Common Clinicopathological Features Of The Patients With Chronic Hepatitis B Virus Infection Who Developed Hepatocellular Carcinoma After Seroconversion To Anti-Hbs - A Consideration Of The Pathogenesis Of Hbv-Induced Hepatocellular Carcinoma And A Strategy To Inhibit It

Background/Aims: The incidence of hepatocellular carcinoma among patients who have seroconverted to anti-hepatitis B surface antigen (anti-HBs) remains controversial.Methodology: We report four patients with chronic hepatitis B virus (HBV) infection who had cleared HBsAg and had developed anti-HBs at a later time, but who developed hepatocellular carcinoma (HCC) eventually.Results: The common clinicopathological characteristics of the four patients were: An established diagnosis of precirrhosis or liver cirrhosis more than a decade previously, a long-standing normalization or stabilization at a low level of ALT values due to undetectable HBV DNA by the Amplicore Monitor assay, and a marked reduction of the fibrosis level in the non-tumorous liver obtained at HCC surgery or autopsy compared to the previous histology more than a decade previously. There was no fibrosis in the needle biopsy specimen from one patient.Conclusions: Our findings suggest that HCC due to HBV can occur in the serologically-cured stage if progression to pre-cirrhosis or cirrhosis already has occurred, where the fibrosis level has improved considerably because of the long-term absence of active HBV viremia and inflammation. Active medical intervention to prevent liver cirrhosis for chronic hepatitis B may have an important role in the inhibition of HCC in patients with chronic hepatitis B.