Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2021; 27(17): 1959-1972
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1959
Metabolic and cardiovascular complications after virological cure in hepatitis C: What awaits beyond
Mohamed Shengir, Mohamed Elgara, Giada Sebastiani
Mohamed Shengir, Department of Medicine, McGill University, Montreal, Quebec H3A0G4, Canada
Mohamed Elgara, Department of Internal Medicine, Hamad Medical Corporation, Doha 3050, Qatar
Giada Sebastiani, Department of Medicine, McGill University Health Center, Montreal, Quebec H4A3J1, Canada
Author contributions: Shengir M wrote the paper; Elgara M participated in writing the paper; Sebastiani G reviewed and critically revised the manuscript.
Supported by Junior 1 and 2 Salary Award from Fonds de la Recherche en Santé du Québec, No. 27127; Junior 1 and 2 Salary Award from Fonds de la Recherche en Santé du Québec, No. 267806; Research Salary from the Department of Medicine of McGill University; and Pfizer via Unrestricted Educational Grant.
Conflict-of-interest statement: Sebastiani G has acted as speaker for Merck, Gilead, Abbvie, Novonordisk, Novartis, Pfizer, served as an advisory board member for Merck, Intercept, Novartis, Gilead, Allergan, Pfizer and has received research funding from Merck and Theratec Inc. Shengir M has received honoraria from Gilead. Elgara M has nothing to declare.
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:
Corresponding author: Giada Sebastiani, MD, Associate Professor, Department of Medicine, McGill University Health Center, 1001 Blvd. Decarie, Montreal, Quebec H4A3J1, Canada.
Received: January 25, 2021
Peer-review started: January 25, 2021
First decision: February 27, 2021
Revised: March 6, 2021
Accepted: April 12, 2021
Article in press: April 12, 2021
Published online: May 7, 2021

The association between chronic hepatitis C (CHC) infection and extrahepatic manifestations (EHMs), particularly cardiometabolic diseases, has been extensively examined. However, there has still been insufficient evaluation for these EHMs after virological cure. Several multidirectional mechanisms have been proposed explaining the ability of hepatitis C virus (HCV) developing EHMs, cardiometabolic ones, as well as the effect of antiviral therapy to resolve these EHMs. Data on these manifestations after achieving sustained virologic response (SVR) are still conflicting. However, current evidence suggests that reversal of hepatic steatosis and its coexistent hypocholesterolemia after successful viral eradication led to unfavorable lipid profile, which increases cardiovascular disease (CVD) risk. Additionally, most observations showed that metabolic alterations, such as insulin resistance and diabetes mellitus (DM), undergo some degree of reduction after viral clearance. These changes seem HCV-genotype dependent. Interferon-based antiviral therapy and direct acting antiviral drugs were shown to minimize incidence of DM. Large epidemiological studies that investigated the effect of SVR on CVD showed great discrepancies in terms of results, with predominant findings indicating that CVD events decreased in patients with SVR compared to non-responders or untreated ones. In this review, we present a summary of the current knowledge regarding extrahepatic sequelae of CHC following SVR, which may have an impact on healthcare providers’ clinical practice.

Keywords: Chronic hepatitis C, Sustained virologic response, Hepatic steatosis, Diabetes mellitus, Cardiovascular disease

Core Tip: The implementation of direct acting antiviral drugs has dramatically changed the landscape of hepatitis C virus (HCV) treatment, with over 95% of patients achieving sustained virologic response (SVR). Although consistent evidence demonstrated better outcomes for both hepatic and extrahepatic complications after viral clearance, data on cardiometabolic manifestation showed inconsistent results. In this review, we are shading light on the latest findings about cardiometabolic extrahepatic manifestations post-SVR. These updates may guide clinicians engaged in HCV care to integrate in their management post-viral eradication risks and subsequent long-term care.