Antiviral Therapy for Chronic Hepatitis B with Mildly Elevated Aminotransferase: A Rollover Study from the TORCH-B Trial

Hsu, Yao-Chun; Chen, Chi-Yi; Tseng, Cheng-Hao; Chen, Chieh-Chang; Lee, Teng-Yu; Bair, Ming-Jong; Chen, Jyh-Jou; Huang, Yen-Tsung; Chang, I-Wei; Chang, Chi-Yang; Wu, Chun-Ying; Wu, Ming-Shiang; Mo, Lein-Ray; Lin, Jaw-Town

doi:.0..

Original Article

Antiviral Therapy for Chronic Hepatitis B with Mildly Elevated Aminotransferase: A Rollover Study from the TORCH-B Trial

Yao-Chun Hsu^1,2,15,16, Chi-Yi Chen³, Cheng-Hao Tseng^2,4, Chieh-Chang Chen⁵, Teng-Yu Lee^6,7, Ming-Jong Bair^8,9, Jyh-Jou Chen¹⁰, Yen-Tsung Huang¹¹, I-Wei Chang^12,13, Chi-Yang Chang^14,15, Chun-Ying Wu^16,17, Ming-Shiang Wu⁵, Lein-Ray Mo¹⁸, Jaw-Town Lin¹

¹Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan
²School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
³Division of Gastroenterology and Hepatology, Chia-Yi Christian Hospital, Chia-Yi, Taiwan
⁴Division of Gastroenterology and Hepatology, E-Da Cancer Hospital, Kaohsiung, Taiwan
⁵Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
⁶Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
⁷School of Medicine, Chung Shan Medical University, Taichung, Taiwan
⁸Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
⁹Mackay Medical College, New Taipei, Taiwan
¹⁰Department of Internal Medicine, Chi-Mei Medical Center, Liouying Branch, Tainan, Taiwan
¹¹Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
¹²Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
¹³Department of Clinical Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
¹⁴School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
¹⁵Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu-Jen Catholic University Hospital, Fu-Jen Catholic University, New Taipei, Taiwan
¹⁶Institute of Biomedical Informatics, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
¹⁷Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
¹⁸Department of Internal Medicine, Tainan Municipal Hospital, Tainan, Taiwan

Correspondence :

Yao-Chun Hsu ,
Email: holdenhsu@gmail.com
Jaw-Town Lin ,
Email: jawtown@gmail.com

Received: August 8, 2024 Revised: October 8, 2024 Accepted: October 15, 2024

ABSTRACT

Background & Aims
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

KeyWords: chronic hepatitis B; antiviral therapy; tenofovir disoproxil fumarate; TORCH-B trial