Nonalcoholic Fatty Liver Disease

The global obesity epidemic has dramatically increased the prevalence of NAFLD, which has become the most common cause of chronic liver disease in Western countries. NAFLD is considered the hepatic manifestation of the metabolic syndrome and shares a strong association with type 2 diabetes mellitus, obstructive sleep apnea, and cardiovascular disease. Although cardiovascular disease is the leading cause of death in patients with NAFLD, the subset of patients who meet histopathologic criteria for NASH are at greatest risk of liver-related morbidity and mortality. Ludwig and colleagues coined the term NASH in 1980 to describe a cohort of middle-aged patients with elevated serum liver enzyme levels who had evidence of alcohol-associated hepatitis on biopsy specimens in the absence of alcohol consumption. Subsequent study led to the proposed “2-hit” hypothesis in which a sequential progression from isolated fatty liver (IFL) to NASH involved the initial “hit” of hepatic steatosis followed by a second “hit” of oxidative stress, resulting in liver injury. Patients who have steatohepatitis on liver biopsy specimens are at greatest risk for progression to cirrhosis compared with those with IFL, and the 2-hit hypothesis has been modified to incorporate this observation. NASH is expected to become the most common cause for cirrhosis in the 2020s and is among the 3 most frequent indications for LT in the USA. As a growing public health concern, an understanding of the epidemiology and pathogenesis is paramount to facilitate our ability to effectively diagnose and treat patients with NAFLD and specifically NASH.