Clinical Trials Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2015; 21(16): 4975-4985
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.4975
Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis
Fátima Higuera-de la Tijera, Alfredo I Servín-Caamaño, Aurora E Serralde-Zúñiga, Javier Cruz-Herrera, Eduardo Pérez-Torres, Juan M Abdo-Francis, Francisco Salas-Gordillo, José L Pérez-Hernández
Fátima Higuera-de la Tijera, Eduardo Pérez-Torres, Juan M Abdo-Francis, Francisco Salas-Gordillo, José L Pérez-Hernández, Liver Clinic, Gastroenterology Department, Hospital General de México, Dr. Eduardo Liceaga, Mexico City 06720, Mexico
Alfredo I Servín-Caamaño, Javier Cruz-Herrera, Internal Medicine Department, Hospital General de México, Dr. Eduardo Liceaga, Mexico City 06720, Mexico
Aurora E Serralde-Zúñiga, Fundación Mexicana para la Salud A.C, Mexico City 06720, Mexico
Author contributions: Higuera-de la Tijera F designed the study, provided financial support though the “Angeles Espinosa Yglesias 2010” stimulus, supervised the study, reviewed the statistical methods and wrote the final manuscript; Servín-Caamaño AI and Serralde-Zúñiga AE contributed to the acquisition, analysis and interpretation of the data and wrote the manuscript; Cruz-Herrera J, Pérez-Torres E, Abdo-Francis JM and Salas-Gordillo F contributed to the acquisition of data and cared for the patients; Pérez-Hernández JL reviewed the statistical methods and wrote the final manuscript; all of the authors read and approved the final manuscript.
Supported by Fatima Higuera-de la Tijera through the “Angeles Espinosa Yglesias 2010” stimulus granted by the FUNSALUD AC, AMPARO Foundation and FUNDHEPA AC, Mexico.
Ethics approval: The study was reviewed and approved by the “Hospital General de México, Dr. Eduardo Liceaga” Institutional Review Board.
Clinical trial registration: This study is registered at http://clinicaltrials.gov. The registration identification number is NCT02161653.
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: The authors have not conflict of interest to declare. None of the researchers involved in this study have received fees for serving as a speaker, consultant or as advisory board member for any organization.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at fatimahiguera@yahoo.com.mx. Consent for data sharing was not obtained but the presented data are anonymized and risk of identification is low. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Fátima Higuera-de la Tijera, MD, MSc, Liver Clinic, Gastroenterology Department, Hospital General de México, Dr. Eduardo Liceaga, Dr. Balmis 148, Mexico City 06720, Mexico. fatimahiguera@yahoo.com.mx
Telephone: +52-55-27892000
Received: November 28, 2014
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
Processing time: 150 Days and 6.3 Hours
Abstract

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.

Keywords: Alcoholic hepatitis; Metadoxine; Survival; Alcohol abstinence

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.