Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of hepatocellular carcinoma (HCC). In order to assess the relative contribution of HBV and HCV to HCC worldwide, and identify changes over time, we conducted a systematic review of case series published up to the year 2014. Eligible studies had to report seroprevalence of both hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV), alone and in combination, for at least 20 adult HCC cases. Studies using a first-generation enzyme-linked immunosorbent assay test for HCV were excluded. A total of 119,000 HCC cases in 260 studies were included from 50 countries. Most European and American countries show a preponderance of HCV over HBV and a substantial fraction of viral marker-negative cases. Asian and African countries generally show a predominance of HBV. The fraction of HCV-positive HCC cases is substantial in Taiwan, Mongolia, Japan, and Pakistan as well as in Western-Central Asia and Northern Africa. No eligible studies were available in Oceania, large parts of Africa, Eastern Europe, and Central Asia. The United States, Brazil, and Germany show evidence of higher prevalence of HCV in HCC since the year 2000. Conversely, Japan and Italy show a decline in the proportion of HCV-positive HCC. CONCLUSION: HBV and HCV are predominant causes of HCC in virtually all world areas, with a growing fraction of HCC cases in several countries attributable to HCV.