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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2021; 27(40): 6737-6749
Published online Oct 28, 2021. doi: 10.3748/wjg.v27.i40.6737
Hepatocellular carcinoma risk after viral response in hepatitis C virus-advanced fibrosis: Who to screen and for how long?
Adriana Ahumada, Laura Rayón, Clara Usón, Rafael Bañares, Sonia Alonso Lopez
Adriana Ahumada, Laura Rayón, Clara Usón, Rafael Bañares, Sonia Alonso Lopez, Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
Adriana Ahumada, Rafael Bañares, Sonia Alonso Lopez, Liver Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid 28007, Spain
Rafael Bañares, Medicine, Universidad Complutense de Madrid, Madrid 28006, Spain
Rafael Bañares, Sonia Alonso Lopez, Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid 28029, Spain
Author contributions: Ahumada A, Bañares R and Alonso López S have been involved in conception and drafting the article; Bañares R and Alonso López S have made critical revisions related to important intellectual content of the manuscript; Rayón L and Usón C have been involved in acquisition of data and drafting the article; Ahumada A, Rayón L, Usón C, Bañares R and Alonso López S have read and approved the final manuscript.
Conflict-of-interest statement: Adriana Ahumada has received fees for serving as a speaker and a grant from Abbvie and personal fees for serving as a speaker and for Gilead. Laura Rayón, Clara Usón and Rafael Bañares have nothing to disclose. Sonia Alonso has received fees for serving as a speaker and consultant from Abbvie and Gilead.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sonia Alonso Lopez, MD, PhD, Attending Doctor, Consultant Physician-Scientist, Doctor, Senior Researcher, Liver Unit, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain. salonsol@telefonica.net
Received: April 11, 2021
Peer-review started: April 11, 2021
First decision: June 13, 2021
Revised: June 24, 2021
Accepted: September 19, 2021
Article in press: September 19, 2021
Published online: October 28, 2021
Processing time: 198 Days and 21.2 Hours
Abstract

Hepatitis C virus (HCV) chronic infection is associated with fibrosis progression, end-stage liver complications and HCC. Not surprisingly, HCV infection is a leading cause of liver-related morbidity and mortality worldwide. After sustained virological response (SVR), the risk of developing hepatocellular carcinoma is not completely eliminated in patients with established cirrhosis or with advanced fibrosis. Therefore, lifelong surveillance is currently recommended. This strategy is likely not universally cost-effective and harmless, considering that not all patients with advanced fibrosis have the same risk of developing HCC. Factors related to the severity of liver disease and its potential to improve after SVR, the molecular and epigenetic changes that occur during infection and other associated comorbidities might account for different risk levels and are likely essential for identifying patients who would benefit from screening programs after SVR. Efforts to develop predictive models and risk calculators, biomarkers and genetic panels and even deep learning models to estimate the individual risk of HCC have been made in the direct-acting antiviral agents era, when thousands of patients with advanced fibrosis and cirrhosis have reached SVR. These tools could help to identify patients with very low HCC risk in whom surveillance might not be justified. In this review, factors affecting the probability of HCC development after SVR, the benefits and risks of surveillance, suggested strategies to estimate individualized HCC risk and the current evidence to recommend lifelong surveillance are discussed.

Keywords: Hepatitis C virus; Hepatocellular carcinoma; Liver fibrosis; Surveillance; Sustained virologic response; Epigenetic changes; Predictive models; Cost-effectiveness

Core Tip: Hepatocellular carcinoma (HCC) risk is reduced after sustained viral response, but a substantial threat persists over time. Understanding the natural history of hepatitis C virus infection and the variable influence of viral eradication in the molecular and epigenetic changes that occur during infection are essential to explain the different risk of developing HCC in patients with advanced fibrosis. The definition of the appropriate tools to estimate the individual risk of HCC after antiviral treatment providing reliable recommendations about HCC surveillance is probably the most important challenge to be clarified in this field.