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Background and aims The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk. Methods This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers. Results The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean±SD, 4.35±1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30–75-years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither. Conclusions Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.

The sodium taurocholate co-transporting polypeptide (NTCP), encoded by SLC10A1, was recently identified as a receptor for HBV. We assessed the association of the p.Ser267Phe variant (rs2296651) with chronic hepatitis B (CHB) serostatus, cirrhosis and hepatocellular carcinoma (HCC) in patients with CHB.The variant was genotyped in 3801 patients with CHB and 3801 matched hepatitis B surface antigen (HBsAg) seronegative individuals. ORs with 95% CIs for the variant's association with CHB, cirrhosis and HCC were estimated using logistic regression.In patients with CHB, the S267F variant was observed in 515 (18.5%) controls, 40 (17.2%) cirrhosis only cases, 49 (13.2%) non-cirrhotic HCC cases, and 52 (12.7%) cirrhotic-HCC cases. After adjustment for known risk factors, S267F was significantly associated with decreased risk for cirrhosis (OR 0.65 (95% CI 0.49 to 0.86), p=0.002) and HCC (OR 0.55 (95% CI 0.42 to 0.72), p0.001). This association persisted for non-cirrhotic and cirrhotic-HCC. Compared with patients with HBV DNA levels greater than 10(5) copies/mL who carried the GG genotype, patients who had undetectable HBV DNA and the GA or AA genotypes had a 25-fold decreased risk of developing HCC (OR 0.04 (95% CI 0.02 to 0.11), p0.001). The AA genotype was also associated with HBsAg seronegativity (OR 0.13 (95% CI 0.05 to 0.34), p0.001).The SLC10A1 (NTCP) S267F variant is independently associated with decreased risk of cirrhosis and HCC, and resistance to CHB infection. Together with serum HBV DNA levels, S267F may help to identify patients with CHB with very low risk of HCC.

Aim The aim of this study was to explore the community-level risk factors, such as high hepatitis C viruse (HCV)-RNA positive rate and limited medical resources in a township, for HCV infection, one major cause of liver cirrhosis and hepatocellular carcinoma. Methods This study enrolled 23 820 residents living in 155 villages of seven townships in Taiwan in 1991–2 to explore both individual and community risk factors for HCV infection. Antibodies against HCV (anti-HCV), HCV-RNA and HCV genotype in serum samples were determined by enzyme immunoassay, PCR and melting curve analysis, respectively. Results The overall anti-HCV seroprevalence was 5.5%, HCV-RNA was detectable in 68.1% of the seropositives of anti-HCV, and genotype 1 was the most prevalent genotype (54.6%). Personal risk factors for the seropositivity of anti-HCV included older age, female gender, low educational level and history of blood transfusion. Based on the multilevel analysis, persons living in villages with high HCV-RNA-positive rates and limited healthcare resources had an increased seroprevalence of anti-HCV after adjustment for individual risk factors. The multivariate-adjusted prevalence OR (95% CI) was 3.49 (1.80 to 6.76) and 8.48 (5.07 to 14.20) for villages with medium and high HCV-RNA positive rate, respectively. The multivariate-adjusted OR (95% CI) was was 1.75 (0.76 to 4.01) and 3.91 (2.25 to 6.80), respectively, for villages with medium and poor healthcare resources. Conclusions This study suggests that community risk factors contribute significantly to the variation in anti-HCV seroprevalence. It implies both the adequacy of healthcare resources and the treatment of patients positive for HCV-RNA may prevent individual residents from the acquisition of HCV infection from the community.