Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2021; 27(13): 1267-1282
Published online Apr 7, 2021. doi: 10.3748/wjg.v27.i13.1267
Metabolic complications of hepatitis C virus infection
Rahul Chaudhari, Sherouk Fouda, Ashik Sainu, Joseph M Pappachan
Rahul Chaudhari, Department of Medicine, Pennsylvania Hospital of the University of Pennsylvania, Pennsylvania, PA 19104, United States
Sherouk Fouda, School of Health and Biomedical Sciences, RMIT University, Melbourne VIC 3000, Australia
Ashik Sainu, Department of Gastroenterology and Hepatology, Aster Oman Hospital, Al Ghubra, Muscat OM 133, Oman
Joseph M Pappachan, Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
Joseph M Pappachan, Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
Joseph M Pappachan, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
Author contributions: Chaudhari R and Fouda S performed extensive literature review and drafted the manuscript and share the first authorship jointly; Sainu A added points especially the hepatologic side of the work with additional literature review and revision; Pappachan JM conceived the idea, inputted additional scientific points especially the metabolic aspects, revised the entire work critically, and approved the final version for publication.
Conflict-of-interest statement: Dr. Pappachan and co-authors of this paper have nothing to disclose.
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: Joseph M Pappachan, FRCP, MD, Consultant Physician-Scientist, Honorary Research Fellow, Senior Researcher, Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Preston PR2 9HT, United Kingdom.
Received: January 23, 2021
Peer-review started: January 23, 2021
First decision: February 10, 2021
Revised: February 10, 2021
Accepted: March 12, 2021
Article in press: March 12, 2021
Published online: April 7, 2021

Hepatitis C virus (HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.

Keywords: Chronic hepatitis C infection, Insulin resistance, Metabolic syndrome, Cardiovascular diseases, Fatty liver, Diabetes mellitus

Core Tip: Available evidence proves a strong association between hepatitis C virus (HCV) and metabolic complications such as hyperlipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes mellitus. De novo development of insulin resistance and hepatic steatosis in chronic HCV infection influences the disease progression in the liver and enhances overall morbidity and mortality. The influence of metabolic diseases on HCV infection can increase disease severity. The interplay between HCV major proteins and the liver-muscle-adipose axis is complex and still not fully elucidated. Coexistence of metabolic diseases such as diabetes mellitus and HCV infection are also known to result in adverse outcomes of both disorders. There is evidence that successful treatment halts the progression of liver disease, but more studies are required on how treatment influences the metabolic manifestations.