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World J Gastroenterol. Jun 21, 2014; 20(23): 7207-7212
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7207
When to stop nucleos(t)ide analogues treatment for chronic hepatitis B? Durability of antiviral response
Wonseok Kang, Jun Yong Park
Wonseok Kang, Jun Yong Park, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, South Korea
Wonseok Kang, Jun Yong Park, Liver Cirrhosis Clinical Research Center, Seoul 120-752, South Korea
Author contributions: Kang W and Park JY contributed to the concept and design of the study, literature search, analysis and interpretation of data and drafting of the manuscript; Park JY obtained funding and supervised the study.
Supported by Liver Cirrhosis Clinical Research Center, in part by a grant from the Korea Healthcare Technology R and D project, Ministry of Health and Welfare, Republic of Korea No. HI10C2020
Correspondence to: Jun Yong Park, MD, PhD, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea. drpjy@yuhs.ac
Telephone: +82-2-22281994 Fax: +82-2-3936884
Received: October 28, 2013
Revised: December 13, 2013
Accepted: January 14, 2014
Published online: June 21, 2014
Abstract

Introduction of nucleos(t)ide analogues (NAs) for oral antiviral therapy has dramatically improved the clinical outcome in patients with chronic hepatitis B (CHB). Although current international guidelines for the management of CHB provide information regarding when to begin the antiviral therapy with NAs, there is no clear consensus on when to stop the treatment, especially for those who respond to the therapy. Hepatitis B surface antigen loss has been regarded as an ideal endpoint of oral antiviral therapy with NAs, however since this is rarely achieved, practical endpoints have been suggested by the international guidelines. Despite the stopping rules recommended by the international guidelines, whether oral antiviral therapy with NAs can be safely discontinued is of major concern. While attention has been drawn to whether antiviral treatment with NAs can be a finite therapy, there is lack of sufficient data on off-treatment durability of highly potent NAs. Based on the available evidences, current guidelines for stopping NA therapy seems to be inadequate in terms of off-treatment durability, with relapse rates of more than 40% for both hepatitis Be antigen (HBeAg)-positive and HBeAg-negative patients. Therefore, further studies are required to accumulate data on off-treatment durability of highly potent NAs, and future studies are warranted to identify adequate predictive markers that could provide supplementary information to guide the timing of stopping NA therapy.

Keywords: Chronic hepatitis B, Antiviral therapy, Nucleos(t)ide analogue, Durability, Cessation

Core tip: Introduction of nucleos(t)ide analogues (NAs) for oral antiviral therapy has dramatically improved the clinical outcome in patients with chronic hepatitis B (CHB). While attention has been drawn to whether antiviral treatment with NAs can be a finite therapy in patients with CHB, current guidelines for stopping NA therapy seems to be inadequate in terms of off-treatment durability in both hepatitis Be antigen (HBeAg)-positive and HBeAg-negative patients. In the present work, we discussed the validity of current stopping rules of NA therapy and addressed areas of uncertainty in deciding the best timing to stop NA treatment.