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Historical epidemiology of hepatitis C virus (HCV) in select countries
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Journal of Viral Hepatology Dec 2014
ABSTRACT
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 Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated.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.
INTRODUCTION
The epidemiology of hepatitis C virus (HCV) infection remains poorly understood in many countries. At the same time, HCV related mortality continues to increase as the infected population ages (1) and HCV related morbidity is forecasted to increase as the infected population advances to late-stage liver diseases (2-4).
In 2010, the World Health Assembly adopted resolution WHA 63.18 that recognized viral hepatitis as a global public health problem (5). By 2014, the World Health Organization adopted resolution WHA76.6 asking countries to develop comprehensive national hepatitis strategies (6). However, countries require reliable data and an understanding of the disease dynamics in order to develop robust strategies.
A number of studies have characterized HCV infection rates across different countries/regions (7-12), but they have typically focused on quantifying the anti-HCV infections. This study is a continuation of a project to quantify HCV epidemiology in countries around the world in a systematic manner.
The aim of this study was to develop consensus estimates, using the best available published and unpublished data, for the total number of viremic infections [HCV ribonucleic acid (RNA) positive], the total number of viremic diagnosed individuals, the number of viremic newly diagnosed, annual number of treated patients and the number of liver transplants attributed to HCV in each country. The countries were selected based on the availability of published data and the willingness to collaborate. Other countries are being analyzed and will be published separately.
Russia
HCV Infected Population - The estimate for prevalence in the general Russian population was derived from a general consensus of 4.1% in 2010 reported in multiple sources (8;105;106). Applying a viremic rate of 71% (107), the viremic prevalence in 2010 was estimated at 2.91%, corresponding to 4 162 000 infections. The age and gender distribution was developed using the age distribution and gender ratio of infection presented previously (108). The genotype distribution was developed using data from a regional registry of more than 40 000 patients with chronic viral hepatitis (108).
Diagnosed - Using unpublished data and an analysis of regional registries conducted by the Russian National Reference Center for Viral Hepatitis, approximately 43% of the infected population in 2012 had received anti-HCV testing (109). In 2012, 55 900 chronic individuals were newly diagnosed (unpublished data).
Treated - Using regional registries, it was estimated that 5500 patients were treated in 2011.
Liver Transplants - Liver transplant data were available through the Russian transplant society (110;111). In 2011, there were 204 liver transplants performed in Russia (110). It was estimated that 32% of liver transplants per year were attributable to HCV (112;113).
India
HCV Infected Population - The anti-HCV seroprevalence was estimated at 0.84% in 2013. This estimate was calculated using a weighted average of published estimates from non-blood donor and non-tribal population studies (30-39). An anti-HCV range of 0.5%-1.5% was chosen from a consensus document published by the HCV Taskforce of the Indian National Association for the Study of the Liver (Personal communication with P. Puri 2014). A viremic rate of 80.8% (30) was used, corresponding to 0.68% (0.40%-1.21%) viremic prevalence in 2012. A 2005 age distribution was chosen from a study of volunteer blood donors, in which seroprevalence was highest among individuals 41-50 years of age, and males were more commonly infected than females (M:F ratio - 1.64:1.00) (40).
The genotype distribution was obtained from a subtyping analysis of 398 patients (Personal communication with Samir Shah, 2014). Genotypes 3 and 1 accounted for 64% and 28% of HCV infections, respectively, with 16% (of all infections) genotype 1b. Genotype 4a accounted for the remaining 7% of infections, with <1% genotype 5.
Diagnosed - There were an estimated 408 300 previously diagnosed viremic infections by 2012. This estimate was generated using blood bank reports and linear extrapolations. The number of HCV positive blood units from 2004 and 2008 were used to estimate the number of HCV positive units in 2003, 2005-2007 and 2009-2012 (41;42). It was then assumed that for every diagnosis in blood banks, two other cases were diagnosed among physicians or hospitals. The total number of diagnosed cases from blood banks was multiplied by a factor of 2 to account for diagnoses occurring outside of the blood supply system, and adjusted for viremia using the above viremic rate. In 2012, there were an estimated 52 600 new viremic diagnoses.
Treated - IMS data were used to estimate 15 000 patients were treated annually in 2011.
Liver Transplants - Liver transplant data from 1998-2013 were extrapolated using published literature (43) and expert feedback. The first liver transplant occurred in 1998, and by 2007, a total of 343 transplants had been performed in India (43). Following 2007, the number of transplants annually began to increase rapidly, with 300 transplants in 2009 and 800-900 in 2013 (Expert consensus). An estimated 40% of transplants were attributable to HCV (44), and expert consensus suggests that approximately 50% of transplants were performed on patients from other countries. In 2011, an estimated 375 transplants were performed, with 109 (29%) attributable to HCV.
Argentina
HCV Infected Population - HCV epidemiology data are sparse in Argentina. The prevalence of anti-HCV in adults (individuals aged ≥20 years) was estimated at 1.50% based on expert consensus, with lower prevalence among younger individuals. A viremic rate of 80% was applied (16). The total viremic population in 2013 was estimated at 342 000 individuals, corresponding to viremic prevalence of 0.83%. For the age and gender distribution of the infected population, a hybrid distribution was constructed using notification data for HCV infection (17) for individuals aged 0-59 years and transplant data (18) organized by age and gender for individuals aged ≥60 years. The notified and transplanted populations were aged to the year 2013, accounting for mortality and cured patients. The genotype distribution of the prevalent population was estimated using data from a population of over 200 treated patients (19), while the distribution of G1 subtypes was based on sentinel unit data (20).
Diagnosed - Estimates of the diagnosed population were based upon data for positive blood donations from the Pan American Health Organization (12). The annual number of notifications was scaled up to account for diagnosis in other venues. There were an estimated 112 300 previously diagnosed cases in 2010 and 4900 newly diagnosed cases.
Treated - It was estimated that 200 patients annually were treated based on expert consensus and IMS data for standard units of Peg-IFN sold after adjustment to account for under-reporting.
Liver Transplants - In 2013, there were 329 liver transplants performed in Argentina; 74 (22.4%) were attributable to HCV. The annual number of liver transplants was available from a national organ registry for the years 1999 to 2013 (18). The proportion of liver transplants attributable to HCV was reported as 22.0% before the adoption of the Model for End Stage Liver Disease (MELD) based allocation and 22.4% after MELD allocation (21).
DISCUSSION
The goal of this analysis was to develop consensus estimates of the HCV epidemiology using best available published and unpublished data. The analysis was supported by an exhaustive literature search to identify relevant published studies in each country. The results were then reviewed with a panel of experts in each country, which provided hospital level and other unpublished data.
The data presented here can be used by researchers for a number of different purposes - modeling HCV disease burden, exploring the impact of immigration on HCV infections and determining potential response rate of therapies that vary by genotype. The next manuscript in this supplement will describe how these data can be used to project HCV disease progression using a mathematical model (13). However, the topic of immigration as a source of new HCV infections has been one of growing interest (121). The breakout of prevalence by age and gender (Figure 1) should provide sufficient detail to inform estimates of HCV infections for people moving across borders. It is interesting to note that HCV prevalence in most countries drops in individuals aged 30-35 (Figure 1), the average age of immigrants to most countries. Exceptions are found in countries where injection drug use (IDU) is the main source of new HCV infections
- Finland, Ireland, Luxembourg, Norway, Poland, Russia and Slovak Republic. Although HCV prevalence among 30-35 year olds is high in these countries, the IDU population with an HCV infection is an unlikely source of new immigrants. Thus, care should be taken in using the data presented here without adjustments.
A number of countries had centralized registries for diagnosed HCV cases - Finland, Ireland, Norway and Poland. Additionally, Luxembourg is in the planning stages for a centralized registry. Although Israel does not have a central registry for HCV, one national healthcare provider, CHS, covers over 60% of the population and retains detailed data. Russia has regional registries and work is underway to consolidate data across the country. Greece recently used an innovative technique of using a randomized national phone survey to quantify the diagnosis rate in the country (25). Although the method has some limitations, it does provide a quick technique to quantify diagnosis rates in countries where central registries are not available.
Great care was taken to combine data, analysis and expert panel consensus to provide the best available data. However, there were a number of limitations with this analysis. In some countries, very little data were available and the consensus numbers reported here may not be representative of the true state of HCV infection in the country. This highlights the need for more robust epidemiology studies to quantify HCV in the general population while considering the urban, rural and marginalized populations (IDU, people in institutions, etc.).
In countries where registries or epidemiology studies were available, it was assumed that the reported numbers are representative of the countries' HCV infected population. Data reported to the registries could have a selection bias, as testing and reporting may not be uniform across all subpopulations. In addition, viremic rate and genotype distribution were typically based on studies with relatively small sample sizes. Data from multiple studies were compared to minimize bias, but it is worth noting that both variables can change over time due to treatment rate and immigration.
The number of treated patients was estimated based on the drug sales when a central registry was not available. There was considerable variation in the number of treated patients across countries (Table 1). The use of drug sales data has a number of limitations including under-reporting, the use of drugs in multiple indications and the need to incorporate average adherence and genotype distribution. An effort was made to deal with these limitations by using expert panels. In countries where drug sales data were not available or where data are limited, the expert panel estimates were used, which may over- or under-estimate the total number of treated patients in the country.
This analysis highlights the need for more robust HCV epidemiology analyses that take into consideration the general population and sub-populations that may not be captured in a national study. The data required for a detailed analysis of HCV disease burden include anti-HCV and viremic prevalence, the number previously and newly diagnosed, the annual number of treated patients and the genotype distribution. Ideally, future studies will be conducted in multiple regions of the country to provide accurate national estimates as well as variations across different geographies.
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