Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease

Abstract

Summary The aim of the study was to determine whether past exposure to hepatitis B virus (HBV) influences the risk of the development of hepatocellular carcinoma (HCC) in Japanese patients with chronic liver disease (CLD). We conducted a hospital-based case-control study of 141 HCC patients with CLD and 151 controls with CLD but without HCC. Past exposure to HBV was assessed by antibody to hepatitis B core antigen (anti-HBc) positivity. Ninety-two patients (65%) with HCC were anti-HBc positive compared with 65 patients (43%) with CLD alone (P < 0.01). A multivariate analysis using logistic regression modelling revealed that anti-HBc positivity significantly increased the rsk of the development of HCC [odds ratio (OR) 2.0, P= 0.01]. In the anti-HBc-positive patients, a significantly increased risk of HCC was seen among the patients positive for anti-HBc alone (OR, 2.6; P < 0.01). However, a significant OR was not obtained among the patients with a transient HBV infection implied by positivity for both antibody to hepatitis B surface antigen and anti-HBc (OR, 1.5; P = 0.48). These results indicate that past exposure to HBV is a risk factor for HCC in Japanese CLD patients, especially when they have no serological evidence of immunity to HBV.Keywords: hepatocellular carcinoma; chronic liver disease; hepatitis B virus; hepatitis C virus; case-control study In Japan, the vast majority of patients with hepatocellular carcinoma (HCC) have chronic liver disease (CLD) such as chronic hepatitis and liver cirrhosis, and CLD patients frequently develop HCC during the follow-up period; patients with CLD are at increased risk of developing HCC (Ikeda et al, 1993;Tsukuma et al, 1993). Many CLD patients are, therefore, followed up periodically using ultrasonography (US) and serum a-fetoprotein (AFP) measurements to detect HCC at an early stage (Tanaka et al, 1990). Evaluation of the risk factors for HCC in CLD patients is imperative. Identification of the individuals who are at higher risk of HCC would contribute to the early diagnosis of this disease and to effective implementation of strategies for chemoprevention.Numerous epidemiological and biological studies have indicated that a chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) plays an important role in hepatocarcinogenesis (Bruix et al, 1989;Saito et al, 1990;Kim et al, 1991). As for HBV, serum hepatitis B surface antigen (HBsAg) positivity, which indicates a chronic HBV carrier state, is a well-established risk factor for HCC (Beasley et al, 1981;Chen et al, 1991). However, only a few reports have addressed the relationship between past exposure to HBV and HCC and, as yet, no definite conclusion has been established (Chiba et al, 1996;Yu et al, 1997).This hospital-based case-control study was conducted to evaluate whether past exposure to HBV, which was assessed by antibody to hepatitis B core antigen (anti-HBc) positivity, influenced the risk of developing HCC in Japanese CLD patients. Study populationThe HCC patient group comprised 141 co...

Safety and outcome of hepatitis B core antibody-positive donors in right-lobe living donor liver transplantation

“…In the absence of immunosuppression, the possibility of reactivation of HBV infection and progressive development of cirrhosis should be minimal. In a case-control study, 18 past exposure to HBV infection has been shown to increase the risk for the development of hepatocellular carcinoma by twofold in Japanese patients with chronic liver disease, but the odds ratio was not significant when anti-HBs was positive, as well. In patients with a biochemically and histologically normal liver, anti-HBc positivity alone has not been shown to be an independent risk factor for hepatocellular carcinoma.…”

Hepatitis B Virus DNA in Liver Tissue and Risk for Hepatocarcinogenesis in Patients with Hepatitis C Virus-Related Chronic Liver Disease

“…In many instances, occult HBV infection is associated with anti-HBc with or without anti-HBs, and serum antiHBc and anti-HBs are considered markers of past HBV infection that may also serve as useful markers for HCC risk factors [51][52][53] . However, no anti-HBs or anti-HBc can be detected in a significant proportion of patients with occult B infection [54] .…”

Antibody to hepatitis B core antigen is associated with the development of hepatocellular carcinoma in hepatitis C virus-infected persons: A 12-year prospective study

“…Several studies have shown that anti-HBc positivity was associated with the development of HCC in patients with HCV-associated chronic liver disease (11,(24)(25)(26). However, considering the natural history of all HCV infections, the results of those previous studies have some problems, i.e., the observation period was short and the research was performed in a retrospective manner in patients with chronic hepatitis and liver cirrhosis.…”

“…That is, anti-HBc, which was initially considered to be an index for the past HBV infection in which all HBV had been cleared, has emerged as a convincing marker of occult hepatitis B (19,(21)(22)(23). Also, several studies showed that the anti-HBc positivity was associated with the development of HCC in patients with HCV-associated chronic liver disease (11,(24)(25)(26), but these associations have not been clearly demonstrated.…”