Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2022; 14(6): 1053-1073
Published online Jun 27, 2022. doi: 10.4254/wjh.v14.i6.1053
Impact of direct-acting antiviral regimens on hepatic and extrahepatic manifestations of hepatitis C virus infection
Iman Ibrahim Salama, Hala M Raslan, Ghada A Abdel-Latif, Somaia I Salama, Samia M Sami, Fatma A Shaaban, Aida M Abdelmohsen, Walaa A Fouad
Iman Ibrahim Salama, Ghada A Abdel-Latif, Somaia I Salama, Aida M Abdelmohsen, Walaa A Fouad, Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt
Hala M Raslan, Department of Internal Medicine, National Research Center, Giza 12622, Dokki, Egypt
Samia M Sami, Fatma A Shaaban, Department of Child Health, National Research Center, Giza 12622, Dokki, Egypt
Author contributions: Salama II and Raslan HA designed the review steps; Salama II, Salama SI, Abdel-Latif GA, Sami SM, and Shaaban FA were responsible for writing the minireview; Abdelmohsen AM and Fouad WA were responsible for manuscript reviewing; Salama II, Raslan HA, Salama SI, and Abdel-Latif GA did the final revision; Sami SM did the final editing; all the authors reviewed and approved the minireview.
Conflict-of-interest statement: All authors declare that they have 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: Iman Ibrahim Salama, MD, Professor, Department of Community Medicine Research, National Research Center, El Tahrir Street-Doki-Giza_Egypt, Giza 12622, Dokki, Egypt. salamaiman@yahoo.com
Received: January 17, 2022
Peer-review started: January 17, 2022
First decision: March 8, 2022
Revised: April 1, 2022
Accepted: May 22, 2022
Article in press: May 22, 2022
Published online: June 27, 2022
Processing time: 157 Days and 12.8 Hours
Abstract

Hepatitis C virus (HCV) is a common cause of liver disease and is associated with various extrahepatic manifestations (EHMs). This mini-review outlines the currently available treatments for HCV infection and their prognostic effect on hepatic manifestations and EHMs. Direct-acting antiviral (DAA) regimens are considered pan-genotypic as they achieve a sustained virological response (SVR) > 85% after 12 wk through all the major HCV genotypes, with high percentages of SVR even in advanced fibrosis and cirrhosis. The risk factors for DAA failure include old males, cirrhosis, and the presence of resistance-associated substitutions (RAS) in the region targeted by the received DAAs. The effectiveness of DAA regimens is reduced in HCV genotype 3 with baseline RAS like A30K, Y93H, and P53del. Moreover, the European Association for the Study of the Liver recommended the identification of baseline RAS for HCV genotype 1a. The higher rate of hepatocellular carcinoma (HCC) after DAA therapy may be related to the fact that DAA regimens are offered to patients with advanced liver fibrosis and cirrhosis, where interferon was contraindicated to those patients. The change in the growth of pre-existing subclinical, undetectable HCC upon DAA treatment might be also a cause. Furthermore, after DAA therapy, the T cell-dependent immune response is much weaker upon HCV clearance, and the down-regulation of TNF-α or the elevated neutrophil to lymphocyte ratio might increase the risk of HCC. DAAs can result in reactivation of hepatitis B virus (HBV) in HCV co-infected patients. DAAs are effective in treating HCV-associated mixed cryoglobulinemia, with clinical and immunological responses, and have rapid and high effectiveness in thrombocytopenia. DAAs improve insulin resistance in 90% of patients, increase glomerular filtration rate, and decrease proteinuria, hematuria and articular manifestations. HCV clearance by DAAs allows a significant improvement in atherosclerosis and metabolic and immunological conditions, with a reduction of major cardiovascular events. They also improve physical function, fatigue, cognitive impairment, and quality of life. Early therapeutic approach with DAAs is recommended as it cure many of the EHMs that are still in a reversible stage and can prevent others that can develop due to delayed treatment.

Keywords: Hepatitis C virus; Hepatic; Extrahepatic; Direct-acting antivirals; Impact

Core Tip: Direct-acting antivirals (DAAs) are achieving an over 85% sustained virological response in treating hepatitis C virus (HCV) infection. The risk factors for DAAs failure include old males, cirrhosis, and the presence of resistance-associated substitutions mainly in genotypes 1a and 3. The higher rate of hepatocellular carcinoma after DAA therapy may be due to offering DAA regimens to patients with advanced liver fibrosis and cirrhosis, where using interferon was contraindicated. The change in the growth of pre-existing subclinical, undetectable hepatocellular carcinoma upon DAA treatment might be a cause. DAAs are effective in treating HCV-associated mixed cryoglobulinemia, thrombocytopenia, rheumatological, renal, and cardiovascular diseases.