Hepatocellular Carcinoma in Hepatitis B Virus-Infected Patients and the Role of Hepatitis B Surface Antigen (HBsAg).

Satinder P. Kaur,Hao Wei Chen,Andreea M. Catana,Hamidreza Karimi-Sari,Andrew Grees,Daryl T. Y. Lau,Arslan Talat

doi:10.3390/jcm11041126

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Hepatitis B virus (HBV) infection is among the main risk factors for HCC. The risk of HCC is not eliminated completely after viral suppression, due to HBV DNA integrated into human chromosomes. Cirrhosis, HBV viral DNA levels, age, male gender, the immune response of the host against HBV, and a combination of obesity and diabetes are among the main risk factors for HCC. Active viral replication and long-standing active disease with inflammation are associated with a higher risk of HCC. Treatment of HBV with nucleos(t)ide analogues (NAs) decreased HCC risk by effectively decreasing viral load and inflammation. Similar risk factors have been reported in hepatitis B patients after seroclearance. Studies have reported decreased risk of HCC after seroclearance, but there were also conflicting results from a few studies indicating no difference in risk of developing HCC. The difference in HCC rates could be because of other factors such as coinfection, occult HBV infection, family history, HBV genotype, and other comorbidities. Due to the persistent risk of HCC after seroclearance, HCC surveillance is critical for early detection, especially in high-risk patients. However, long-term studies might be needed to further validate the results.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related mortality
The complete cure is difficult to achieve in chronic hepatitis B (CHB), since Hepatitis B virus (HBV) DNA is integrated into the host genome, and viral closed circular DNA (cccDNA) is detected in the liver even after a sterilizing cure, which can cause a reactivation
This study showed that PAGE-B scores with cut-off values of low- (≤9), intermediate(10–17), and high-risk (≥18) could predict the risk of hepatocellular carcinoma (HCC) development after HBV surface antigen (HBsAg) clearance

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related mortality. HCC surveillance is an effective measure for early cancer detection, especially in high-risk patients. The complete cure is difficult to achieve in chronic hepatitis B (CHB), since HBV DNA is integrated into the host genome, and viral cccDNA is detected in the liver even after a sterilizing cure, which can cause a reactivation. The term “functional cure” was coined during the combined American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) workshop in 2016 It was defined as sustained, undetectable HBV surface antigen (HBsAg) and HBV DNA in serum with or without seroconversion to HBsAb, and selected as the goal for newer HBV therapies [8]. This review will focus on HCC risk in patients with CHB after viral suppression

Risk Factors for HCC Development in Chronic HBV Infection

Findings

Conclusions