Hepatitis, Autoimmune

Key Features

Essentials of Diagnosis

• Acute or chronic hepatitis

• Hypergammaglobulinemia

• Positive antinuclear antibodies (ANA), anti–smooth muscle antibodies (ASMA), anti–liver-kidney microsomal (LKM) antibodies, anti-actin antibodies, or anti–soluble liver antigen antibodies (SLA)

General Considerations

• Progressive inflammatory disorder of unknown etiology

• Characterized histologically by portal tract inflammation that extends into the parenchyma; serologically by the presence of nonorgan-specific autoantibodies; biochemically by elevated aminotransferases and serum IgG; and clinically by response to immunosuppressive treatment in the absence of other known causes of liver disease

• A family history of autoimmune diseases is present in approximately 40% of cases

Clinical Findings

Symptoms and Signs

• Often asymptomatic early in the disease process

• Lethargy as well as malaise

• Jaundice

• Recurrent fevers

• Abdominal pain or distention

• Other complaints at the time of presentation may include

  • Recurrent rash

  • Arthritis

  • Chronic diarrhea

  • Amenorrhea

• Hepatomegaly or splenomegaly may be found on examination

• In more advanced cases, jaundice and ascites may develop

• Cutaneous signs of chronic liver disease may be noted

  • Spider angiomas

  • Palmar erythema

  • Digital clubbing

Differential Diagnosis

• Hepatitis B

• Hepatitis C

• Steatohepatitis

• Wilson disease

• α₁-Antitrypsin deficiency

• Primary sclerosing cholangitis

• Drug-induced chronic hepatitis

Diagnosis

Laboratory Findings

• Moderate elevations of serum AST, ALT

• Variable elevations of alkaline phosphatase, bilirubin, and total IgG

• Liver biopsy

  • Remains the gold standard in diagnosis

  • Reveals the typical histologic picture of interface hepatitis

Treatment

• Corticosteroids (prednisone, 2 mg/kg/d maximum 60 mg) as induction therapy decreases the mortality rate during the early active phase of the disease

• Azathioprine or 6-mercaptopurine (6-MP), 1–2 mg/kg/d, as maintenance therapy

  • Valuable in decreasing the side effects of long-term corticosteroid therapy

  • Should not be used alone during the induction therapy

• Thiopurine methyltransferase activity in red blood cells or genotype should be assessed prior to starting azathioprine or 6-MP to prevent extremely high blood levels and severe bone marrow toxicity

• In type 1 autoimmune hepatitis

  • Corticosteroids are reduced over a 3- to 6-month period

  • Azathioprine is continued for at least 1–2 years

  • If AST and ALT have been consistently normal, tapering therapy can be considered

  • Liver biopsy must be performed before stopping azathioprine or 6-MP therapy; if any inflammation persists, then azathioprine or 6-MP is continued

  • Most pediatric patients require long-term azathioprine or 6-MP therapy

  • Relapses are treated with a course of corticosteroids

• In type 2 autoimmune hepatitis, patients must continue taking azathioprine and low-dose corticosteroids

• Cyclosporine, tacrolimus, or methotrexate may be helpful in poorly responsive cases

• Mycophenolate mofetil can be substituted for azathioprine or 6-MP

• Liver transplantation indications

  • Disease progresses to decompensated cirrhosis

  • Acute liver failure that does not respond to corticosteroid therapy

Outcome

Complications

• Untreated ...