Pathophysiological similarities and synergisms in alcoholic and non-alcoholic steatohepatitis.

Chronic alcohol consumption is one of the main etiological factors for liver disease worldwide, however only a fraction of drinkers develop significant hepatic inflammation (alcoholic steatohepatitis), and even less progress to significant hepatic fibrosis and cirrhosis. The pathophysiological significance of hepatic lipid accumulation in the absence of significant alcohol consumption is also increasingly recognized. Non-alcoholic fatty liver disease (NAFLD) is regarded as the hepatic manifestation of the metabolic syndrome, and it is the most common cause of liver enzyme elevations in Western countries. Similarly to alcoholic liver disease, NAFLD encompasses mild hepatic steatosis to non-alcoholic steatohepatitis with significant necroinflammation and progressive fibrosis. Several clinical studies suggest a strong causative link between the consumption of alcohol and progressive liver disease in individuals with high fat intake and/or diabetes. However, it is incompletely understood how alcohol and obesity interact and whether the combined effects on the progression of liver injury are additive or synergistic. This review describes single as well as combined effects of alcohol and (components of) the metabolic syndrome on hepatic steatosis, inflammation and fibrosis. In addition to direct effects on the liver, the view is expanded to other organs affected by chronic alcohol consumption or the metabolic syndrome, to understand also extrahepatic pathophysiological mechanisms involved in hepatocellular injury. Undoubtedly, alcohol and the metabolic syndrome appear as a dangerous mix, and there are important synergistic effects of either condition with regard to crucial triggers of liver injury.