Impact of occult hepatitis B virus infection and high-fat diet on hepatocellular carcinoma development

In the areas where viral infections are more common, the incidence of hepatocellular carcinoma (HCC) has declined. This is largely attributed to the availability of vaccines against hepatitis B virus (HBV), antiviral treatments, and a change in diet with healthier foods. However, in the Western world, the HCC incidence rate has risen steadily, probably due to an increased prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD), a condition that has increasingly been considered an important risk factor for HCC. Despite this, in 2019, 41% of HCC cases were diagnosed globally and a majority of diagnosed cases from mainland China were related to HBV. Some HCC cases tested negative for hepatitis B surface antigen (HBsAg) but tested positive for HBV-DNA in blood. This is considered an occult HBV infection (OBI). OBI is related to various mutations in the viral genome, which modifies host immunity, subsequently leading to the long-term persistence of cccDNA in the nucleus of infected hepatocytes. Many OBIs are associated with HBV variants carrying mutations in preS/S genomic regions, which occur either spontaneously or as a result of antiviral treatments. OBIs are also frequently reported in HBV-vaccinated individuals. HBV variants post-HBV vaccination carry mutations in the preS area. This review discusses the relationship between preS variant-related OBIs and the development of HCC in the context of a high-fat diet, one of the preventable behavioral risk factors for MAFLD.