Virological significance of low-level hepatitis B virus infection in patients with hepatitis C virus associated liver disease.

The clinical and virological significance of low-level viremia by hepatitis B virus (HBV) in hepatitis C virus (HCV)-infected patients remains unclear. HBV-DNA and HCV-RNA were, therefore, quantitatively analyzed in livers and sera from co-infected patients. HBV-DNA and HCV-RNA were quantitated using real-time detection of polymerase chain reaction (RTD-PCR), based on Taq-Man chemistry, in 220 non-HCV-infected healthy volunteers and 93 HCV-infected patients without detectable HBsAg. Serum HBV-DNA was detected in 4 (1.8%) of 220 non-HCV-infected healthy volunteers and 32 (34.4%) of 93 HCV-infected patients without detectable HBsAg. HCV-infected patients displayed higher frequency of HBV infection than healthy volunteers (P < 0.0001). Hepatocellular carcinoma (HCC) was more frequent among co-infected patients than among HCV mono-infected patients (P < 0.001). However, quantities of HBV-DNA in sera from co-infected patients were very low (8-19,000 copies/ml). HBV-DNA was detected in liver tissue from co-infected patients at 2-20 copies per 100 hepatocytes, accounting for 1/1,000 to 1/10,000 of HBsAg positive patients. In livers of patients with HCC and HCV or HBV mono-infection, the viruses existed predominantly in non-cancerous tissue, with levels 10- to 1,000-fold and 1- to 100-fold higher than in cancerous tissue, respectively. In contrast, patients co-infected with HCV and HBV displayed decreased HBV levels in non-cancerous tissue, but no change in cancerous tissue. These results indicate that low-level HBV infection exists in HCV-infected patients. HCC was more common among HCV/HBV co-infected patients than among HCV mono-infected patients. HCV might initiate hepatocarcinogenesis, but does not necessarily determine progression to HCC.