Risk Prediction Model for HCC in Subjects Without Apparent Chronic Liver Disease: A Dilemma in Asia

We read with interest the paper “A risk prediction model for hepatocellular carcinoma in the general population without traditional risk factors for liver disease” published in a recent issue of Journal of Gastroenterology and Hepatology [1]. It is an interesting study that investigated a large cohort of subjects lacking traditional risk factors for hepatocellular carcinoma (HCC) in South Korea. A new prediction model was proposed to stratify HCC risk in the general population without risk factors for chronic liver disease. However, a few issues remain to be clarified, especially when this study was performed in Asia. In this study, 171 (0.12%) out of 138 452 individuals developed HCC after a median follow-up of 9 years. The annual incidence was considered extremely low, only 0.013%. A major concern here is that many countries in Asia are endemic for chronic hepatitis B virus (HBV) infection. Although subjects with hepatitis B were removed from the analysis, presumably by the absence of hepatitis B surface antigen (HBsAg), we still cannot reliably exclude subjects with occult hepatitis B infection (OBI) in this study population. OBI was often defined as the presence of HBV DNA in serum and/or liver tissue without detectable HBsAg. Abundant studies show that HBsAg-negative chronic hepatitis patients are often positive for HBV DNA. A recent meta-analysis disclosed that the overall pooled OBI prevalence in children and adolescents was 7.5% [2]. Based on different serological criteria, the overall prevalence of OBI was as follows: 7.9% for HBsAg-negative, 3.2% for HBsAg-negative and anti-hepatitis B core antigen (HBc)-negative, and 8.9% for HBsAg-negative and anti-HBc-positive. The above data suggest that OBI is not uncommon in individuals seronegative for HBsAg, and a substantially high proportion of patients with OBI could be included in the analysis by Song et al. [1]. Notably, anti-HBc is a marker when people are exposed to HBV, and it can be detected before the appearance of HBsAg. In this regard, anti-HBc is probably a more reliable surrogate to exclude HBV infection, especially in HBV-endemic areas. In summary, OBI should be considered in subjects without apparent risk factors for HCC who ultimately develop HCC. When a risk model for HCC is proposed in this setting, anti-HBc should be incorporated in the analysis to define the outcome. This study was supported by a grant from Taipei Veterans General Hospital (V114C-004), Taiwan. The authors declare no conflicts of interest.