A meta-analysis of case–control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China

Abstract

We investigated whether concurrent infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) in China, a hyperepidemic area for these infections, was associated with a higher risk of causing hepatocellular carcinoma (HCC) than each infection alone in a metaanalysis in China, 32 case -control studies involving 3201 cases and 4005 controls, identified from a computer-based literature search from 1966 to 2004. The pooled odds ratio and 95% confidence interval (CI) for HBsAg positivity was 14.1 (95% CI: 10.6 -18.8); for anti-HCV/HCV RNA positivity was 4.6 (95% CI: 3.6 -5.9); for HBsAg positivity and anti-HCV/HCV RNA negativity were 15.6 (95% CI: 11.5 -21.3); for HBsAg negativity and anti-HCV/HCV RNA positivity were 8.1 (95% CI: 5.0 -13.0); and positivity for both HBsAg and anti-HCV/HCV RNA was 35.7 (95% CI: 26.2 -48.5). We conclude that HBV and HCV infections are important independent risk factors for HCC in China, and that dual infection by HBV and HCV is associated with a higher risk of causing HCC than each infection alone, suggesting a synergism between HBV and HCV. ). More than 500 000 new cases are currently diagnosed yearly, with an ageadjusted worldwide incidence of 5.5 -14.9 per 100 000 population (Llovet et al, 2003). About 110 000 persons die each year from HCC in China, which accounts for 45% of the deaths from HCC worldwide. China is also a hyperepidemic area for hepatitis B virus (HBV) infection (with an estimated carrier rate exceeding 10% in the general population) and hepatitis C virus (HCV) infection (with a prevalence of anti-HCV 3.1% of in the general population) (Xuezhong et al, 1999). HBV and HCV infections have each been shown to markedly increase the risk of developing HCC. In China, HBV has, for several decades, been the major cause of liver disease (Tang, 2001). Soon after the identification of HCV and the development of testing HCV infection, it has become increasingly evident that chronic HCV infection also plays an important role in chronic hepatic disease including HCC (Yano et al, 1993;Tsai et al, 1994). There have been several meta-analyses of the relation of HBV and HCV infections to HCC in China, but the relation of dual infection to HCC has not received similar attention. In fact, this is not rare in HCC patients and a higher morbidity in HCC patients with dual infection has been reported than in those with one infection (Benvegnu et al, 1994). The main difficulty in evaluating the relationship of dual infection to HCC is the rarity of concurrent infection in subjects without clinically evident liver disease. Only large case -control studies that include people unaffected by chronic liver diseases as controls can allow the interaction to be properly assessed. The aim of this meta-analysis is to assess the interaction between HBV and HCV infections among 32 casecontrol studies of HCC. MATERIALS AND METHODS Data sourcesWe searched the published Chinese literature from 1979 to February 2004 and Medline database from 1966 to February 2004 to identify case -control studies of the...

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“…Among studies performed outside South Europe, a recent meta-analysis of 32 Chinese case-control studies showed a moderate synergism between the two infections for HCC risk, with ORs of 15.6 for HBsAg positivity alone, 8.1 for anti-HCV positivity alone and 35.7 for positivity for both markers (Shi et al, 2005).…”

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