Autoimmune Hepatitis

Autoimmue Hepatitis (AIH) is a chronic unresolving inflammation of the liver. Cause not known. Associated with circulating autoantibodies and hypogammaglobulinemia.

Classifcation: Two types of AIH

Type I AIH: most common form of the disease worldwide, associated with ANAs and antismooth muscle antibodies (SMAs).

Type II AIH: characterized by autoantibodies to liver/kidney microsome types (anti LKM1). Seen predominantly in children and young adults.

AIH with antibodies to soluble liver antigen/liver pancreas (anti-SLA/LP)

Epidemiology:

AIH occurs worldwide.

Common in white North Europeans

Accounts for ~6% of liver transplantation in the U.S.

Women affected > men (3:1)

Cirrhosis is present at initial presentation more often in African American patients than Caucasian patients.

Associated with extrahepatic manifestations: In 30% to 50% of cases, includes: celiac disease, Coomb's positive hemolytic anemia, autoimmune thyroiditis, Graves' disease, RA, ulcerative colitis.

Dx: Acute presentation similar to viral hepatitis. Fulminant liver failure (FHF) or with asymptomatic elevations of serum ALT. It presents with cirrhosis in at least 25% cases.

History: fatigue, jaundice, mylagias, anorexia, diarrhea, acne, and RUQ abdominal discomfort. Pts with AIH may overlap with findings consistent with other liver diseases (PBC, PSC, and autoimmune cholangitis)

PE: Nonspecific exam.

Diagnostic testing: Liver bx is essential to dx.

Piecemeal necrosis or interface hepatitis with lobular or panacinar inflammation (lymphocytic and plasmacytic infiltration) are the histologic hallmarks of the disease.

Histologic change, such as ductopenia or destructive cholangitis, may indicate overlap syndromes combining characteristic AIH, PBC, PSC, or autoimmune cholangitis)

Tx:

First line: prednisone, 40-60 mg daily or in combination of azathioprine 1-2 mg/kg/d. Prednisone is tapered with biochemical and clinical improvement to an eventual d/c of tx. Some Pts need lifelong low-dose therapy.

Second line: Refractory disease (remission not achieved with first-line therapy) may need "salvage" therapy with cyclosporine, tacrolimus, or mycophenolate mofetil.

Surgical management: Liver transplantation should be considered in Pts with ESLD.

After transplantation, recurrent AIH is seen in ~15% of Pts. De novo AIH or immunologically mediated hepatitis, defined as hepatitis with histologic features similar to AIH in Pts transplanted for nonautoimmune diseases, described in ~5% of transplant recepients.

F/up: 90% have improvement in AST, bilirubin, and gamma-globulin levels within 2 wks of Tx. Histologic improvement lags behind clinical and lab improvement by 3-6 months.

Remission is achieved in 65%-80% cases within 1.5 - 3 years, of treatment respectively.

Relapses occur in nearly 20%-50% of Pts, after stopping Tx. Relapses require tx.