Chandan Kumar Kedarisetty1,2, Ankit Bhardwaj3, Guresh Kumar3, Archana Rastogi4, Chhagan Bihari4, Manoj Kumar5, Shiv Kumar Sarin6. 1. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110 070, India. drchandankn@gmail.com. 2. Departments of Hepatology, Sri Ramachandra Institute of Higher Education and Research, Chennai 600 116, India. drchandankn@gmail.com. 3. Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi 110 070, India. 4. Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi 110 070, India. 5. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110 070, India. 6. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110 070, India. shivsarin@gmail.com.
Abstract
BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease. Vitamin E (VE), an anti-oxidant, has shown improvement in NAFLD activity score (NAS) but not fibrosis. Pentoxiphylline (PTX), an anti-TNF-alpha agent, has been reported to reduce hepatic inflammation and fibrosis. We evaluated combination of these drugs in NASH patients. METHODS: In a prospective study, consecutive histologically proven patients with NASH were randomized to receive either PTX, 400 mg thrice daily and VE 400 IU twice daily (group PTVE, n = 36) or VE alone (group VE, n = 33). Clinical, dietary and biochemical follow-up was done till 12 months. Primary end-point was change in alanine aminotransferase (ALT) levels. RESULTS: Both groups were comparable at baseline. On a strict diet and lifestyle modification regimen, both groups had similar reduction in body mass index and waist circumference. There was a similar reduction in ALT levels in the two groups. Metabolically, patients in PTVE group had greater reduction in fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) than VE group (p = 0.05). Tumor necrosis factor alpha (TNFα) levels were also significantly lower in PTVE group from 6 months onwards. Twelve (10%) patients had repeat liver biopsy (7 in group PTVE, 5 in group VE) with no difference in reduction of NAS score (p = 0.45). However, there was a significant fibrosis regression in PTVE compared to VE group (p = 0.003). CONCLUSIONS: These data show greater efficacy of a combination of PTX and VE in achieving fibrosis regression compared to VE alone with better metabolic homeostasis and amelioration of the pro-inflammatory status. TRIAL REGISTRATION: Clinical Trials Registry no. NCT01384578.
RCT Entities:
BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease. Vitamin E (VE), an anti-oxidant, has shown improvement in NAFLD activity score (NAS) but not fibrosis. Pentoxiphylline (PTX), an anti-TNF-alpha agent, has been reported to reduce hepatic inflammation and fibrosis. We evaluated combination of these drugs in NASH patients. METHODS: In a prospective study, consecutive histologically proven patients with NASH were randomized to receive either PTX, 400 mg thrice daily and VE 400 IU twice daily (group PTVE, n = 36) or VE alone (group VE, n = 33). Clinical, dietary and biochemical follow-up was done till 12 months. Primary end-point was change in alanine aminotransferase (ALT) levels. RESULTS: Both groups were comparable at baseline. On a strict diet and lifestyle modification regimen, both groups had similar reduction in body mass index and waist circumference. There was a similar reduction in ALT levels in the two groups. Metabolically, patients in PTVE group had greater reduction in fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) than VE group (p = 0.05). Tumor necrosis factor alpha (TNFα) levels were also significantly lower in PTVE group from 6 months onwards. Twelve (10%) patients had repeat liver biopsy (7 in group PTVE, 5 in group VE) with no difference in reduction of NAS score (p = 0.45). However, there was a significant fibrosis regression in PTVE compared to VE group (p = 0.003). CONCLUSIONS: These data show greater efficacy of a combination of PTX and VE in achieving fibrosis regression compared to VE alone with better metabolic homeostasis and amelioration of the pro-inflammatory status. TRIAL REGISTRATION: Clinical Trials Registry no. NCT01384578.
Authors: Han Ah Lee; Young Chang; Pil Soo Sung; Eileen L Yoon; Hye Won Lee; Jeong-Ju Yoo; Young-Sun Lee; Jihyun An; Do Seon Song; Young Youn Cho; Seung Up Kim; Yoon Jun Kim Journal: Clin Mol Hepatol Date: 2022-07-01