An expert review on the use of tenofovir alafenamide for the treatment of chronic hepatitis B virus infection in Asia
Michael R Charlton 1 , Altaf Alam 2 , Akash Shukla 3 , Bekhbold Dashtseren 4 , Cosmas Rinaldi Adithya Lesmana 5 , Davadoorj Duger 6 , Diana Alcantara Payawal 7 , Do Duy Cuong 8 , Ganbolor Jargalsaikhan 9 10 11 , Ian Homer Yee Cua 12 , Jose Decena Sollano 13 , Karam Romeo Singh 14 , Kaushal Madan 15 , Khin Maung Win 16 , Khin Pyone Kyi 17 , Kyaw Soe Tun 18 , Mohd Salih 19 , Mukul Rastogi 20 21 , Neeraj Saraf 22 , Pham Thi Thu Thuy 23 , Pham Tran Dieu Hien 24 , Rino Alvani Gani 25 , Rosmawati Mohamed 26 , Tawesak Tanwandee 27 , Teerha Piratvisuth 28 , Wattana Sukeepaisarnjaroen 29 , Win Naing 30 , Zahid Yasin Hashmi 31
Affiliations
Affiliations
1
Transplant Institute, Center for Liver Diseases, University of Chicago Biological Sciences, 5841 South Maryland Avenue, Chicago, Illinois, USA. [email protected].
2
GI Hepatology, Lahore, Pakistan.
3
Department of Gastroenterology, LTM Medical College and Sion Hospital, Maharashtra, Mumbai, India.
4
Liver Center Hospital, Ulaanbaatar, Mongolia.
5
Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia.
6
Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia.
7
Department of Medicine, Cardinal Santos Medical Center, Mandaluyong, Metro, Manila, Philippines.
8
Department of Infectious Diseases and HIV Outpatient Clinic, Bach Mai Hospital, Hanoi, Vietnam.
9
Department Liver Center, Ulaanbaatar, Mongolia.
10
Department International Graduate Program in Medicine (IGPM) Institution, Ulaanbaatar, Mongolia.
11
College of Medicine, Taipei Medical University, Taipei, Taiwan.
12
Research Committee and Social Committee, Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Taguig, Philippines.
13
Department of Medicine, University of Santo Tomas Hospital, Manila, Philippines.
14
Liver Clinic, Regional Institute of Sciences, Imphal, India.
15
Gastroenterology & Hepatology, Max Smart Super Speciality Hospital, Saket, New Delhi, India.
16
University of Medicine (1) YGN, Yangon, Myanmar.
17
Myanmar Liver Foundation, Liver Foundation, Yangon, Myanmar.
18
Myanmar GI and Liver Society, Yangon, Myanmar.
19
Department of Hepatology, Quaid e Azam International Hospital, Islamabad, Pakistan.
20
Department of Hepatology and Gastroenterology, Fortis Hospital, Noida, India.
21
Department of Transplant Hepatology, Fortis Hospital, Noida, India.
22
Clinical/Transplant Hepatology Institute of Digestive and Hepatobiliary Sciences Medanta, The Medicity, Gurgaon, New Delhi, India.
23
Department of Medic Medical Center, Ho Chi Minh City, Vietnam.
24
Department of Infectious Disease, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam.
25
Liver Transplantation team, Ciptomangunkusumo Hospital, Jakarta, Indonesia.
26
Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
27
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
28
Department of Medicine, NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand.
29
Gastroenterology Unit, Department of Medicine, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
30
Department of Hepatology, Yangon General Hospital, University of Medicine (1), Yangon, Myanmar.
31
PMC, Allied and DHQ Hospital, Faisalabad, Pakistan.
PMID: 32666200 DOI: 10.1007/s00535-020-01698-4
Abstract
Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for curbing HBV infection and associated morbidity in Asia. However, there are some challenges to the use of ETV and TDF; while ETV is associated with high resistance in lamivudine (LAM)-exposed (especially LAM-refractory) patients; bone and renal safety issues are a major concern with TDF. Hence, a panel of twenty-eight expert hepatologists from Asia convened, reviewed the literature, and developed the current expert opinion-based review article for the use of TAF in the resource-constrained settings in Asia. This article provides a comprehensive review of two large, phase 3, double-blind, randomized controlled trials of TAF versus TDF in HBeAg-negative (study 0108) and HBeAg-positive (study 0110) chronic HBV patients (> 70% Asians). These studies revealed as follows: (1) non-inferiority for the proportion of patients who had HBV DNA < 29 IU/mL; (2) significantly high rate of normalization of alanine aminotransferase levels; (3) no incidence of resistance; and (4) significantly better bone and renal safety, with TAF vs. TDF up to 144 weeks. Considering the benefits of TAF, the expert panel proposed recommendations for optimizing the use of TAF in Asia, along with guidance on specific patient groups at risk of renal or bone disease suitable for TAF therapy. The guidance provided in this article may help clinicians optimize the use of TAF in Asia.
亚洲的乙型肝炎病毒（HBV）感染率处于中到高的发病率和高发病率。使用抗药性高的指南推荐的核苷酸类似物，例如恩替卡韦（ETV），替诺福韦二吡呋酯富马酸酯（TDF）和替诺福韦阿拉芬酰胺（TAF），是遏制HBV感染的关键干预措施之一，亚洲的相关发病率。但是，使用ETV和TDF面临一些挑战。拉美夫定（LAM）暴露（尤其是LAM难治性）患者的ETV与高耐药性相关；骨和肾脏安全问题是TDF的主要关注点。因此，由来自亚洲的28位专家肝病专家组成的小组召集，审查了文献，并撰写了当前基于专家意见的评论文章，供在亚洲资源有限的地区使用TAF。本文对HBeAg阴性（研究0108）和HBeAg阳性（研究0110）的慢性HBV患者（> 70％亚洲人）中的TAF与TDF进行的两项大型，三阶段，双盲，随机对照试验进行了全面回顾。这些研究表明：（1）HBV DNA <29 IU / mL的患者的比例不逊色； （2）丙氨酸氨基转移酶水平的正常化率极高； （3）无耐药性发生； （4）在144周内，TAF与TDF相比，明显改善了骨骼和肾脏的安全性。考虑到TAF的益处，专家小组提出了在亚洲优化TAF使用的建议，并针对有可能患TAF治疗的有肾病或骨病风险的特定患者群体提供了指导。本文提供的指南可帮助临床医生在亚洲优化TAF的使用。