The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide☆
Introduction
End-stage liver disease represents a major source of morbidity and mortality worldwide. The World Health Organization (WHO) estimates that in 2002 cirrhosis and primary liver cancer caused 783,000 and 619,000 deaths, respectively, [1]. Taken together, these conditions represented approximately one of every forty deaths (2.5%) worldwide.
Among primary liver cancers occurring worldwide, hepatocellular carcinoma (HCC) represents the major histologic type and likely accounts for 70% to 85% of cases [2]. Cirrhosis precedes most cases of HCC, and may exert a promotional effect via hepatocyte regeneration [3], [4]. Compared with other causes of cirrhosis, chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is associated with a higher risk of developing HCC [3], [5]. Alcohol abuse represents a leading cause of cirrhosis and is also a major contributor to HCC in many parts of the world, with some evidence for a synergistic effect in the presence of HBV or HCV infection [6], [7]. Other factors appear to be of regional or local importance [8], [9]. For example, dietary aflatoxin exposure in parts of Africa and Asia has been associated with primary liver cancer, especially in hosts with chronic HBV infection [8].
An understanding of the relative contribution of various etiologies to disease burden is important for setting public health priorities and guiding prevention programs [10], [11]. The World Health Organization’s Global Burden of Disease (GBD) 2000 project aims to quantify the burden of premature morbidity and mortality from over 130 major causes [1], [12]. Liver cancer and cirrhosis are included in the analysis, but with the exception of alcohol, the etiologies underlying these diseases have not been well accounted for [1], [11], [13]. In particular, HBV and HCV infections have been poorly characterized in previous WHO estimates since these were based primarily on the acute effects of infection and omitted the associated burdens of chronic liver disease [10], [11].
The attributable fraction represents the proportion of disease occurrence that potentially would be prevented by eliminating a given risk factor. For cirrhosis, a systematic analysis of attributable fractions has been lacking altogether. For HCC, previous estimates of the attributable fractions due to HBV and HCV are available but are not comprehensive and do not correspond to the regional designations and related conventions of the current GBD project [14]. In this study, we sought to estimate the attributable fractions of cirrhosis and HCC due to HBV infections and HCV infections globally and divided according to WHO GBD-based regions.
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Regions
Regions used in this analysis were based on subdivisions of the six primary WHO regions (AFR, African; AMR, The Americas; EMR, Eastern Mediterranean; EUR, European; SEAR, South-East Asian; and WPR, Western Pacific), as defined in the GBD 2000 project [1]. Each region is designated by the three- or four-letter region code followed by a one-letter suffix, corresponding to the mortality pattern of its member countries: A = very low child, low adult mortality; B = low child, low adult mortality; C = low
Results
For cirrhosis, we included a total of 43 study populations (median number per region, 4; range, 2–7) in the analysis (Table 2). For HCC, the total number of study populations that contributed data to the analysis was 52 (median, 4; range, 3–10) (Table 3). Most studies were set in hospitals and were conducted during the mid- or late-1990s, after the introduction of second-generation anti-HCV assays. Typically, the studies specified diagnosis via histology or imaging techniques, supplemented by
Discussion
This study provides a detailed regional accounting of the underlying contributions of HBV and HCV infections to end stage liver disease worldwide and is the first such effort to include cirrhosis. We showed that chronic viral hepatitis infections likely account for the majority of both cirrhosis and HCC globally and in nearly all regions of the world.
One of the strengths of our analysis was that it employed simple and transparent methods. Our estimates of attributable fractions were derived
Acknowledgments
We thank Dr. Jan Drobeniuc for his assistance in evaluating Russian-language and other articles and Drs. Susan Goldstein and Claudia Stein for helpful advice and comments regarding our analytic approach. U.S. Office of Management and Budget policy disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention.
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The authors who have taken part in this study declared that they have no relationship with the manufacturers of the drugs involved either in the past or present and did not receive funding from the manufacturers to carry out their research.