Steatohepatitis (SH) is an intermediate stage of fatty liver disease and one of the most common causes of chronic liver disease worldwide that may progress to cirrhosis and liver cancer. SH encompasses alcoholic (ASH) and nonalcoholic steatohepatitis (NASH), the latter being of particular concern due to its association with obesity and insulin resistance and a major cause of liver transplantation. ASH is a major health concern of alcohol abuse and a leading cause of liver-related morbidity and mortality. The molecular mechanisms governing the transition from steatosis to SH are not fully understood. Recent evidence in ASH and NASH has indicated in that acid sphingomyelinase (ASMase), a specific mechanism of ceramide generation, is required for the activation of key pathways that regulate steatosis, fibrosis, insulin resistance and lipotoxicity, including endoplasmic reticulum (ER) stress, autophagy and lysosomal membrane permeabilization. The alcohol-induced ASMase-mediated ER stress was independent of the disruption of methionine metabolism and hyperhomocysteinemia caused by alcohol. Pharmacological inhibition of ASMase prevented alcohol-mediated ER stress, steatosis, and sensitization to LPS-mediated liver injury. These findings indicate that ASMase regulates multiple pathways and that its inhibtion may be of potential relevance in SH.

Comunicación presentada en el 9th International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis, celebrado del 21 al 23 de noviembre de 2014 en Szeged (Hungría), celebrado conjuntamente con el 3rd Annual Meeting od the Hungarian Pancreatic Study Group.

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