Less Common Causes of Hepatitis

Although metabolic, viral, and drug- and alcohol-related etiologies are a familiar part of the evaluation of elevated liver enzymes, less common causes include autoimmune hepatitis, Wilson disease, and hereditary hemochromatosis. Each has a progressive course to end-organ damage underscoring the importance of early recognition, as effective therapies are available. Autoimmune hepatitis is an immune-mediated liver disease, with a female predominance and autoantibodies present in about 80% of cases. It can progress rapidly without treatment. Liver biopsy featuring lymphoplasmacytic hepatitis is needed for diagnosis and to determine the intensity of immunosuppression. Wilson disease is caused by biallelic variants in the ATP7B gene resulting in copper accumulation in the liver, brain, kidneys, and corneas. Diagnosis relies on clinical findings, laboratory data, and genetic testing results. Lifelong chelation therapy is required. Hereditary hemochromatosis is characterized by iron overload, usually due to a common variant in the HFE gene with variable disease penetrance; it is prevalent in people of Northern European ancestry. Untreated hemochromatosis leads to cirrhosis and hepatocellular carcinoma. Early diagnosis and initiation of phlebotomy can result in normal life expectancy. To facilitate early diagnosis, genetic testing of first-degree relatives is recommended for those with Wilson disease or hemochromatosis.