Systematic Reviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2015; 21(6): 1972-1981
Published online Feb 14, 2015. doi: 10.3748/wjg.v21.i6.1972
Chronic hepatitis C genotype 1 treatment roadmap for resource constrained settings
Seng Gee Lim
Seng Gee Lim, Department of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Author contributions: Lim SG contributed to the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Seng Gee Lim, MBBS, MD, FRCP, FRACP, FAMS, Director of Hepatology, Department of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119228, Singapore. mdclimsg@nus.edu.sg
Telephone: +65-67724369 Fax: +65-67724361
Received: June 18, 2014
Peer-review started: June 19, 2014
First decision: July 9, 2014
Revised: July 21, 2014
Accepted: September 18, 2014
Article in press: September 19, 2014
Published online: February 14, 2015
Processing time: 238 Days and 4.3 Hours
Abstract

AIM: To use existing hepatitis C virus (HCV) antiviral therapies as access to new treatments is limited.

METHODS: A PubMed search for randomised control trials or meta-analysis related to response-guided therapy of HCV genotype 1 patients was undertaken using pegylated interferon and ribavirin (PR), boceprevir (B) and telaprevir (T) and lead-in where response-guided therapy at TW4(TW4), 8(TW8), 10(TW10), or 12(TW12) based on HCVRNA(+) or HCVRNA(-). Studies presented at major conferences were also used. Where necessary, a post-hoc analysis was performed. A response-guided management roadmap was created based on sustained virological response (SVR).

RESULTS: Starting with PR, those with HCVRNA(-) at TW4 have > 86% SVR, while those are HCVRNA(+) have 34%-41.7% SVR. HCVRNA(-) TW4 patients can have 24 wk PR if HCVRNA < 400000 IU/mL. Alternatively, 28 wk BPR has similar SVR. If HCVRNA(+) at TW4, 72 wk PR leads to 53% SVR, hence BPR is a better option, and if HCVRNA(-) by TW8, 28 wk therapy is sufficient. If HCVRNA(+) at TW8, then HCVRNA should be checked at TW10 and TW12. By TW12, HCVRNA ≥ 100 IU/mL activates the stopping rule. This roadmap is applicable for treatment-naïve, treatment failures and cirrhotic patients. Validation from an Asia Pacific early access boceprevir program confirmed the findings that HCVRNA(-) at TW4, or TW8 conferred > 80% SVR, leading to the “80-80” rule.

CONCLUSION: Using a roadmap based on HCVRNA(-) at TW4 or TW8 (the “80-80” rule), high SVR can be achieved, and guide the best choices for treatment, and also reduces drug exposure in poor responders.

Keywords: Chronic hepatitis C; hepatitis C virus RNA; Sustained virological response; Cirrhosis; Boceprevir; Telaprevir; Response-guided therapy; Peginterferon; Partial responder; Ribavirin

Core tip: Lex management of hepatitis C virus (HCV) genotype 1 using a simplified road map and "80-80" rule can help physicians manage their patients better. This roadmap distills the essential findings from using pegylated interferon and ribavirin as well as boceprevir using treatment week 4 and 8 virological responses based on whether HCVRNA is detectable or not.