Autoimmune liver diseases

Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are three distinct autoimmune liver diseases. Immunoglobulin G4 (IgG4) associated cholangitis is another immune disorder which mimics PSC and is characterized by formation of biliary strictures responsive to steroid therapy. The simultaneous or successive coexistence of PBC and AIH or PSC and AIH is called overlap syndrome. AIH is a chronic inflammatory immune-mediated liver disease characterized by elevated transaminase levels, hypergammaglobulinemia and histological features of interface hepatitis. The diagnosis of AIH is based on the scoring systems of the International Autoimmune Hepatitis Group (IAIHG) after exclusion of other causes of chronic liver disease. AIH is treated with prednisone alone or in combination with azathioprine and both strategies are equally effective. PBC and PSC are both chronic cholestatic liver diseases with slowly progressive courses. Fatigue and pruritus are the most common symptoms but the majority of the patients at first presentation are asymptomatic. The diagnostic criteria for PBC include serum alkaline phosphatase levels at least twice the upper limit of normal and a positive test for serum antimitochondrial antibodies. A liver biopsy specimen showing inflammatory changes involving the bile duct supports the diagnosis but is not mandatory. Ursodeoxycholic acid is the only FDA-approved therapy for PBC in a dose of 13-15mg/kg/day. PSC is most commonly diagnosed with endoscopic retrograde cholangiopancreatography (ERCP), although magnetic resonance cholangiography (MRC) is rapidly emerging as the first-choice diagnostic test. There is no effective medical treatment for PSC and liver transplantation is the only life extending therapy for end-stage disease. IgG4 associated cholangitis is an immune disorder characterized by formation of biliary strictures and frequently involves extrahepatic bile ducts. It is often associated with other autoimmune disorders such as autoimmune pancreatitis. The serum level of IgG4 is usually elevated and there is infiltration of IgG4 positive plasma cells in bile ducts. Clinically, patients present with abrupt onset jaundice which responds to steroid therapy. Pathogenesis and standard diagnostic criteria for the overlap syndrome have not yet been established. In this review we discuss in detail the clinical presentation, pathogenesis, diagnosis and treatment of AIH, PBC, PSC, IgG4 associated cholangitis and overlap syndromes.