Hepatitis B virus transmission and hepatocarcinogenesis: a 9 year retrospective cohort of 13 676 relatives with hepatocellular carcinoma

Viral hepatitis、alcohol、smoking、familial tendency and aflatoxin are well-known risk factors for hepatocellular carcinoma (HCC) [1–3]. Several cohort studies have found that HBsAg carriers are at highest risk (relative risk ranges from 7 to 98) of developing HCC、while other factors appear to have a lower risk (relative risk ranges from one to four) [1–3]. Nevertheless、a low risk of HCC in asymptomatic HBsAg carriers was observed in another study [4]. The reason for this discrepancy attracted our attention. One clue is that approximately 70% of the HBsAg positive patients with HCC acquired their HBV infection perinatally [5–7]. Because familial aggregation is a characteristic of HCC、a nationwide survey of relatives of patients with HCC was done between 1992 and 1997. The original purposes of the survey were to study viral infection status and have an early detection of HCC in HCC families [8–11]. The survey included the parents of the index patients、the index patients themselves、and their children. Given the same transmission route (perinatal transmission) as the index patients、the index patient generation had a high prevalence of HBsAg (approximately 60%) [8–10]. In contrast、the prevalence of HBsAg was approximately 30% in the child generation [8–10]. This difference may result from a difference in transmission route. The index patients were predominantly male、and the prevalence of HBsAg in their spouse is assumed to approximate that in the general population (15– 20%) [12,13]. Therefore、the risk of perinatal transmission should be lower in the child generation than in the index patient generation. However、the prevalence of HBsAg in the child generation (30%) was still significantly higher than that in the general population. This phenomenon may be caused by high horizontal transmission owing to high paternal (mostly HCC) HBsAg prevalence (.60%) [14]. Therefore、this study uses the index patient and child generations to assess the role of perinatal transmission of hepatitis B virus (HBV) in hepatocarcinogenesis. This retrospective cohort study examined the difference in HCCrelated death rates between these two generations of HCC with different HBV transmission routes、and determined the underlying factors for HBsAg carriers to progress to severe liver disease、such as HCC