World Congress of Gastroenterology

WCOG 2019


 
TENOFOVIR FOR PREVENTING PROGRESSION OF CHRONIC HEPATITIS B IN PATIENTS WITH MINIMALLY RAISED AMINOTRANSFERASE (TORCH-B): A MULTICENTER RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL
YAO-CHUN HSU 1 Chi-Yi Chen 3 I-Wei Chang 4 Chi-Yang Chang 2 Chun-Ying Wu 6 Teng-Yu Lee 7 Ming-Shiang Wu 8 Ming-Jong Bair 9 Jyh-Jou Chen 10 Chieh-Chang Chen 8 Cheng-Hao Tseng 11 Chi-Ming Tai 1 Wen-Hui Ku 12 Lein-Ray Mo 13 Jaw-Town Lin 14

1- E-DA HOSPITAL/I-SHOU UNIVERSITY, KAOHSIUNG, TAIWAN
2- Fu-Jen Catholic University Hospital, New Taipei, Taiwan
3- Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
4- Taipei Medical University, Taipei, Taiwan
5- Taipei Veterans General Hospital, Taipei, Taiwan
6- National Yang-Ming University, Taipei, Taiwan
7- Taichung Veterans General Hospital, Taichung, Taiwan
8- National Taiwan University Hospital, Taipei, Taiwan
9- Taitung Mackay Hospital, Taiwan
10- Chi-Mei Medical Center, Tainan, Taiwan
11- E-DA Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
12- Taipei Institute of Pathology, Taipei, Taiwan
13- Tainan Municipal Hospital, Tainan, Taiwan
14- China Medical University Hospital, Taichung, Taiwan
 
Background/Aims:

Chronic hepatitis B (CHB) is the leading cause of liver-related morbidity and mortality worldwide. Antiviral therapy is currently recommended for patients with CHB at advanced disease status. Whether treatment can prevent disease progression in patients with minimally raised alanine aminotransferase (ALT) is unclear.

Materials and Methods:

 In this multicentre, double-blind, placebo-controlled trial, we randomly assigned CHB patients without liver cirrhosis, who presented with viremia above 2,000 IU/mL and ALT elevation between 1~2 folds the upper limit of normal, to receive tenofovir disoproxil fumarate (TDF) or matching placebo for 3 years. The primary outcomes were histological deterioration (≥2-point increase in Knodell necroinflammatory score or any worsening of fibrosis) and fibrosis progression (any increase in Ishak scale). We also explored virological, biochemical, serological outcomes and adverse events. 

Results:

From January 2012 to November 2015, 79 and 81 patients were randomized to TDF and placebo, respectively. After 3-year treatment, 146 patients (n=73 in each group) completed the trial with paired liver biopsy. Histological deterioration occurred in 31.5% (n=23) and 57.5% (n=42) in the TDF and placebo group, respectively (P=0.03). The relative risk of TDF for histological deterioration was 0.55 (95% CI, 0.37~0.81). Liver fibrosis progressed in 26.0% (n=19) and 46.6% (n=34) in the TDF and placebo group, respectively (P=0.02). The relative risk for fibrosis progression was 0.56 (95% CI, 0.35~0.88). TDF achieved higher rates of viral and biochemical remission but the two groups were similar in serological outcomes. More patients in the placebo group (16.1% vs. 2.5%, P=0.005) experienced hepatitis events that required rescue therapy.

Conclusion:

Antiviral therapy prevents histopathological progression in non-cirrhotic CHB patients who present with minimally raised ALT and significant viremia.

Keywords:

 HBV; TDF; nucleos(t)ide analogue; oral antiviral therapy; TORCH-B