ThP5.8 - Familial hepatocellular carcinoma: a model for studying preventive and therapeutic measures

Abstract Aims Limited attention has been given to the role of primary genetic factors in hepatocellular carcinoma (HCC) especially as familial clusters of HCC are mostly described in areas of endemic hepatitis B virus (HBV) infection. The aim of the study was to review the literature on familial hepatocellular carcinoma (FHCC) and give evidence to suggest that FHCC may be a good model for studying preventive and therapeutic measures for HCC Methods Electronic searches of the Medline (PubMed) data base were performed to identify original published case studies on familial HCC. Results 16 case studies on FHCC were reported between 1965-2016. Even in the presence of HBV infection, FHCC seemed statistically unlikely to occur by chance. Genetic contributions may explain healthy and unhealthy HBsAg carriers, the male sex being predominantly affected, and HBV being directly oncogenic and causing HCC in the absence of cirrhosis in the younger patients. The highest risk of HCC occurs when a hereditary component is acting in concert with environmental factors such as HBV infection through epigenomic alterations. A family history of HCC increases the risk of FHCC independently of hepatitis due to a multifactorial inheritance including DICER 1 germline mutation and altered liver zonation. Epigenetic studies on monozygotic twins with HCC will identify the susceptible loci which can be used therapeuticallym. FHCC is a prognostic factor for improved survival in early resectable tumours with no/minimal cirrhosis. Conclusions HCC lacks a strong hereditary component but HCC-prone families of the familial type may provide a powerful model for studying preventive and therapeutic measures.