World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma

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.

Figure 1

Flow diagram of studies selected for inclusion in the systematic review.

Figure 2

Seroprevalence of HBsAg, antiHCV‐Ab, both, and neither in patients with HCC in Europe and the Americas for countries with at least 100 HCC cases.

Figure 3

Seroprevalence of HBsAg, antiHCV‐Ab, both, and neither in patients with HCC in Eastern Asia and Western and Central Asia for countries with at least 100 HCC cases.

Figure 4

Seroprevalence of HBsAg, antiHCV‐Ab, both, and neither in patients with HCC in Northern Africa and Sub‐Saharan Africa for countries with at least 100 HCC cases.

Figure 5

Seroprevalence of HBsAg, antiHCV‐Ab, both, and neither in patients with HCC in countries for which at least 2 studies, and at least 150 cases, are available in each period before (light gray) and after the year 2000 (dark gray).

Figure 6

Proportion of HCC cases positive for any hepatitis virus seromarker (HBsAg, antiHCV‐Ab, or both) by country grouped by human development index (HDI).