of increased treatment efficacy, while Scenario 2 estimated the effect of increased treatment efficacy and gradual increases in numbers treated. Scenarios 3 and 4 estimated the impact of deferred introduction of new DAAs for either 1 or 2 years. Results Prevalence of HCV infection peaked in 2010 (50,480 cases). Peak prevalence of cirrhosis and HCC will occur after 2030. Scenario 2 resulted in sizeable decreases in HCV-related morbidity and mortality. The impact of Scenario 1 was smaller. Deferring funding for new DAA treatments for a further 1 or 2 years resulted in an 18-36% increase in liver-related deaths in 2030. Conclusions While prevalence of chronic HCV infection may have peaked, disease burden continues to grow. Increased treatment uptake and efficacy combined with efforts to reduce disease transmission, will help prevent advanced liver disease and deaths.

Duberg AS, Blach S, Falconer K, et al. The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment stratagies. Scandinavian Journal of Gastroenterology 2014.

Objective. Recently, new highly effective direct-acting antivirals (DAAs) against hepatitis C virus (HCV) were introduced. Whether these will alleviate the anticipated increase of liver disease burden in Sweden is unknown, partly because high costs may restrict the use. The objectives were to model the HCV epidemic in Sweden, the burden of disease, and the potential impact of different treatment strategies. Material and methods. HCV disease progression was modeled to 2030. Scenarios were simulated using new DAAs with sustained annual treatment rate (n = 1130), reduced treatment rate (n = 380) to maintain budget, and increased treatment rates (n = 1430 or 2260) to reduce HCV infections. Results. With today’s triple therapies, the estimated number of serious liver complications and death are expected to peak in 2021. Using new DAAs among F0–F4 patients, an unchanged annual treatment rate can reduce the number of HCV infections by 10% by 2030; however, hepatocellular carcinoma (HCC) and mortality will remain unchanged. By reducing to 380 treatments annually and focusing on patients with advanced fibrosis (F3–F4), serious complications will remain constant but the total number of HCV infections will increase. By doubling the number of DAA treatments, HCC-incidence and liver-related deaths would decrease by 65–70% by 2030. Conclusion. Mortality and HCC can be reduced with new DAAs and sustained treatment uptake when restricted to F2–F4 patients, or with increased uptake in F0–F4 patients. Treatment restrictions to limit cost may reduce the positive effects and increase the burden of HCV infection. These results may be important for the future strategies of HCV management.

Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal of Hepatology 2014; 61: S45-S57.

The treatment of chronic hepatitis C virus (HCV) infection has the potential to change significantly over the next few years as therapeutic regimens are rapidly evolving. However, the burden of chronic infection has not been quantified at the global level using the most recent data. Updated estimates of HCV prevalence, viremia and genotypes are critical for developing strategies to manage or eliminate HCV infection. To achieve this, a comprehensive literature search was conducted for anti-HCV prevalence, viraemic prevalence and genotypes for all countries. Studies were included based on how well they could be extrapolated to the general population, sample size and the age of the study. Available country estimates were used to develop regional and global estimates. Eighty-seven countries reported anti-HCV prevalence, while HCV viraemic rates were available for fifty-four countries. Total global viraemic HCV infections were estimated at 80 (64–103) million infections. Genotype distribution was available for ninety-eight countries. Globally, genotype 1 (G1) was the most common (46%), followed by G3 (22%), G2 (13%), and G4 (13%). In conclusion, the total number of HCV infections reported here are lower than previous estimates. The exclusion of data from earlier studies conducted at the peak of the HCV epidemic, along with adjustments for reduced prevalence among children, are likely contributors. The results highlight the need for more robust surveillance studies to quantify the HCV disease burden more accurately.

Myers R, Krajden M, Bilodeau M, et al. Burden of disease and cost of chronic hepatitis C virus infection in Canada. Can J Gastroenterol Hepatol 2014; 28: 243-50.

Background: Chronic infection with hepatitis C virus (HCV) is a major cause of cirrhosis, hepatocellular carcinoma and liver transplantation. Objective: To estimate the burden of HCV-related disease and costs from a Canadian perspective. Methods: Using a system dynamic framework, the authors quantified the HCV-infected population, disease progression and costs in Canada between 1950 and 2035. Specifically, 36 hypothetical, age and sex-defined cohorts were tracked to define HCV prevalence, complications and direct medical costs (excluding the cost of antivirals). Model assumptions and costs were extracted from the literature with an emphasis on Canadian data. No incremental increase in antiviral treatment over current levels was assumed, despite the future availability of potent antivirals. Results: The estimated prevalence of viremic hepatitis C cases peaked in 2003 at 260,000 individuals (uncertainty interval 192,460 to 319,880), reached 251,990 (uncertainty interval 177,890 to 314,800) by 2013 and is expected to decline to 188,190 (uncertainty interval 124,330 to 247,200) in 2035. However, the prevalence of advanced liver disease is increasing. The peak annual number of patients with compensated cirrhosis (n=36,210), decompensated cirrhosis (n=3380), hepatocellular carcinoma (n=2220) and liver-related deaths (n=1880) are expected to occur between 2031 and 2035. During this interval, an estimated 32,460 HCV-infected individuals will die of liver-related causes. Total health care costs associated with HCV (excluding treatment) are expected to increase by 60% from 2013 until the peak in 2032, with the majority attributable to cirrhosis and its complications (81% in 2032 versus 56% in 2013). The lifetime cost for an individual with HCV infection in 2013 was estimated to be $64,694. Conclusions: Although the prevalence of HCV in Canada is decreasing, cases of advanced liver disease and health care costs continue to rise. These results will facilitate disease forecasting, resource planning and the development of rational management strategies for HCV in Canada.

Sievert W, Razavi H, Estes C, et al. Enhanced antiviral treatment efficacy and uptake in preventing the rising burden of hepatitis C-related liver disease and costs in Australia. Journal of Gastroenterology and Hepatology 2014; 29: 1-9.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is an important cause of advanced liver disease and liver-related deaths in Australia. Our aim was to describe the burden of HCV infection and consider treatment strategies to reduce HCV-related morbidity and mortality. METHODS: Baseline model parameters were based upon literature review and expert consensus with a focus on Australian data. Three treatment scenarios based on anticipated introduction of improved direct-acting antiviral regimens were considered to reduce HCV disease burden. Scenario 1 evaluated the impact of increased treatment efficacy alone (to 80-90% by 2016). Scenario 2 evaluated increased efficacy and increased treatment uptake (2550 to 13,500 by 2018) without treatment restriction, while Scenario 3 considered the same increases with treatment limited to ≥ F3 during 2015-2017. RESULTS: In 2013, there were an estimated 233,490 people with chronic HCV infection: 13,850 with cirrhosis, 590 with hepatocellular carcinoma (HCC) and 530 liver-related deaths. If the current HCV treatment setting is unchanged, threefold increases in the number of people with cirrhosis, HCC, and liver disease deaths will be seen by 2030. Scenario 1 resulted in modest impacts on disease burden (4% decrease in HCC, decompensated cirrhosis, and liver deaths) and costs. Scenario 3 had the greatest impact on disease burden (approximately 50% decrease in HCC, decompensated cirrhosis, and liver deaths) and costs, while Scenario 2 had slightly lesser impact. CONCLUSIONS: Considerable increases in the burden of HCV-related advanced liver disease and its complications will be seen in Australia under current treatment levels and outcomes. Introduction of improved direct-acting antiviral regimens with enhanced efficacy at current treatment levels will lead to limited impacts on this disease burden. A combination of increased treatment efficacy and greater uptake is required to achieve major reductions in advanced liver disease and related costs.

Cramp M, Rosenberg W, Ryder S, et al. Modelling the impact of improving screening and treatment of chronic hepatitis C virus infection on future hepatocellular carcinoma rates and liver-related mortality. BMC Gastroenterology 2014.

Background: The societal, clinical and economic burden imposed by the complications of chronic hepatitis C virus (HCV) infection - including cirrhosis and hepatocellular carcinoma (HCC) - is expected to increase over the coming decades. However, new therapies may improve sustained virological response (SVR) rates and shorten treatment duration. This study aimed to estimate the future burden of HCV related disease in England if current management strategies remain the same and the impact of increasing diagnosis and treatment of HCV as new therapies become available. Methods: A previously published model was adapted for England using published literature and government reports, and validated through an iterative process of three meetings of HCV experts. The impact of increasing diagnosis and treatment of HCV as new therapies become available was modeled and compared to the base-case scenario of continuing current management strategies. To assess the ‘best case’ clinical benefit of new therapies, the number of patients treated was increased by a total of 115% by 2018. Results: In the base-case scenario, total viraemic (HCV RNA-positive) cases of HCV in England will decrease from 144,000 in 2013 to 76,300 in 2030. However, due to the slow progression of chronic HCV, the number of individuals with cirrhosis, decompensated cirrhosis and HCC will continue to increase over this period. The model suggests that the ‘best case’ substantially reduces HCV-related hepatic disease and HCV-related liver mortality by 2020 compared to the base-case scenario. The number of HCV-related HCC cases would decrease 50% by 2020 and the number progressing from infection to decompensated cirrhosis would decline by 65%. Therefore, compared to projections of current practices, increasing treatment numbers by 115% by 2018 would reduce HCV-related mortality by 50% by 2020. Conclusions: This analysis suggests that with current treatment practices the number of patients developing HCV-related cirrhosis, decompensated cirrhosis and HCC will increase substantially, with HCV-related liver deaths likely to double by 2030. However, increasing diagnosis and treatment rates could optimise the reduction in the burden of disease produced by the new therapies, potentially halving HCV-related liver mortality and HCV-related HCC by 2020.

Flisiak R, Halota W, Krzysztof T, et al. Forecasting the disease burden of chronic hepatitis C virus in Poland. Eur J Gastroenterol Hepatol 2014; 27: 70-6.

BACKGROUND AND AIMS: Chronic hepatitis C virus infection is prevalent among 200,000 individuals in Poland; however, few are aware of their condition (30,000 diagnosed) and even fewer are treated (2490 in 2014). This analysis projected future disease burden and developed two treatment scenarios to control or eliminate hepatitis C virus-related disease in Poland. METHODS: Using a modeling approach, the infected population and future disease progression were quantified. Baseline variables included viremic prevalence, age and sex, diagnosis rate, treatment rate, disease progression, and sustained virologic response rates. Data were collected from the literature and through expert interviews. RESULTS: The number of prevalent hepatitis C virus infections is projected to decrease (5%) by 2030. However, the numbers of individuals with compensated and decompensated cirrhosis, and hepatocellular carcinoma are estimated to increase by 40, 55, and 60%, respectively. By increasing sustained virologic response rates to 95% from 2015 onward, and the number of treated cases (from 2490 to 5000), the number of individuals with cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma is projected to remain constant until 2030. A strategy to eliminate chronic hepatitis C virus infection was also considered. To reduce total infections by 90% and mortality by 80%, treatment was increased to 15,000 patients annually. This scenario required the diagnosis of 15,000 new cases (compared with 3000 today). CONCLUSION: A marked reduction in hepatitis C virus-related disease burden is possible, with increased diagnosis and treatment. The results could inform the development of effective disease management in Poland.

Waked I, Doss W, El-Sayed MH, et al. The current and future disease burden of chronic hepatitis C virus infection in Egypt. Arab J Gastroenterol 2014.

Vandijck D, Starkel P. Perspective editorial: Innovative strategies for hepatitis C in Belgium integrating treatment efficacy, public disease burden, and healtcare costs. Acta Gastroenterol Belg 2014; 77: 274-6.

Van Damme P, Laleman W, Starkel P, et al. Hepatitis C Epidemiology in Belgium. Acta Gastroenterol Belg 2014; 77: 277-9.

BACKGROUND: The burden of hepatitis C virus (HCV) infection is significant and is increasing with the aging population. The results of a modeling study that included Belgium, along with many other countries, was published in April 2014. An in depth discussion surrounding the epidemiology of HCV in Belgium will be presented here. METHODS: A systematic literature review was conducted to assess the historical and current clinical burden of HCV in Belgium. Two expert panels were convened to discuss the strengths and limitations surrounding the available data and to generate consensus regarding the best estimates for total number of HCV cases, number of cases diagnosed, and the number of patients treated and cured, including potential HCV control strategies. RESULTS: Although no national studies exist, there were an estimated 70,000 (10,000-91,000) viremic HCV infections in 1994. By 2010 there were an estimated 22,900 individuals diagnosed with viremic HCV, and in 2011 approximately 710 patients were treated annually. An estimated 13% of liver transplants were attributable to HCV in 2011. Genotype 1 predominated (59%), followed by genotypes 3 (19%) and 4 (14%). CONCLUSIONS: Estimates of HCV prevalence, diagnosed cases and liver transplants due to HCV were available through published studies. However these publications were subject to bias and were occasionally outdated. Improved estimates of HCV prevalence would be useful for informing treatment, prevention and policy efforts in Belgium.

Starkel P, Vandijck D, Laleman W, et al. The Disease Burden of Hepatitis C in Belgium: development of a realistic disease control strategy. Acta Gastroenterol Belg 2014; 77: 280-4.

BACKGROUND: Novel direct antiviral agents (DAAs) will become available soon with higher sustained viral response (SVR), fewer side-effects and higher compliance. Our aim was to evaluate different realistic strategies to control the projected increase in HCV-related disease burden in Belgium. METHODS: Based on literature review, expert opinions and historical assumptions, HCV-disease progression and mortality in Belgium was modeled to 2030. Strategies exploring the impact of increased treatment, treatment delay, and treatment restrictions were developed. RESULTS: Although the overall HCV prevalence is decreasing in Belgium, the burden of advanced stage HCV, including cirrhosis and hepatocellular carcinoma (HCC), is expected to increase under current treatment and cure rates. By increasing SVR to 90% from 2016 onward and the number of treated cases (from 710 to 2,050), in 2030 the cases with cirrhosis, decompensated cirrhosis and HCC would be significantly lower than in 2013. This strategy was found most efficient when applied to F2-F4 cases. To obtain comparable outcomes with F0-F4 cases, 3,490 patients should be treated. A two year delayed access to the DAAs increased HCV related morbidity and mortality by 15% relative to our strategy. CONCLUSIONS: Considering the evolving burden of HCV disease and the need for efficacious usage of healthcare resources, primary application of new DAAs in Belgium should focus on patients with significant and advanced fibrosis (F2-F4), providing these new drugs without delay upon availability and increasing access to therapy

Vandijck D, Moreno C, Starkel P, et al. Current and future health and economic impact of hepatitis C in Belgium. Acta Gastroenterol Belg 2014; 77: 285-90.

BACKGROUND AND STUDY AIMS: Chronic hepatitis C virus (HCV) infection is a serious global health problem affecting 150 million individuals worldwide. Although infection rates are decreasing, an aging population with progressing disease is expected to result in increased burden of advanced stage disease with high associated costs. This analysis describes the current and projected future economic impact of HCV sequelae in Belgium. METHODS: A previously described and validated model was populated with Belgian inputs and calibrated to project the current and future health and economic burden of HCV. Monte Carlo and sensitivity analyses were run to quantify uncertainty. All estimates exclude the cost of antiviral therapy. RESULTS: Costs associated with HCV were projected to peak in 2026 at Euro126M (Euro30M-Euro257M), while decompensated cirrhosis and hepatocellular carcinoma costs were projected to increase until 2031 and 2034. The projected 2014-2030 cumulative cost of HCV under current conditions was Euro1,850M. Scenarios to reduce the burden of HCV could result in Euro70M-Euro400M in cumulative cost savings. Starting treatment (1,000 patients) in 2015 could result in Euro150M cost savings. The lifetime cost of HCV increases with life expectancy, with highest future costs projected among young females with early stage disease. CONCLUSIONS: The economic burden of HCV and advanced stage disease were projected to further increase. Cost reductions are possible with timely interventions aimed at minimizing the health burden of advanced stage disease.

Mennini FS, Marcellusi A, Andreoni M, et al. Health policy model: long-term predictive results associated with the management of hepatitis C virus-induced diseases in Italy. Clinicoecon Outcomes Res. 2014 Jun 19;6:303-10.

Background: At present, there are no specific nationwide epidemiological studies representing the whole Italian population. This study is aimed at describing the epidemiological and economic burden that HCV will generate in the next few years in Italy. Furthermore, the impact that future anti-HCV treatments may have on the burden of disease was considered. This analysis was developed for the period 2012–2030 from the perspective of the Italian National Health Service (NHS). Methods: A published system dynamic model was adapted for Italy in order to quantify the HCV infected population in terms of disease progression and the associated costs from 1950 to 2030. The model structure was based on transition probabilities reflecting the natural history of the disease. In order to estimate the efficacy of current anti-HCV treatment strategies for genotypes 1 and 4, the sustained virological response (SVR) rate in registration clinical trials for both boceprevir and telaprevir was estimated. It was assumed that the efficacy for patients treated with peginterferon + ribavirin was equal to the placebo arm of a randomized clinical trial (RCT) relating to boceprevir and telaprevir. For genotypes 2/3 patients it was assumed that treatment efficacy with dual therapy was equal to a SVR rate from the literature. According to the aim of this study, only direct health care costs (hospital admissions, drugs, treatment, and care of patients) incurred by the Italian NHS have been included in the model. Costs have been extrapolated using the published scientific literature available in Italy and actualized with the 2012 ISTAT (Istituto Nazionale di Statistica) Price Index system for monetary revaluation. Three different scenarios were assumed in order to evaluate the impact of future anti-HCV treatments on the burden of disease. Results: Overall, in Italy, 1.2 million infected subjects were estimated in 2012. Of these, about 211,000 patients were diagnosed, while only about 11,800 subjects were actually being treated with anti-HCV drugs. A reduction of health care costs is associated with a prevalence decrease. Indeed, once the spending peak is reached during this decade (about €527 million), the model predicts a cost reduction in the following 18 years. In 2030, based on the more effective treatments currently available, the direct health care cost associated with the management of HCV patients may reach €346 million (−34.3% compared to 2012). The first scenario (new treatment in 2015 with SVR =90% and same number of treated patients) was associated with a significant reduction in HCV-induced clinical consequences (prevalence =−3%) and a decrease in direct health care expenses, corresponding to €11.1 million. The second scenario (increase in treated patients to 12,790) produced an incremental cost reduction of €7.3 million, reaching a net decrease equal to €18.4 million. In the third scenario (treated patients =16,770), a higher net direct health care cost decrease versus the base-case (€44.0 million) was estimated. Conclusion: Our model showed that the introduction of new treatments that are more effective could result in a quasi-eradication of HCV, with a very strong reduction in prevalence.

Murray CJ, Ortblad K, Guinovart C, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384: 1005-70.

Background The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. Methods To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010–13) of incidence, drug resistance, and coverage of insecticide-treated bed nets. Findings Globally in 2013, there were 1•8 million new HIV infections (95% uncertainty interval 1•7 million to 2•1 million), 29•2 million prevalent HIV cases (28•1 to 31•7), and 1•3 million HIV deaths (1•3 to 1•5). At the peak of the epidemic in 2005, HIV caused 1•7 million deaths (1•6 million to 1•9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19•1 million life-years (16•6 million to 21•5 million) have been saved, 70•3% (65•4 to 76•1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7•5 million (7•4 million to 7•7 million), prevalence was 11•9 million (11•6 million to 12•2 million), and number of deaths was 1•4 million (1•3 million to 1•5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7•1 million (6•9 million to 7•3 million), prevalence was 11•2 million (10•8 million to 11•6 million), and number of deaths was 1•3 million (1•2 million to 1•4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64•0% of cases (63•6 to 64•3) and 64•7% of deaths (60•8 to 70•3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1•2 million deaths (1•1 million to 1•4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31•5% (15•7 to 44•1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. Interpretation Our estimates of the number of people living with HIV are 18•7% smaller than UNAIDS’s estimates in 2012. The number of people living with malaria is larger than estimated by WHO. Incidence rates for HIV, tuberculosis, and malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action

Razavi H, Bruggmann P, Wedemeyer H, and Dore G. Response to letter to the editor: Strategies to reduce HCV disease burden and HCV transmission need different models, as what works for end-stage liver disease may not work for HCV prevalence: a comment on the results presented in JVH Special Issue. J Viral Hepat 2014; 21: e169-e170.

Afdhal NH, Zeuzem S, Schooley RT, et al. The new paradigm of hepatitis C therapy: integration of oral therapies into best practices. J Viral Hepat 2013; 20: 745-60.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.

Deelder W, Eustance J, Pingali P et al. Hepatitis C medicines and diagnostics in the context of HIV/HCV co-infection: A scoping report. UNITAID; 2013 Oct 1.

Murray CJ, Abraham J, Ali MK, et al. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA 2013; 310: 591-608.

IMPORTANCE Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.

Razavi H, Elkhoury AC, Elbasha E, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology 2013; 57: 2164-70.

Hepatitis C virus (HCV) infection is a leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation. A better understanding of HCV disease progression and the associated cost can help the medical community manage HCV and develop treatment strategies in light of the emergence of several potent anti-HCV therapies. A system dynamic model with 36 cohorts was used to provide maximum flexibility and improved forecasting. New infections incidence of 16,020 (95% confidence interval, 13,510-19,510) was estimated in 2010. HCV viremic prevalence peaked in 1994 at 3.3 (2.8-4.0) million, but it is expected to decline by two-thirds by 2030. The prevalence of more advanced liver disease, however, is expected to increase, as well as the total cost associated with chronic HCV infection. Today, the total cost is estimated at $6.5 ($4.3-$8.4) billion and it will peak in 2024 at $9.1 ($6.4-$13.3) billion. The lifetime cost of an individual infected with HCV in 2011 was estimated at $64,490. However, this cost is significantly higher among individuals with a longer life expectancy. Conclusion: This analysis demonstrates that US HCV prevalence is in decline due to a lower incidence of infections. However, the prevalence of advanced liver disease will continue to increase as well as the corresponding healthcare costs. Lifetime healthcare costs for an HCV-infected person are significantly higher than for non-infected persons. In addition, it is possible to substantially reduce HCV infection through active management

Hamoudi W, Ali SA, Abdallat M, Estes CR, Razavi HA. HCV infection prevalence in a population recruited at health centers in Jordan. J Epidemiol Glob Health 2013; 3: 67-71.

Background Jordan lacks statistical data regarding prevalence of HCV. Aim To determine the prevalence of HCV in selected areas of Jordan (north, middle and south of Jordan). Methods A random sample of 700 patients attending health centers was used to determine HCV prevalence. ELISA testing was used to determine HCV-Ab positive cases, which were confirmed by PCR testing. Results and conclusion The study concluded that the prevalence of HCV infection in the population recruited from different health centers in Jordan is relatively low and estimates a prevalence of 0.42% among all age groups and 0.56% among those aged >15 years old.

Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2013; 380: 2197-223.

Background Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. Methods We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause specific mortality, prevalence, and disability weights. Findings Global DALYs remained stable from 1990 (2•503 billion) to 2010 (2•490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. Interpretation Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2013; 380: 2224-60.

Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7•0% [95% uncertainty interval 6•2–7•7] of global DALYs), tobacco smoking including second-hand smoke (6•3% [5•5–7•0]), and alcohol use (5•5% [5•0–5•9]). In 1990, the leading risks were childhood underweight (7•9% [6•8–9•4]), household air pollution from solid fuels (HAP; 7•0% [5•6–8•3]), and tobacco smoking including second-hand smoke (6•1% [5•4–6•8]). Dietary risk factors and physical inactivity collectively accounted for 10•0% (95% UI 9•2–10•8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0•9% (0•4–1•6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.

Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163-96.

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient –0•37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world.

El Khoury AC, Wallace C, Klimack WK, Razavi H. Economic burden of hepatitis C-associated diseases: Europe, Asia Pacific, and the Americas. J Med Econ 2012; 15: 887-96.

Background: Globally, hepatitis C virus (HCV) infects ∼3% of the population. The objective of this study was to review published work and determine the direct medical costs for diseases associated with HCV infection globally, with the exception of the US. Methods: A systematic literature search was conducted to identify studies reporting the costs of hepatitis C sequelae between January 1990 and January 2011. Over 400 references were identified, of which 45 were pertinent. The costs were compiled, converted to US dollars, and adjusted to 2010 costs using the medical component of the consumer price index. Results: The median cost of liver transplants was estimated at $139,070 ($15,430–$443,700), refractory ascites at $16,740 ($8990–$35,940), hepatocellular carcinoma (HCC) at $15,310 ($3370–$84,710), decompensated cirrhosis at $14,660 ($3810–$48,360), variceal hemorrhage at $12,190 ($3550–$46,120), hepatic encephalopathy at $9180 ($5370–$50,120), diuretic sensitive ascites at $3400 ($1320–$7470), compensated cirrhosis at $820 ($50–$2890), and chronic hepatitis C at $280 ($90–$1860). The variation among studies was mainly due to the methodology used to assess cost, local cost and government reimbursement, and country-specific treatment protocols. Limitations: All costs were adjusted to 2010 US dollars using the US medical component of the consumer price index (CPI) which may not reflect the change in medical costs in other countries. In addition, the costs, in the local currency were converted to US dollars in the year of the study. However, medical expenses may not vary with exchange rate, leading to artificial variations. Finally, there was no assessment of the quality of individual studies, which resulted in the same weighting to all studies. Conclusions: Hepatitis C imposes a high economic burden globally. Knowing the burden of HCV sequelae is useful for policy decisions as well as serving as a basis for determining the value of HCV screening and treatment.

El Khoury AC, Wallace C, Klimack WK, Razavi H. Economic burden of hepatitis C-associated diseases in the United States. J Viral Hepat 2012; 19: 153-60.

There are approximately 100 drugs in development to treat hepatitis C. Over the next decade, a number of new therapies will become available. A good understanding of the cost of hepatitis C sequelae is important for assessing the value of new treatments. The objective of this study was to assess the economic burden data sources for hepatitis C in the United States. A systematic literature search was conducted to identify studies reporting the costs of hepatitis C sequelae in the United States. Over 400 references were identified, of which 50 were pertinent. The costs were compiled and adjusted to 2010 constant US dollars using the medical component of the consumer price index (CPI). The cost of liver transplants was estimated at $201 110 ($178 760–$223 460), hepatocellular carcinoma (HCC) at $23 755–$44 200, variceal haemorrhage at $25 595, compensated cirrhosis at $585–$1110, refractory ascites at $24 755, hepatic encephalopathy at $16 430, sensitive ascites at $2450, moderate chronic hepatitis C at $155, and mild chronic hepatitis C at $145 per year per person. All studies were traced back to a handful of publications in the 1990s, which have provided the basis for all sequelae-based cost estimates to date. Hepatitis C imposes a high economic burden. Most cost analysis is more than 10 years old, and more research is required to update the sequelae costs associated with HCV infection.

Negro F, Alberti A. The global health burden of hepatitis C virus infection. Liver Int 2011; 31 Suppl 2: 1-3.

Kershenobich D, Razavi HA, Cooper CL, et al. Applying a system approach to forecast the total hepatitis C virus-infected population size: Model validation using US data. Liver Int 2011; 31 Suppl 2: 4-17.

Background: Hepatitis C virus (HCV) infection is associated with chronic progressive liver disease. Its global epidemiology is still not well ascertained and its impact will be confronted with a higher burden in the next decade. Aim: The goal of this study was to develop a tool that can be used to predict the future prevalence of the disease in different countries and, more importantly, to understand the cause and effect relationship between the key assumptions and future trends. Methods: A system approach was used to build a simulation model where each population was modeled with the appropriate inflows and outflows. Sensitivity analysis was used to identify the key drivers of future prevalence. Results: The total HCV-infected population in the US was estimated to decline 24% from 3.15 million in 2005 to 2.47 million in 2021, while disease burden will increase as the remaining infected population ages. During the same period, the mortality rate was forecasted to increase from 2.1 to 3.1%. The diagnosed population was 50% of the total infections, while less than 2% of the total infections were treated. Conclusion: We have created a framework to evaluate the HCV-infected populations in countries around the world. This model may help assess the impact of policies to meet the challenges predicted by the evolution of HCV infection and disease. This prediction tool may help to target new public health strategies.

Kershenobich D, Razavi HA, Sanchez-Avila JF, et al. Trends and projections of hepatitis C virus epidemiology in Latin America. Liver Int 2011; 31 Suppl 2: 18-29.

Background and aim: The purpose of the present investigation is to provide an analysis of previous works on the epidemiology of the hepatitis C virus (HCV) infection from six countries throughout Latin America, to forecast the future HCV prevalence trends in Argentina, Brazil, Mexico and Puerto Rico, and to outline deficiencies in available data, highlighting the need for further research. Methods: Data references were identified through indexed journals and non-indexed sources. Overall, 1080 articles were reviewed and 150 were selected based on their relevance to this work. When multiple data sources were available for a key assumption, a systematic process using multi-objective decision analysis (MODA) was used to select the most appropriate sources. When data were missing, analogues were used. Data from other countries with similar risk factors and/or population compositions were used as a proxy to help predict the future trends in prevalence. Results: The review indicates that the dominant genotype is type 1. HCV prevalence in the analysed countries ranges from 1 to 2.3%. The Latin American countries have been very proactive in screening their blood supplies, thus minimizing the risk of transmission through transfusion. This suggests that other risk factors are set to play a major role in continued new infections. The number of diagnosed and treated patients is low, thereby increasing the burden of complications such as liver cirrhosis or hepatocellular carcinoma. The HCV prevalence, according to our modelling is steady or increasing and the number of infected individuals will increase. Conclusions: The results herein reported should provide a foundation for informed planning efforts to tackle hepatitis.

Cornberg M, Razavi HA, Alberti A, et al. A systematic review of hepatitis C virus epidemiology in Europe, Canada and Israel. Liver Int 2011; 31 Suppl 2: 30-60.

Background and Aim: Decisions on public health issues are dependent on reliable epidemiological data. A comprehensive review of the literature was used to gather country-specific data on risk factors, prevalence, number of diagnosed individuals and genotype distribution of the hepatitis C virus (HCV) infection in selected European countries, Canada and Israel. Methodology: Data references were identified through indexed journals and non-indexed sources. In this work, 13 000 articles were reviewed and 860 were selected based on their relevance. Results: Differences in prevalence were explained by local and regional variances in transmission routes or different public health measures. The lowest HCV prevalence (≤0.5%) estimates were from northern European countries and the highest (≥3%) were from Romania and rural areas in Greece, Italy and Russia. The main risk for HCV transmission in countries with well-established HCV screening programmes and lower HCV prevalence was injection drug use, which was associated with younger age at the time of infection and a higher infection rate among males. In other regions, contaminated glass syringes and nosocomial infections continue to play an important role in new infections. Immigration from endemic countries was another factor impacting the total number of infections and the genotype distribution. Approximately 70% of cases in Israel, 37% in Germany and 33% in Switzerland were not born in the country. In summary, HCV epidemiology shows a high variability across Europe, Canada and Israel. Conclusion: Despite the eradication of transmission by blood products, HCV infection continues to be one of the leading blood-borne infections in the region.

Sievert W, Altraif I, Razavi HA, et al. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int 2011; 31 Suppl 2: 61-80.

Background: The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in other regions. Aim: The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population. Methodology: Data references were identified through indexed journals and non-indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance. Results: We estimated that 49.3–64.0 million adults in Asia, Australia and Egypt are anti-HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4 was found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria. Conclusion: We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection

Posters

Callens S, De Wit S, Wyndham-Thomas C, Goffard J, Moutschen M, Meuris C, et al. Epidemiologic ‘snapshot’ of the HIV-positive population in Belgium, 2014–2016. HIV Glasgow Drug Therapy; Glasgow, Scotland 2016.(INHSU)

The Economic Impact of Treating Hepatitis C in Ethiopia: The Case for Increased Investment. Shewaye AB, Berhane R, Workneh AB, Robbins S, Razavi H. African Society for Laboratory Medicine December 2016.

Eliminating Hepatitis C in Spain: Bridging from the National Health Plan. María Buti, Jose Luis Calleja, Javier Garcia-Samaniego, Miguel Angel Serra, Javier Crespo, Manuel Romero , Miguel Angel Simon, Antonio Javier Blasco, Pablo Lazaro, Sarah Robbins, Homie Razavi. AASLD The Liver Meeting November 2016.

Razavi-Shearer D, Dalgard O, Kielland KB, Razavi H, Wüsthoff LE, Migard H. Reinfection of Hepatitis C Among People Who Inject Drugs in Norway: Opportunity for Intervention - A Modelling Study. The 5th International Symposium on Hepatitis Care for Substance Users. October 2016. (INHSU)

Razavi-Shearer D, Kielland KB, Migard H, Razavi H, Wüsthoff LE, Dalgard O. Adherence To Hepatitis C Treatment Regimen Among People Who Inject Drugs in Norway: Implications for Treatment Strategies. The 5th International Symposium on Hepatitis Care for Substance Users. October 2016. (INHSU)

Razavi-Shearer D, Dalgard O, Migard H, Razavi H, Wüsthoff LE, Kielland KB. Aggressive Treatment OF Hepatitis C in People Who Inject Drugs in Norway: An Integral Step to Eradicate the Infection in this Population. The 5th International Symposium on Hepatitis Care for Substance Users. October 2016. (INHSU)

Bourgeois S, Brixko C, Blach S, et al. The modeled impact of improved Hepatitis C Virus (HCV) treatment strategies on HCV prevalence among people who inject drugs (PWIDs) in Belgium. The 4th International Symposium on Hepatitis Care in Substance Users. October 7-9, 2015. (INHSU 2015)

Bruggmann P, Blach S, Deltenre P, et al. Hepatitis C virus (HCV) prevalence among people who inject drugs (PWIDs) in Switzerland.The 4th International Symposium on Hepatitis Care in Substance Users. October 7-9, 2015. (INHSU 2015)

Matheï C, Bourgeois S, Brixko C, et al. The modeled impact of improved Hepatitis C Virus (HCV) treatment strategies on HCV prevalence among people who inject drugs (PWIDs) in Belgium. The 66th Annual Meeting of the American Association for the Study of Liver Diseases. November 13-17, 2015. (AASLD 2015)

Negro F, Bruggmann P, Blach S, et al. Hepatitis C virus (HCV) prevalence among people who inject drugs (PWIDs) in Switzerland.The 66th Annual Meeting of the American Association for the Study of Liver Diseases. November 13-17, 2015. (AASLD 2015)

Hamid S , Jafri SM , Qureshi H , Chaudhry AA , Abbas Z , Alam A , Baqir A , Farooqi JI , Memon MS , Nawaz AA , Razavi H , Razavi-Shearer DM , Salamat A , Siddiq M , Siddiqi A , Tayyab G , Uddin M , Yusuf A , Zuberi BF, and Khan AG. Can Hepatitis C be eliminated from a high disease burden country like Pakistan? 50th Annual Meeting of the European Association for the Study of the Liver. April 22-26, 2015. (EASL 2015)

Chulanov V, Sagalova O, Blokhina N, Mamonova N, Nurmukhametova E, Pimenov N, Rakhmanova A, Razavi H, Razavi-Shearer K, Shevaldin A, Chesnokov E, Sokolov S, Strebkova E, Znoiko O, and Shestakova I. Forecasting the disease burden of chronic hepatitis C in Russia. 50th Annual Meeting of the European Association for the Study of the Liver. April 22-26, 2015. (EASL 2015)

El-Sayed M, Razavi H. Global estimate of HCV infection in the pediatric and adolescent population. 50th Annual Meeting of the European Association for the Study of the Liver. April 22-26, 2015. (EASL 2015)

Øvrehus A, Blach S, Christensen P, Gerstoft J, Weis N, Krarup H, Clausen M, and Razavi H. Impact of prioritizing treatment in a high resource setting – minimizing the burden of HCV related disease in 15 years. 50th Annual Meeting of the European Association for the Study of the Liver. April 22-26, 2015. (EASL 2015)

Seguin-Devaux C, Arendt V, Blach S, Hoffmann P, Razavi H, Staub T, Struck D, and Mossong J. Birth cohort distribution and screening of viremic HCV infections in Luxembourg. 50th Annual Meeting of the European Association for the Study of the Liver. April 22-26, 2015. (EASL 2015)

Sypsa V, Gountas Ι, Papatheodoridis G, Souliotis K, Razavi H, and Hatzakis A. Estimating the number of chronic hepatitis C patients in need of treatment and projecting the disease burden during 2015-2030 under the interferon-free treatment regimens in Greece. 50th Annual Meeting of the European Association for the Study of the Liver. April 22-26, 2015. (EASL 2015)

Razavi H, Estes C, Hindman S, Razavi-Shearer K, Gower E. The Global Burden of Viremic HCV Infection. Hepatology 2014; 60: 1488. (AASLD 2014)

Ridruejo E, Daruich JR, Estes C, Gadano AC, Razavi H, Silva MO, Villamil FG, Bessone F. Hepatitis C Virus (HCV) Infection in Argentina: Burden of Chronic Disease. Hepatology 2014; 60: 1517. (AASLD 2014)

Puri P, Anand AC, Saraswat VA, Acharya SK, Sarin SK, Dhiman R, Aggarwal R, Singh SP, Amarapurkar DN, Arora A, Chhabra M, Chetri K, Choudhuri G, Chowdhury A, Dixit VK, Duseja AK, Blach S, Jain AK, Kapoor D, Kar P, Koshy A, Kumar A, Madan K, Misra SP, Prasad MV, Nagral A, Puri AS, Ramachandran J, Razavi H, Saigal S, Shah SR, Sharma PK, Sood A, Thareja S, Wadhawan M. Disease Burden of Chronic Hepatitis C Virus (HCV) Infection in India. Hepatology 2014; 60: 1536. (AASLD 2014)

Estes C, Bergin C, Houlihan D, Razavi H, Razavi-Shearer K, Thornton L, Norris S. Disease Burden of Chronic Hepatitis C Virus (HCV) Infection in Ireland. Hepatology 2014; 60: 1514. (AASLD 2014)

Gane E, Brunton C, Estes C, Henderson C, Hornell J, Radke S, Razavi H, Stedman C. Hepatitis C Virus (HCV) Infection in New Zealand: Burden of Chronic Disease. Hepatology 2014; 60: 1587. (AASLD 2014)

Flisiak R, Halota W, Tomasiewicz K, Kostrzewska K, Razavi H, Gower E. The Disease Burden of Chronic Hepatitis C Virus (HCV) Infection in Poland. Hepatology 2014; 60: 1760. (AASLD 2014)

Duberg AS, Blach S, Falconer K, Kaberg M, Razavi H, Aleman S. The Impact of Different Strategies to Reduce the Burden of Chronic Hepatitis C Virus (HCV) Infection, Using New Direct Acting Antivirals in Sweden. Hepatology 2014; 60: 1763. (AASLD 2014)

Bruggmann P, Negro F, Bihl F, Blach S, Lavanchy D, Müllhaupt B, Razavi H, Semela D. Birth Cohort Distribution and Screening of Viremic HCV Infections in Switzerland. Hepatology 2014; 60: 1478. (AASLD 2014)

Semela D, Blach S, Bihl F, Bruggmann P, Lavanchy D, Negro F, Razavi H, Müllhaupt B. The impact of time on a scenario to minimize hepatitis C virus (HCV). Hepatology 2014; 60: 1484. (AASLD 2014)

Waked I, Estes C, Abdel Razek W, Zaghla H, Osman W, Abdel Kareem M, Abdelsamea E, Mehrez M, Gomaa A, Razavi H. Total Economic Burden of Hepatitis C in Egypt. AASLD Conference. November 7-11. 2014. (AASLD/EASL Special Conference 2014)

Estes C, Razavi H, Waked I. Future Economic Burden of Hepatitis C in Egypt: Impact of Treatment Strategies. AASLD Conference. November 7-11. 2014. (AASLD/EASL Special Conference 2014)

Ferreira PRA, Brandao-Mello CE, Estes C, et al. Disease Burden of Chronic Hepatitis C Virus (HCV) Infection in Brazil. Latin American Association for the Study of the Liver Congress. September 11-13, 2014. (ALEH 2014)

Dore GJ, Razavi H, Estes C, Thompson A, Zekry A, Roberts S, Sievert W. Potential impact of improved treatment on disease burden of chronic hepatitis C in Australia. The International Liver Congress. 49th Annual Meeting of the European Association for the Study of the Liver. April 9-13, 2014. (EASL 2014)

Vogel W, Gschwantler M, Hindman S, Hofer H, Stauber R, Razavi H. The disease burden of chronic hepatitis C virus (HCV) infection in Austria. The International Liver Congress. 49th Annual Meeting of the European Association for the Study of the Liver. April 9-13, 2014. (EASL 2014)

Waked I, Doss W, El-Sayed MH, Estes C, Razavi H, Shiha G, Yosry A, Esmat G. The disease burden of chronic hepatitis C virus (HCV) infection in Egypt: Future impact of varying treatment strategies. The International Liver Congress. 49th Annual Meeting of the European Association for the Study of the Liver. April 9-13, 2014. (EASL 2014)

Rosenberg WM, Cramp M, Davis M, Parkes J, Ryder S, Razavi H, Hindman S. Reducing the disease burden of chronic hepatitis C virus (HCV) in England. The International Liver Congress. 49th Annual Meeting of the European Association for the Study of the Liver. April 9-13, 2014. (EASL 2014)

Bruggmann P, Negro F, Bihl F, Hindman S, Lavanchy D, Müllhaupt B, Razavi H, Semela D. The disease burden of chronic hepatitis C virus (HCV) infection in Switzerland. The International Liver Congress. 49th Annual Meeting of the European Association for the Study of the Liver. April 9-13, 2014. (EASL 2014)

Sievert W, Razavi H, Estes C, Thompson A, Zekry A, Roberts S, Dore GJ. Potential effect of improved treatment outcomes on chronic hepatitis C virus (HCV) infection in Australia. Asian Pacific Association for the Study of the Liver Conference. March 12-15. 2014. (APASL 2014)

Calinas F, Estes C, Félix J, Giria J, Razavi H, Sarmento Castro R, Marinho RT. Impacto potencial dos novos tratamentos na progressão estimada da doença e peso da infecção pelo vírus da hepatite C (VHC) em Portugal. Congresso Português de Hepatologia 2014. February 7-8, 2014. (Congresso Portugues de Hepatologia)

Razavi H, Hindman S, Gower E, Estes C. Global Distribution of HCV Genotypes. Hepatology 2013; 58: 1288A. (AASLD 2013)

Leleu H, Razavi H, Estes C, et al. Modeling the Epidemiological Impact of Upcoming Direct Antiviral Agents in Hepatitis C Treatment. Hepatology 2013; 58: 92A-207A. (AASLD 2013)

Razavi H, Estes C, Pasini K, Levitch A. The Number of Treated HCV Infected Patients in Select Countries/Regions in 2004-2010. Hepatology 2012; 56: 191A-1144A. (AASLD 2013)

 

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