Pentoxifylline vs. corticosteroid to treat severe alcoholic hepatitis: A randomised, non-inferiority, open trial

• Published in: Journal of hepatology 2014-10, Vol.61 (4), p.792-798
• Main Authors: Park, Seung Ha, Kim, Dong Joon, Kim, Young Seok, Yim, Hyung Joon, Tak, Won Young, Lee, Heon Ju, Sohn, Joo Hyun, Yoon, Ki Tae, Kim, In Hee, Kim, Hyoung Su, Um, Soon Ho, Baik, Soon Koo, Lee, June Sung, Suk, Ki Tae, Kim, Sang Gyune, Suh, Sang Jun, Park, Soo Young, Kim, Tae Yeob, Jang, Jae Young
• Format: Article
• Language: English
• Subjects: Adult; Alcoholic hepatitis; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Corticosteroid; Drug Monitoring; Female; Gastroenterology and Hepatology; Gastrointestinal Hemorrhage - etiology; Hepatitis, Alcoholic - complications; Hepatitis, Alcoholic - drug therapy; Hepatitis, Alcoholic - mortality; Hepatitis, Alcoholic - physiopathology; Hepatorenal Syndrome - etiology; Humans; Infection - etiology; Male; Middle Aged; Non-inferiority trial; Patient Selection; Pentoxifylline; Pentoxifylline - administration & dosage; Pentoxifylline - adverse effects; Phosphodiesterase Inhibitors - administration & dosage; Phosphodiesterase Inhibitors - adverse effects; Prednisolone - administration & dosage; Prednisolone - adverse effects; Severity of Illness Index; Survival Rate; Therapeutics
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2014.05.014

Background & Aims Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition. Methods In this multicentre, open-labelled, randomised non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddrey’s discriminant function ⩾32) to receive either pentoxifylline (400 mg, 3 times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone. Results The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those, taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, −4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (Δ15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs. 72.9%; p = 0.23). At 7 days, the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 59): 0.35 vs. 0.50 ( p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects, such as infection and gastrointestinal bleeding, were similar in the two groups. Conclusions The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.