Liver organoids as a primary human model to study HBV-mediated Hepatocellular carcinoma. A review

Abstract

Hepatitis B Virus (HBV) is the prevailing cause of chronic liver disease, which progresses to Hepatocellular carcinoma (HCC) in 75% of cases. It represents a serious health concern being the fourth leading cause of cancer-related mortality worldwide. Treatments available to date fail to provide a complete cure with high chances of recurrence and related side effects. The lack of reliable, reproducible, and scalable in vitro modeling systems that could recapitulate the viral life cycle and represent virus-host interactions has hindered the development of effective treatments so far. The present review provides insights into the current in-vivo and in-vitro models used for studying HBV and their major limitations. We highlight the use of three-dimensional liver organoids as a novel and suitable platform for modeling HBV infection and HBV-mediated HCC. HBV organoids can be expanded, genetically altered, patient-derived, tested for drug discovery, and biobanked. This review also provides the general guidelines for culturing HBV organoids and highlights their several prospects for HBV drug discovery and screening.

Keywords: Disease models; Hepatitis B Virus; Hepatocellular carcinoma; Liver organoids; Patient-derived organoids.