학술논문
Randomized Trial of Tenofovir With or Without Peginterferon Alfa Followed by Protocolized Treatment Withdrawal in Adults With Chronic Hepatitis B.
Document Type
Article
Author
Terrault, Norah A.; Lok, Anna S.; Wahed, Abdus S.; Ghany, Marc G.; Perrillo, Robert P.; Fried, Michael W.; Wong, David K.; Khalili, Mandana; Lau, Daryl T. Y.; Sterling, Richard K.; Di Bisceglie, Adrian M.; Lisker-Melman, Mauricio; Cooper, Stewart L.; Chung, Ray T.; Patel, Keyur; Roberts, Lewis R.; Belle, Steven H.; Janssen, Harry L. A.
Source
Subject
*TERMINATION of treatment
*HEPATITIS associated antigen
*CHRONIC hepatitis B
*HEPATITIS B virus
*TENOFOVIR
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Language
ISSN
0002-9270
Abstract
INTRODUCTION: Hepatitis B surface antigen (HBsAg) loss is associated with improved long-term outcomes of patients with chronic hepatitis B but is infrequently achieved with current monotherapies.We assessed whether combination strategies that included treatment withdrawal enhanced HBsAg loss. METHODS: A randomized (1:1) trial of tenofovir disoproxil fumarate (TDF) for 192 weeks with or without peginterferon (PegIFN) alfa-2a for the first 24 weeks, followed by withdrawal of TDF at week 192 with 48 weeks of off-treatment follow-up to week 240. The primary end point was HBsAg loss at week 240. RESULTS: Of 201 participants (52% HBeAg positive, 12%/6% genotype A/A2, 7% cirrhosis) randomized to TDF + PegIFN (n = 102) or TDF alone (n = 99), 6 participants had lost HBsAg at the end of the treatment phase (week 192), 5 (5.3%) in the combination group, and 1 (1.0%) in the TDF alone group (P = 0.09). By week 240, 9 participants had cleared HBsAg, 5.3% in combination, and 4.1% inmonotherapy arms (P50.73). HBsAg decline and loss occurred earlierwith TDF1 PegIFN than TDF, with a ≥1-logIU/mL qHBsAg decline by week 24 in28%in TDF + PegIFN compared with6%in TDF (P = 0.04). HBsAg loss occurred in 7 of 12 (58%) with hepatitis B virus subgenotype A2 (all HBeAg positive) compared with only 2 of 189 (1%) with other hepatitis B virus genotypes and in 8 of 93 (8.6%) HBeAg positive vs 1 of 87 (1.1%) HBeAg negative. DISCUSSION: PegIFN combined TDF followed by protocolized TDF withdrawal led to earlier but not higher percentages of HBsAg clearance. Pretreatment HBeAg positivity and subgenotype A2 were strongly associated with HBsAg clearance. [ABSTRACT FROM AUTHOR]