The global health burden of hepatitis C virus infection
Liver International
Special Issue: The global health burden of hepatitis C virus infection
Article first published online: 8 JUN 2011
DOI: 10.1111/j.1478-3231.2011.02537.x
© 2011 John Wiley & Sons A/S
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The hepatitis C virus (HCV) epidemic affects about 2.35% of the worldwide population, i.e. an estimated 160 million individuals (1). The limitations of current estimates, largely based on outdated sources or surveys on samples that are poorly representative of the general population, have been emphasized recently (1). Further difficulties arise when attempting to quantify the HCV-associated liver disease burden, for which estimates are partially available and only for selected, resource-rich countries. The picture is complicated if one considers that, because of ageing of the currently HCV-infected population, the burden of hepatitis C is expected to increase in the medium term. A study from USA (2) has shown that ageing of the HCV-infected population has already resulted in a significant increase in the prevalence of cirrhosis and hepatocellular carcinoma (HCC) cases reported in that country during the period 1996–2006. According to another work from the same country (3), the number of HCV-related cirrhosis cases is estimated to increase by 24% and that of decompensated cirrhosis cases by 50%. Unfortunately, similar accurate studies from other areas of the globe are lacking. It must be added that a synergistic effect on morbidity and mortality is anticipated because of the overlapping worldwide epidemics of HCV and the metabolic syndrome and therefore, the above estimates should be considered as conservative. Clearly, better data to estimate the baseline and trends of the HCV epidemic are urgently needed in order to plan effective prevention and management strategies.
Here, we present a series of manuscripts relating a systematic analysis of the HCV epidemiology literature, including an entire series of non-indexed sources that may constitute a framework for a better and more detailed appreciation of the global HCV epidemic. The last comprehensive global overview of HCV epidemiology was completed by WHO in 1999. Our goal was to develop an updated global analysis using sentinel countries in three regions, i.e. America, Europe and Asia/Australia (Fig. 1). In addition, we wanted to create a comprehensive reference for researchers working in this field. Thus, we were sure to include studies that we reviewed. Our decision to select countries was driven by two factors: the country had to provide adequate representations of the region and there had to be some HCV epidemiology studies available. Over 27 000 articles and documents from indexed journals and other non-indexed sources were screened. About 2600 items were selected based on relevance. When multiple data sources were available for any given key assumption, a systematic process using multi-objective decision analysis was used to select the most appropriate sources (4–7). When data were missing, analogues were used. The analysis focused on data relating to incidence and prevalence, major modalities of transmission, diagnosis rates and the relative proportion of HCV genotypes and subtypes. In addition, a patient flow model was developed to estimate treatment uptake and future trends.
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Figure 1. Hepatitis C virus prevalence among adults and genotype distribution.
When evaluating the HCV epidemiology, we realized that there were inherent limitations to our analysis, making comparison across countries difficult. The total number of HCV infections was not consistently analysed from country to country. In some countries, for example Australia, great care was taken to estimate the size of high-risk populations (e.g. injection drug users) and include them in the overall prevalence rate. In other countries, including USA and western European countries like France and Germany, the overall HCV prevalence was based on general population studies, which likely excluded many drug users and institutionalized individuals, thus leading to an underestimation of the true prevalence rate. For example, a study by Chak et al. (8) showed that the prevalence in USA is 27% higher if HCV infection among under-represented populations was added to NHANES estimates. In other countries, like Switzerland and India, the best estimate for the overall prevalence was derived from blood bank and/or pregnant women studies, which also underestimated the true infection rate. Although the inconsistencies made direct comparison of one country vs another difficult, it did highlight the fact that the true prevalence of HCV infection was likely to be higher than what is reported here and in other reports.
Across the board, there were no good data sources for the number of new infections. This is a major gap that makes efforts to eradicate the disease difficult. When data were reported, the distinction between acute and chronic cases was not always clear. In a report by Rantala and ECDCP, countries that had a robust registry (e.g. Sweden) appeared to have a much higher rate of new infections (9). In reality, the reported numbers were actually newly diagnosed cases, which included both acute and chronic infections. Thus, countries with a good surveillance system may sometimes appear to have a higher incidence.
In the first manuscript, Kershenobich et al. (10) describe a tool that was developed to predict the future prevalence of the disease in different countries and, more importantly, to understand the cause and effect relationship between key assumptions and future trends. It was applied to the US HCV-infected population, where the prevalence was estimated to decline 24% from 3.15 million in 2005 to 2.47 million in 2021, while the HCV-associated disease burden increased as the surviving infected population aged. 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 the treatment uptake was <2% of the infected population. Using US data as a model, these authors built a framework to analyse the baseline and trends of HCV-infected populations in other countries around the world.
Applying this framework to Argentina, Brazil, Mexico and Puerto Rico showed that the number of HCV-infected individuals in this region is steady or increasing (11). It is evident that Latin American countries have been very active in screening blood supplies, thus minimizing the risk of transmission through transfusion. However, as in most western countries, other risk factors are currently playing a major role in accounting for new infections. The number of diagnosed and treated patients is low or very low, thus increasing the burden of complications such as cirrhosis or HCC in the near and medium term.
The following manuscript relates the epidemiology of HCV in most European countries, plus Canada and Israel (12). Here, HCV prevalence was generally low, ranging between ≤0.5% (northern European countries) and ≥3% (Romania, rural areas in Greece, Italy and Russia). Differences in prevalence were explained by local variability in transmission routes or public health measures. The main risk for HCV transmission in countries with well-established HCV screening programmes and lower HCV prevalence was injection drug use. In other regions, however, it seems as if contaminated glass syringes and nosocomial infections continue to play an important role in transmission. Interestingly, in this relatively resource-rich region, immigration from endemic countries was sometimes a major factor impacting the total number of HCV-infected persons: approximately 70% of cases in Israel, 37% in Germany and 33% in Switzerland were not born in the country. These data underline the high heterogeneity of HCV epidemic across Europe, Canada and Israel.
Although the HCV pandemic has been systematically studied and characterized in North America and Europe, it has not received equivalent attention in other regions. The objective of the last manuscript was to characterize HCV epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population (13). Thus, a substantial proportion of the global HCV health burden lives in these regions; China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2%, several of the countries presented relatively high prevalence rates, such as Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infections and injection drug use are major risk factors in the region, and in some countries blood donors are still not universally screened. The implementation of surveillance systems to guide effective public health policy that may lead to the effective control of HCV spread is urgently warranted in these countries.
In conclusion, this Supplement of Liver International aims at providing an extensive coverage of the literature on the epidemiology of HCV. The major feature of this work is the collection and review of an unprecedented amount of data sources, most notably non-indexed, i.e. sources that are not available in scientific databases, such as websites and bulletins of government agencies and manuscripts that appeared in local non-English journals. We believe that this amount of information and the analysis thereof will be helpful to guide strategies to tackle the HCV epidemic globally and to identify gaps in the current knowledge of the HCV spread in selected areas. As such, this work should be considered as a starting point to buttress further research in the field.
This study was completed through the International Conquer C Coalition (I-C3) organization, an international, interdisciplinary group of physicians involved in the treatment and care of patients infected with HCV, aiming at increasing the understanding of the epidemiology, diagnosis, side effect management and treatment options for hepatitis C.
The IC-3 initiative has been led by Drs N. Afdhal and S. Zeuzem. Funding for this programme was provided through an educational grant provided by Merck & Co. Inc. and support from the Center for Disease Analysis. The Liver International supplement was funded by the Center for Disease Analysis, a division of Kromite. We are indebted to all I-C3 and Regional Conquer C Coalitions (R-C3) members for their contributions and comments.
Disclosures: FN Advisor: Schering-Plough, Roche, Novartis, Abbott and Gilead. AA Consultant: Roche, Gilead, Novartis, BMS, J&J, Merck, Schering-Plough. Grants: Gilead, Merck and BMS.
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