Association of Chronic Hepatitis B With Colorectal Cancer and Its Dual Impact on Colorectal Liver Metastasis: A Narrative Review

Abstract

Viral hepatitis B is infamous for being contracted in young adulthood and adolescence, as high-risk behaviors like unprotected sexual intercourse and intravenous drug abuse are common. Most infections caused by the hepatitis B virus (HBV) are cleared without any long-term sequelae, but some may persist and cause chronic hepatitis B (CHB). This chronicity may produce a state of prolonged inflammation and significantly increase the risk of developing colorectal adenomas (CRA) and colorectal carcinomas (CRC). The aim of this review is to deep-dive into the mechanisms by which CHB may predispose a patient to develop CRA and, more grimly, CRC. It also focuses on studying the influence of CHB on colorectal cancer liver metastases (CRLM). We conducted a comprehensive literature search using databases like PubMed and Google Scholar, focusing on studies that investigate the role of HBV in colorectal carcinogenesis and CRLM rates in patients suffering from CHB. Chronic inflammation, viral protein interactions with tumor suppressor genes, alteration of cellular pathways such as wingless-related integration site (Wnt) signaling, and extrahepatic accumulation of hepatitis B surface antigen (HBsAg) were the key mechanisms identified. Quite peculiarly, CHB, which is thought to increase the risk for CRA, seemed to protect against CRLM probably due to its sclerosing effect on the liver parenchyma and due to certain immune-mediated mechanisms that suppress tumor growth. Nonetheless, high viral count or the presence of hepatitis B envelope antigen (HBeAg) was found to increase the risk for CRLM, potentially due to increased angiogenesis in the liver. These findings provide convincing evidence that enhanced colonoscopic screening and stronger management protocols for patients suffering from it have the potential to reduce the risk of developing CRC and CRLM.

Keywords: adenoma carcinoma sequence; chronic hepatitis b; colorectal adenoma; colorectal cancer; colorectal liver metastasis; hepatitis b virus; screening colonoscopy; tumor suppressor gene (tp53) mutation.

Figure 1. Mechanisms of hepatitis B virus (HBV) induced colorectal carcinogenesis.

DNA: deoxyribonucleic acid, HBx: hepatitis B protein X, Wnt: wingless-related integration site, TP53: tumor protein 53, APC: adenomatous polyposis coli. Created using BioRender.com.

Figure 2. Dual role of hepatitis B infection in colorectal liver metastasis.

TNF-β: tumor necrosis factor-β, IL-1: interleukin-1, PDGF: platelet-derived growth factor, miRNA: microribonucleic acid, FIB-4: fibrosis-4 index for liver fibrosis; APRI- aspartate aminotransferase-to-platelet ratio index, HBeAg: hepatitis B envelope. Created using BioRender.com.