Hepatic granulomas: pathogenesis and differential diagnosis

Granulomatous liver disease constitutes a category of hepatic disorders and is at present diagnosed in approximately 4% of liver biopsies. Hepatic granulomas develop through the interactions of T lymphocytes and macrophages, with the integral involvement of T-helper (T(H)) 1 or T(H)2 pathways or both, depending on the specific granulomatous disease. Hepatic granulomas may be manifested clinically by elevated levels of serum alkaline phosphatase and g-glutamyltransferase enzymes, damage to specific structures (eg, intrahepatic bile ducts in primary biliary cirrhosis), or infrequently, progressive liver disease with portal hypertension and cirrhosis (eg, sarcoidosis). Systemic immunologic disorders, infectious diseases, drug hepatotoxicity, and reaction to neoplastic disease are the major causative factors responsible for granulomas in the liver. These causes and recent epidemiologic trends are covered in this discussion.