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World J Gastroenterol. Jun 7, 2022; 28(21): 2251-2281
Published online Jun 7, 2022. doi: 10.3748/wjg.v28.i21.2251
Viral hepatitis and hepatocellular carcinoma: From molecular pathways to the role of clinical surveillance and antiviral treatment
Leonardo Stella, Francesco Santopaolo, Antonio Gasbarrini, Maurizio Pompili, Francesca Romana Ponziani
Leonardo Stella, Francesco Santopaolo, Antonio Gasbarrini, Maurizio Pompili, Francesca Romana Ponziani, Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
Author contributions: Stella L, Santopaolo F, Gasbarrini A, Pompili M, Ponziani FR were responsible for the manuscript concept and design, revision of data, interpretation of data, critical revision of the manuscript for important intellectual content; Stella L, Santopaolo F, Ponziani FR drafted the manuscript; and all authors were involved in the final approval of the final version of the manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Francesca Romana Ponziani, MD, PhD, Research Assistant, Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, Rome 00168, Italy. francesca.ponziani@gmail.com
Received: September 13, 2021
Peer-review started: September 13, 2021
First decision: November 16, 2021
Revised: December 8, 2021
Accepted: April 26, 2022
Article in press: April 26, 2022
Published online: June 7, 2022
Processing time: 261 Days and 13.8 Hours
Abstract

Hepatocellular carcinoma (HCC) is a global health challenge. Due to the high prevalence in low-income countries, hepatitis B virus (HBV) and hepatitis C virus infections remain the main risk factors for HCC occurrence, despite the increasing frequencies of non-viral etiologies. In addition, hepatitis D virus coinfection increases the oncogenic risk in patients with HBV infection. The molecular processes underlying HCC development are complex and various, either independent from liver disease etiology or etiology-related. The reciprocal interlinkage among non-viral and viral risk factors, the damaged cellular microenvironment, the dysregulation of the immune system and the alteration of gut-liver-axis are known to participate in liver cancer induction and progression. Oncogenic mechanisms and pathways change throughout the natural history of viral hepatitis with the worsening of liver fibrosis. The high risk of cancer incidence in chronic viral hepatitis infected patients compared to other liver disease etiologies makes it necessary to implement a proper surveillance, both through clinical-biochemical scores and periodic ultrasound assessment. This review aims to outline viral and microenvironmental factors contributing to HCC occurrence in patients with chronic viral hepatitis and to point out the importance of surveillance programs recommended by international guidelines to promote early diagnosis of HCC.

Keywords: Hepatitis C virus; Hepatitis B virus; Hepatitis D virus; Hepatocellular carcinoma; Cirrhosis; Liver

Core Tip: Chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) infection represents a global health burden leading to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Among these complications, HCC accounts for 3.5% of all deaths worldwide. Thus, the understanding of the role of chronic hepatitis virus infection in HCC development is necessary in order to clarify the mechanisms underlying oncogenesis and design future treatments for this cancer. This review outlines pathophysiological and molecular pathways that contribute to carcinogenesis in HBV, HCV and HDV chronic infection focusing on the impact of clinical surveillance and antiviral treatment on the risk of HCC development.