This patient with jaundice, hepatomegaly, elevated transaminases, and high anti–smooth muscle antibody titers most likely has autoimmune hepatitis (AIH).  AIH occurs most commonly in women with other autoimmune conditions (eg, type 1 diabetes mellitus).  It is often asymptomatic but may present with fatigue, weight loss, nausea, and/or signs of acute hepatitis (eg, jaundice, abdominal discomfort).  Characteristic laboratory abnormalities include a hepatocellular pattern of liver injury (ie, predominant transaminase elevation with normal alkaline phosphatase and variable bilirubin) and the formation of a variety of autoantibodies, particularly anti–smooth muscle, which is highly specific for AIH.  Hypergammaglobulinemia is also typical.

The pathogenesis of AIH is incompletely understood but likely involves exposure to an environmental trigger in genetically predisposed patients, leading to regulatory T-cell dysfunction.  It ultimately results in loss of self-tolerance, with an immune response against hepatic antigens.  This is demonstrated histologically by lymphocyte and plasma cell infiltration of portal and periportal regions of the liver.

(Choice A)  Chronic hepatitis B is characterized histologically by ground-glass hepatocytes, which result from the accumulation of hepatitis B surface antigen within their cytoplasm, as well as central balloon degeneration, which reflects hepatocytes undergoing apoptosis.

(Choice B)  Hepatic steatosis (ie, lipid accumulation in the cytoplasm of hepatocytes) and ballooning degeneration most commonly occur in alcohol-induced hepatitis and nonalcoholic fatty liver disease.  Elevated anti–smooth muscle antibody titers do not occur.

(Choice C)  Acetaminophen overdose can lead to hepatic inflammation and necrosis with neutrophilic infiltration (unlike AIH, which is characterized by lymphoplasmocytic infiltrates).  Patients often have vomiting, diaphoresis, and confusion.

(Choice D)  Primary sclerosing cholangitis causes periductal fibrosis and luminal obliteration of the biliary ducts, which can lead to cholestasis.  High alkaline phosphatase levels and near-normal aminotransferases are expected.

Educational objective:
Autoimmune hepatitis results from an immune response against hepatic antigens, leading to a lymphoplasmacytic infiltrate in the portal and periportal regions of the liver.  Manifestations include fatigue, weight loss, nausea, and/or signs of acute hepatitis (eg, jaundice, abdominal discomfort).  Characteristic laboratory abnormalities include a hepatocellular pattern of liver injury, anti–smooth muscle autoantibodies, and hypergammaglobulinemia.