Journal of Hepatology zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 1999; 30:739-740 Printed in Denmark All rights reserved Munksgaard Copenhagen Copyright 0 European Association for the Study of the Liver 1999 Journal of Hepatology ISSN 0168-8278 Correspondence Treatment of alcoholic fatty liver: is the metabolic effect of metadoxine the only reason for improvedliver function? To the Editor: We read with interest the paper by Caballtria et al. which recently appeared in the Journal (1). After a double-blind randomized multi- centric study, the authors concluded that the improvement in steatosis and liver function tests observed in the metadoxine-treated group was due to the metabolic effect of the drug that accelerates ethanol and acetaldehyde catabolism. We observed a similar improvement in steatosis and liver function tests in alcoholic patients treated with gamma-hydroxybutyric acid, a drug which acts on GABA receptors in the hypothalamus and in the basal ganglia cells, with an anti-craving effect (2), but lacks the liver metabolic effect of metadoxine (3). Since metadoxine also has anti- craving properties (4,5), and a specific evaluation of abstinence was not reported in the study by Caballeria et al., the effect of metadoxine could merely be due to an undetected better compliance with alcohol abstinence in the treated group. Caution is warranted in attributing metabolic “protection” to a substance, because of the strong likelihood of misinterpretation and misuse by patients with alcohol abuse, who are always looking for a pretext not to stop drinking, which remains the only therapeutic chance for them. Giuseppe Francesco Stefanini’, Giovanni Addolorato2,3, Fabio Ca- puto3, Mauro Bernardi and Giovanni Gasbarrini2 ‘Department of Internal Medicine, Ospedale degli Infermi, Faenza. ‘In- stitute of Internal Medicine, UniversitLi Cattolica, Rome and 3 “G. Fon- tana” Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, University of Bologna, Bologna, Italy To the Editor: We would like to thank Dr Stefanini et al. for their interest in our paper published in the Journal (1). However, according to their letter, they have failed to understand the messages of our study. Thus, we would like to bring the following fatts to their atte’ntion: 1. Contrary to the statement of Dr. Stefanini et al., we did not conclude that the effect of metadoxine was merely due to a metabolic effect that accelerates ethanol and acetaldehyde catabolism. What we hypothesized in the paper as a mechanism.is that inetadoxine restores hepatic glutathione content and prevents the decrease in hepatic ATP concentration and, consequently, attempts to maintain the intracellu- lar redox homeostasis (2). It has also been demonstrated that meta- doxine accelerates the hepatic oxidation of ethanol and acetaldehyde (3) probably by the maintenance of normal levels of alcohol dehydro- genase during chronic ethanol intake (4). We stated in the paper that this former mechanism could explain the improvement in the sub- group of patients who did not remain total abstainers during the study. 2. Neither is the statement true that “a specific evaluation of absti- nence was not reported in the work by Caballeria et al”. By contrast, it is clearly mentioned in Patients and Methods that alcohol absti- References 1. Caballeria J, Pares A, Brd C, Mercader J, Plaza AG, Caballeria L, et al. and the Spanish Group for the Study of Alcoholic Fatty Liver. Metadoxine acelerates fatty liver recovery in alcoholic pa- tients: results of a randomized double-blind, placebo-controlled trial. J Hepatol 1998; 28: 54-60. 2. Addolorato G, Castelli E, Stefanini GF, Casella G, Caputo F, Marsigli L, et al. and GHB Study Group. An open multicentric study evaluating 4-hydroxybutyric acid sodium salt in the me- dium-term treatment of 179 alcohol-dependent subjects. Alcohol Alcohol 1996; 31: 341-5. 3. Viaggi M, Gentilini L, Zunarelli P Castelli E, Stefanini GF, Gas- barrini G. Tollerabilita epatica e sistemica dell’assunzione cronica di gamma-idrossibutirrolattone (GBL-OH). Alcologia 1990; 2: 272. 4. Annoni G, Khlat B, Lampertico P, Dell’Oca M, Dioguardi FS. Metadoxine (Metadoxil@) in alcoholic liver diseases. Clin Trial J 1988; 25: 33341. 5. Koch MM, Bazuro GE, Del Sette F, Dezi A, Ferrario F Fracasso PL et al. L’approccio al paziente alcolista in un ambulatorio di gastroenterologia: il possibile ruolo di un nuovo farmaco GABA agonista. Alcologia 1989; 1: 127-31. Reply nence during the treatment period was carefully controlled by ques- tioning the patient and relatives, and by serial urine alcohol determi- nation. As mentioned in the Results, we were able to identify 16 pa- tients in the metadoxine group and 15 patients in the placebo group who continued drinking. Furthermore, the alcohol intake during the study was significantly lower than initially and was similar in both groups (47.7?39 g/day in the metadoxine group and 57.3?31 g/day in the placebo group). Thus, it seems that the effect of metadoxine, as suggested by Stefanini et al., could not be due to “an undetected better compliance with alcohol abstinence in the treated group”. 3. We fully agree with Dr Stefanini et al. that alcohol abstinence is the first and most important therapeutic measure in patients with alcoholic liver disease, regardless of the severity. Our role as hepatol- ogists is to encourage our patients to start a detoxication program as soon as possible and, at the same time, to look for new and more effective specific treatments. Joan Caballeria (On behalf of the Spanish Group for the Study of Alcoholic Fatty Liver) Liver Unit, Hospital Clinic i Provincial, University of Barcelona, Spain 739