title: Treatment with metadoxine and its impact on early mortality in patients with severe alcoholic hepatitis.
abstract: OBJECTIVE
  Despite treatment with glucocorticoids, mortality remains high in patients with severe alcoholic hepatitis. Oxidative stress and depletion of mitochondrial glutathione are implicated factors in liver injury. The aim of this study was to evaluate the impact of the addition of metadoxine, a drug which possesses a multifactorial mechanism of action, including antioxidant properties, to standard treatment with glucocorticoids in patients with severe alcoholic hepatitis.
  
  
  METHODS
  This randomized open label clinical trial was performed in Mexico's General Hospital (Registry Key DIC/10/107/03/043). We randomized 70 patients with severe alcoholic hepatitis. The first group received prednisone (40 mg/day), and the second group received prednisone (40 mg/day) plus metadoxine tablets (500 mg three times daily). The duration of treatment in both groups was 30 days. Survival at 30 and 90 days, development of complications, adverse events and response to treatment (Lille model) were assessed.
  
  
  RESULTS
  In the group receiving metadoxine, significant improvements were observed, as follows: survival at 30 days (74.3 vs. 45.7%, P = 0.02); survival at 90 days (68.6 vs. 20.0%, P = 0.0001). There was less development or progression of encephalopathy (28.6 vs. 60.0%, P = 0.008) and hepatorenal syndrome (31.4 vs. 54.3%, P = 0.05), and the response to treatment (Lille model) was higher in the metadoxine group (0.38 vs. 0.63, P = 0.001; 95% CI 0.11 to 0.40). There were no differences between groups regarding the development or progression of variceal hemorrhage or infection. The incidence of adverse events, mainly gastrointestinal, was similar in both groups.
  
  
  CONCLUSIONS
  Addition of metadoxine to glucocorticoid treatment improves the short-term survival of patients with severe alcoholic hepatitis and diminishes the development or progression of encephalopathy and hepatorenal syndrome.
authors.affiliation: Gastroenterology Department, Hospital General de México, México.
authors.forename: Fátima
authors.initials: F
authors.lastname: Higuera-de la Tijera
authors.affiliation: Internal Medicine Department, Unit 108, Hospital General de México, México.
authors.forename: Alfredo I
authors.initials: AI
authors.lastname: Servín-Caamaño
authors.affiliation: Internal Medicine Department, Unit 108, Hospital General de México, México.
authors.forename: Javier
authors.initials: J
authors.lastname: Cruz-Herrera
authors.affiliation: Fundación Mexicana para la Salud A.C., México.
authors.forename: Aurora E
authors.initials: AE
authors.lastname: Serralde-Zúñiga
authors.affiliation: Gastroenterology Department, Hospital General de México, México.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Abdo-Francis
authors.affiliation: Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Facultad de Medicina, Universidad Nacional Autónoma de México, México.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gutiérrez-Reyes
authors.affiliation: Gastroenterology Department, Hospital General de México, México.
authors.forename: José L
authors.initials: JL
authors.lastname: Pérez-Hernández
mesh_terms: D000328:Adult; D000368:Aged; D000427:Alcohol Deterrents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004932:Esophageal and Gastric Varices / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control; D005938:Glucocorticoids / Q000627:therapeutic use*; D006501:Hepatic Encephalopathy / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D006519:Hepatitis, Alcoholic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006530:Hepatorenal Syndrome / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D011736:Pyridoxine / Q000627:therapeutic use*; D011761:Pyrrolidonecarboxylic Acid / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000427:Alcohol Deterrents; D000975:Antioxidants; D004338:Drug Combinations; D005938:Glucocorticoids; C037845:metadoxine; D011736:Pyridoxine; D011761:Pyrrolidonecarboxylic Acid; D011241:Prednisone