Secondary causes of fatty liver disease - an update on pathogenesis, diagnosis and treatment strategies

Secondary causes of fatty liver disease are important to recognize since specific therapy options are available for some of these causes. Common causes of secondary fatty liver disease comprise hepatitis C virus infection (HCV), endocrinological diseases, nutritional and intestinal diseases as well as genetic liver and metabolic diseases. Certain drugs may also predispose to the development of fatty liver disease. Primary fatty liver disease, also known as non-alcoholic fatty liver disease (NAFLD) is defined by the presence of steatosis hepatis without relevant alcohol consumption or other causes of secondary fatty liver disease. NAFLD occurs more frequently in patients with metabolic syndrome and thus can be seen as the hepatic manifestation of the metabolic syndrome. Therefore, presence of features of the metabolic syndrome should be assessed in all patients with fatty liver disease. Furthermore, alcohol consumption should be determined to rule out alcoholic liver disease (ASH). Further diagnostic work up for secondary causes of fatty liver disease should include screening for HCV infection, for hypothyroidism and for drugs associated with steatosis development. In a next step screening for Wilson's disease, hemochromatosis, celiac disease and lipid metabolism disorders should be performed. An extended endocrinological workup and a liver biopsy should be considered if the etiology of fatty liver disease remains unclear. Common genetic polymorphisms have been identified in several genes, such as PNPLA3, TM6SF2 and MBOAT7, which may promote the development and the progression of fatty liver disease irrespective of the underlying etiology (e. g. metabolic syndrome, ASH or HCV). The risk variants in these genes have additive effects on steatosis development and diseases progression towards fibrosis and cirrhosis. The diagnosis of secondary causes of fatty liver disease may allow for therapeutic intervention and prevent disease progression. Accordingly, secondary causes of fatty liver disease should be considered during the diagnostic workup of NAFLD patients.