Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2021; 27(21): 2771-2783
Published online Jun 7, 2021. doi: 10.3748/wjg.v27.i21.2771
Direct antiviral agents in hepatitis C virus related liver disease: Don’t count the chickens before they’re hatched
Stella Compagnoni, Erica Maria Bruno, Giorgio Madonia, Marco Cannizzaro, Salvatore Madonia
Stella Compagnoni, Erica Maria Bruno, Department of Internal Medicine, V. Cervello Hospital, University of Palermo, Palermo 90146, Italy
Giorgio Madonia, Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo 90127, Italy
Marco Cannizzaro, Department of Emergency Medicine, A. Ajello Hospital, Trapani 91026, Italy
Salvatore Madonia, Department of Internal Medicine, V. Cervello Hospital, Palermo 90146, Italy
Author contributions: Compagnoni S and Bruno EM contributed to the section on relevant concomitant disease; Madonia G contributed to the section on hepatocellular carcinoma; Cannizzaro M contributed to the section on concomitant hepatitis B virus infection; Madonia S contributed to the section on advanced liver disease and coordinated the writing of the paper; All the authors have read and approved the final manuscript.
Conflict-of-interest statement: There is no conflict of interest associated with any of the authors who contributed to this manuscript.
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: Salvatore Madonia, MD, Doctor, Department of Internal Medicine, V. Cervello Hospital, Via Trabucco n 180, Palermo 90146, Italy.
Received: January 22, 2021
Peer-review started: January 25, 2021
First decision: February 28, 2021
Revised: March 26, 2021
Accepted: April 28, 2021
Article in press: April 28, 2021
Published online: June 7, 2021

Since molecules with direct-acting antiviral (DAA) became available, the landscape of the treatment of hepatitis C virus (HCV) infection has completely changed. The new drugs are extremely effective in eradicating infection, and treatment is very well tolerated with a duration of 8-12 wk. This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages, identifying some clinically relevant hot topics. First, do the rates of virological response remain as high when patients with more advanced cirrhosis are considered? Large studies have shown slightly lower but still satisfactory rates of response in these patients. Nevertheless, modified schedules with an extended treatment duration and use of ribavirin may be necessary. Second, does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer? Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis. In contrast, the risk of recurrence seems to be unaffected by viral clearance; however, DAA treatment improves survival because of the reduced risk of progression of liver disease. Third, can HCV treatment also have favorable effects on major comorbidities? HCV eradication is associated with a reduced incidence of diabetes, an improvement in glycemic control and a decreased risk of cardiovascular events; nevertheless, a risk of hypoglycemia during DAA treatment has been reported. Finally, is it safe to treat patients with HCV/ hepatitis B virus (HBV) coinfection? In this setting, HCV is usually the main driver of viral activity, while HBV replication is suppressed. Because various studies have described HBV reactivation after HCV clearance, a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.

Keywords: Hepatitis C virus, Direct antiviral activity, Advanced cirrhosis, Liver cancer, Diabetes mellitus, Hepatitis C virus/hepatitis B virus coinfection.

Core Tip: The treatment of hepatitis C virus (HCV) infection has changed since direct-acting antivirals (DAAs) became available. DAA use has been extended to patients with advanced cirrhosis and severe comorbidities. Consequently, this review addresses the following questions: What benefits can be expected from eradicating HCV in patients who already have advanced liver disease? Are DAAs associated with an appreciable benefit in liver cancer? Can HCV treatment have favorable effects on the major concomitant disorders such as diabetes or cardiovascular disease? Is there any cause for concern when using DAAs in HCV patients with a concomitant hepatitis B virus infection?