Hyung Joon Yim1, Won Kim2, Sang Hoon Ahn3, Young Kul Jung1, Soon Ho Um1, Joo Hyun Sohn4, Jae Young Jang5, Dong Joon Kim6, Eun-Sook Park7, So-Young Jin8, Kyun-Hwan Kim9. 1. Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. 2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea. 3. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea. 5. Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Republic of Korea. 6. Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea. 7. Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea. 8. Department of Pathology, Soonchunhyang University College of Medicine, Seoul, Republic of Korea. 9. Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon, Republic of Korea.
Abstract
BACKGROUND AND AIM: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. METHODS: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. RESULTS: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). CONCLUSIONS: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients.
BACKGROUND AND AIM: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. METHODS: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. RESULTS: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). CONCLUSIONS: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients.
Authors: Jong Chul Kim; Hye Young Lee; Ah Ram Lee; Mehrangiz Dezhbord; Da Rae Lee; Seong Ho Kim; Juhee Won; Soree Park; Na Yeon Kim; Jae Jin Shin; Sang Gyune Kim; Young Seok Kim; Jeong-Ju Yoo; Kyun-Hwan Kim Journal: Biomedicines Date: 2022-01-26