Pathogenesis and pathways: nonalcoholic fatty liver disease & alcoholic liver disease

Abstract

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) account for the majority of hepatic morbidity and deaths due to cirrhosis in the United States. ALD is an umbrella term for a number of conditions linked to excessive alcohol consumption including simple steatosis, cirrhosis, acute alcoholic hepatitis (AH) with or without cirrhosis, and hepatocellular carcinoma (HCC) as a complication of cirrhosis. Although it presents with histological features resembling alcohol-induced liver injury, NAFLD occurs in patients with little or no history of alcohol consumption. NAFLD is a broad-spectrum term used to describe anything from fat accumulation in hepatocytes without inflammation or fibrosis (simple hepatic steatosis) to hepatic steatosis with a necroinflammatory component (steatohepatitis) with or without associated fibrosis. The pathogenesis is not fully understood for either disease. Development of severe liver disease is highly variable amongst chronic abusers of alcohol. Sex, age, genetics, host microbiome, and behavior are all factors linked to the development of ALD. These factors also contribute to NAFLD, but by contrast, insulin resistance is widely believed to be the main driver of nonalcoholic hepatic steatosis. The mechanism behind the transition from nonalcoholic steatosis to steatohepatitis remains a matter of debate with insulin resistance, oxidative injury, hepatic iron, gut hormones, antioxidant deficiency, and host microbiome all suspected to play part of the role.

Keywords: Alcohol; alcoholic hepatitis (AH); fibrosis; liver; portal hypertension.