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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2020; 26(22): 2931-2947
Published online Jun 14, 2020. doi: 10.3748/wjg.v26.i22.2931
Liver-related effects of chronic hepatitis C antiviral treatment
Tea L Laursen, Thomas D Sandahl, Konstantin Kazankov, Jacob George, Henning Grønbæk
Tea L Laursen, Thomas D Sandahl, Konstantin Kazankov, Henning Grønbæk, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
Jacob George, Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Sydney NSW 2145, Australia
Jacob George, University of Sydney, Sydney NSW 2145, Australia
Author contributions: Laursen TL, Sandahl TD, Kazankov K, George J, and Grønbæk H designed the study; Laursen TL wrote the paper and Sandahl TD, Kazankov K, George J, and Grønbæk H critically revised it; all authors approved the final manuscript.
Conflict-of-interest statement: George J is supported by the Robert W Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant, No. APP1053206 and APP1149976) and Project grants, No. APP1107178 and APP1108422 and is on the advisory boards of Gilead, AbbVie, Novo Nordisk, MSD, Intercept, and Janssen; Grønbæk H received grants from the NOVO Nordisk Foundation, ‘‘Savværksejer Jeppe Juhl og hustru Ovita Juhls mindelegat”, AbbVie, and Intercept and is on the advisory board of Ipsen and Novartis; Laursen TL, Sandahl TD, and Kazankov K have no conflicts of interest 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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Tea L Laursen, MD, PhD, Doctor, Research Associate, Department of Hepatology and Gastroenterology, Aarhus University Hospital, 99 Palle Juul-Jensens Boulevard, Entrance C, Level 1, C116, Aarhus N DK-8200, Denmark. tealaurs@rm.dk
Received: January 31, 2020
Peer-review started: January 31, 2020
First decision: February 24, 2020
Revised: March 26, 2020
Accepted: May 30, 2020
Article in press: May 30, 2020
Published online: June 14, 2020
Processing time: 134 Days and 19.2 Hours
Abstract

More than five years ago, the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral (DAA) drugs. They proved highly efficient in curing patients with chronic hepatitis C (CHC), including patients with cirrhosis. The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis, but the exact cause of the expected benefit was unclear. Further, little was known about how the underlying liver disease would be affected during and after viral clearance. In this review, we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects, such as macrophage activation, and the time-dependent effects of therapy, with specific emphasis on inflammation, structural liver changes, and liver function, as these factors are all related to morbidity and mortality in CHC patients. It seems clear that antiviral therapy, especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis. There seems to be a time-dependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions. These improvements lead to favorable effects on liver function, followed by an improvement in cognitive dysfunction and portal hypertension. Overall, the data provide knowledge on the several beneficial effects of DAA therapy on liver-related parameters in CHC patients suggesting short- and long-term improvements in the underlying disease with the promise of an improved long-term prognosis.

Keywords: Chronic hepatitis C; Antiviral treatment; Inflammation; Liver fibrosis; Liver cirrhosis; Metabolic liver function; Galactose elimination capacity; Urea synthesis capacity; Portal hypertension; Hepatic encephalopathy

Core tip: Antiviral therapy of chronic hepatitis C, especially the achievement of a sustained virologic response, has several beneficial effects on liver-related parameters in chronic hepatitis C patients. There seems to be a time-dependent effect of therapy. Initially, liver inflammation ameliorates, followed by more discrete changes in structural liver lesions. These improvements are followed by beneficial effects on liver function, cognitive disturbances, and portal hypertension. Together, this suggests short- and long-term improvements in the underlying liver disease with the promise of an improved prognosis.