Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.4975
Peer-review started: December 1, 2014
First decision: December 26, 2014
Revised: January 16, 2015
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: April 28, 2015
AIM: To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis (AH).
METHODS: This study was an open-label clinical trial, performed at the “Hospital General de México, Dr. Eduardo Liceaga”. We randomized 135 patients who met the criteria for severe AH into the following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three times daily. The duration of the treatment for all of the groups was 30 d.
RESULTS: In the groups treated with the MTD, the survival rate was higher at 3 mo (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003) than in the groups not treated with MTD. A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo. The patients receiving MTD maintained greater abstinence than those who did not receive it (74.5% vs 59.4%, P = 0.02).
CONCLUSION: MTD improves the 3- and 6-mo survival rates in patients with severe AH. Alcohol abstinence is a key factor for survival in these patients. The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX.
Core tip: Severe alcoholic hepatitis (AH) has a high mortality rate. Oxidative stress and the depletion of mitochondrial glutathione are factors implicated in injury to the liver. Metadoxine (MTD), an antioxidant that participates in the synthesis of glutathione and inhibits hepatic lipid accumulation, appears to be a novel therapeutic agent in patients with severe AH because it improves their 3- and 6-mo survival. The patients who received MTD were also better able to abstain from alcohol use, which is a key factor contributing to the improved survival in patients with severe AH.