Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of prevention and promising prospects for even more effective treatments. It continues to be important to replenish nutritional deficiencies when present but it is crucial to recognize that, because of the alcohol-induced disease process, some of the nutritional requirements change. For instance, methionine, one of the essential amino acids for humans, must be activated to SAMe but, in severe liver disease, the activity of the corresponding enzyme is depressed. Therefore, the resulting deficiencies and associated pathology can be attenuated by the administration of SAMe, but not by methionine. Similarly, phosphatidylethanolamine methyltransferase (PEMT) activity, which is important for hepatic phosphatidylcholine (PC) synthesis, is also depressed in alcoholic liver disease, therefore calling for administration of the products of the reaction. It might also be beneficial to add other compounds to such therapeutic regiment. Since free radical generation by the ethanol-induced CYP2E1 plays a key role in the oxidative stress, inhibitors of this enzyme have great promise. Several have been investigated experimentally and PPC is particularly interesting because of its innocuity. In view of the striking negative interaction between alcoholic liver injury and hepatitis C, an antiviral agent is eagerly awaited that, unlike Interferon, is not contraindicated in the alcoholic. Anti-inflamatory agents are also required. In addition to down-regulators of cytokines and end toxic are being considered. Finally, since excess drinking is the crux of the issue, anticraving agents should be incorporated in any contemplated therapeutic cocktail, in view of the recent promising results obtained with some of these agents such as naltrexone and acamprosate.
Beaucoup de progres ont ete realises dans la comprehension de la pathogenese de la maladie alcoolique du foie, ce qui a permis l'amelioration de la prevention et des perspectives prometteuses pour des traitements encore plus efficaces. Il reste important de combler les carences nutritionnelles lorsqu'elles existent, mais il est crucial de reconnatre que, a cause du processus meme de la pathologie alcoolique, certains besoins nutritionnels changent. Par exemple, la methionine, l'un des acides amines essentiels a l'homme, doit etre activee en S-adenosylmethionine (SAMe), mais dans le cas d'hepatopathie severe, l'activite de l'enzyme correspondante est diminuee. De ce fait, les carences resultantes et la pathologie associee peuvent etre attenuees par l'administration de SAMe, mais pas par celle de methionine. De la meme facon, l'activite de la phosphatidylethanolamine methyltransferase (PEMT), qui est importante pour la synthese de la phosphatidylcholine (PC) hepatique, est aussi reduite dans l'hepatopathie alcoolique, ce qui implique ainsi l'administration des produits de la reaction. Il serait egalement benefique d'ajouter d'autres composes a un tel regime therapeutique. Parce que la generation de radicaux libres par le CYP2E1 induit par l'alcool joue un role cle dans le stress oxydatif, les inhibiteurs de cette enzyme sont tres prometteurs. Plusieurs ont ete examines experimentalement et la PPC, qui est actuellement evaluee cliniquement, est particulierement interessante a cause de son innocuite. Etant donne l'interaction negative frappante entre la lesion hepatique alcoolique et l'hepatite C, on attend avec impatience un agent antiviral qui, contrairement a l'interferon, ne soit pas contre-indique chez l'alcoolique. Des agents anti-inflammatoires sont egalement necessaires. En plus des sterodes, sont pris en compte les regulateurs abaisseurs de cytokines et d'endotoxine. Enfin, parce que l'alcoolisation excessive est au centre de cette revue, des agents anti-craving devraient etre incorpores a chaque cocktail therapeutique envisage, etant donne les resultats prometteurs obtenus avec certains, tels que la naltrexone et l'acamprosate.