Case Report
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2018; 24(17): 1919-1924
Published online May 7, 2018. doi: 10.3748/wjg.v24.i17.1919
Development of tenofovir disoproxil fumarate resistance after complete viral suppression in a patient with treatment-naïve chronic hepatitis B: A case report and review of the literature
Woo Hee Cho, Hyun Jae Lee, Ki Bae Bang, Seok Bae Kim, Il Han Song
Woo Hee Cho, Hyun Jae Lee, Ki Bae Bang, Seok Bae Kim, Il Han Song, Department of Internal Medicine, Dankook University College of Medicine, Cheonan 31116, South Korea
Author contributions: Cho WH, Lee HJ and Bang KB collected the patient’s clinical data; Cho WH, Kim SB and Song IH designed the report and wrote the paper.
Informed consent statement: The patient was not required to give informed consent for this study because this study used clinical data that were obtained after this patient agreed to treatment but before treatment initiation.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.
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: Seok Bae Kim, MD, Professor, Department of Internal Medicine, Dankook University College of Medicine, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, South Korea. 11961019@dankook.ac.kr
Telephone: +82-41-5503910 Fax: +82-41-5563256
Received: March 21, 2018
Peer-review started: March 21, 2018
First decision: March 30, 2018
Revised: April 1, 2018
Accepted: April 15, 2018
Article in press: April 15, 2018
Published online: May 7, 2018
Abstract

Tenofovir disoproxil fumarate (TDF) is a potent nucleotide analogue that is recommended as first-line therapy for patients with chronic hepatitis B. The results of a longitudinal study of TDF treatment demonstrated no development of resistance. We observed one treatment-naïve chronic hepatitis B (CHB) patient who developed TDF resistance after complete viral suppression during long-term TDF treatment. A 37-year-old HBeAg-positive man received TDF 300 mg/d for 43 mo. The hepatitis B virus (HBV) DNA titer was 8 log10 copies/mL at baseline and became undetectable at 16 mo after treatment. However, the HBV DNA titer rebounded to 7.5 log10 copies/mL at 43 mo after treatment. We performed full sequencing to find mutation sites associated with virologic breakthrough. The results showed 9 mutation sites, most of which had not been well-known as mutation sites. We changed the therapy from tenofovir to entecavir with a regimen of 0.5 mg once daily. After 4 mo, the HBV DNA titer decreased to 267 copies/mL, and the liver enzyme levels were normalized.

Keywords: Chronic hepatitis B, Tenofovir, Resistance, Mutation

Core tip: The results of many clinical longitudinal studies of Tenofovir disoproxil fumarate (TDF) treatment have demonstrated no development of resistance until now. Recently, a few cases of resistance to TDF have been reported. However, the mutation site had not been clearly revealed and confirmed because of the rarity of resistant cases. In the present case, TDF resistance developed following the complete suppression of HBV DNA in a treatment-naïve patient. We detected 9 mutation sites, including some that have been unknown until now. We believe that the present study is helpful in revealing the exact mutation sites associated with TDF resistance.