Treatment Strategies for Autoimmune Hepatitis

Some while after the entity “autoimmune hepatitis” (AIH) was first recognized in the late 1950s, it was realized that patients with this disease may present with diverse disease manifestations ranging from acute fulminant hepatic failure to asymptomatic disease. Thus the typical presentation originally described, of a young woman with malaise, secondary amenorrhea, arthralgia, and jaundice is far from universal. This disease may affect individuals of all ages although presentation with burned out cirrhosis with evidence of liver failure is more typically seen in older patients. In children and young adults particularly, it is now appreciated that AIH commonly exists concurrently with primary sclerosing cholangitis (PSC). A recent report suggests that routine magnetic resonance cholangiography in 78 consecutive adult patients with AIH indicated that 10% had an abnormal magnetic resonance cholangiogram (MRC). STEPS IN THE MANAGEMENT OF AIH AIH is a lifelong disease; hence it is very important to make a confident diagnosis at the time of initial presentation. If there are any doubts, application of the AIH scoring system may facilitate the diagnosis (2). When to start therapy may be another difficult decision. Whatever therapeutic plan is decided needs to be discussed with the affected individual. It is essential the patient understands the natural history of AIH and the preventative strategies that need to be taken. Only with adequate education will the patient realize the importance of long-term follow-up. AIH SCORING SYSTEM This score was designed by an international group of hepatologists and the original version has been revised (2). It was not intended for use in individuals with other autoimmune liver diseases; rather it was meant to facilitate making a diagnosis of AIH when the latter was in doubt. Points in favor of the diagnosis are female gender, hepatitic enzymes, elevation in IgG, and detectable nonorgan-specific antibodies, namely ANA or SMA (type 1 AIH) or LKM 1 antibodies (type 2 AIH). If the patient or family members have a history of other autoimmune diseases, this too is given a positive score. The diagnosis of AIH cannot be made without confirmation with liver histology. Specific features on liver histology include interface hepatitis, lymphoplasmacytic infiltrates, rosetting of liver cells, and the absence of biliary changes, Mallory's hyaline, and steatosis. The presence of bridging necrosis and/or fibrosis bodes for a poor outcome without treatment. Points against a diagnosis of AIH are male gender, cholestatic enzymes, recent medications, and alcohol consumption >60 g/day. In addition, AMA positivity and viral hepatitis markers are given a negative score but neither totally exclude the diagnosis of AIH. Although not part of the scoring system, it is important to exclude Wilson disease, which may present just like AIH. CRITERIA FOR TREATMENT OF AIH The three classic randomized controlled trials that evaluated immunosuppressive therapy in the treatment of AIH were conducted in the 1960s (3–5). The criteria for entry into these trials were that patients had symptomatic disease and either an AST >10-fold elevated or an AST >fivefold elevated with a >twofold elevation in IgG. Subsequent analysis of the data indicated that if bridging necrosis and/or multiacinar necrosis was seen on liver biopsy, the height of the aminotransferase and/or IgG was irrelevant (6)! In 2004, patients given a diagnosis of AIH may not fulfill these criteria. Hence, the results of these three trials of immunosuppressive therapy are not necessarily pertinent to all those given a diagnosis of AIH in 2006. These three studies all showed a marked improvement in survival in patients randomized to either prednisone or prednisone in combination with azathioprine. Azathioprine monotherapy was almost as ineffective as placebo. Treatment failure in the 1960s was synonymous with death as there was no liver transplantation available. In the placebo group this occurred in 60% at 3 yr, versus 10% in those randomized to prednisone monotherapy or in combination with azathioprine. It is appropriate in young individuals to start with high-dose prednisone monotherapy, 30–40 mg daily, and decrease the dose once serum aminotransferase levels are 7.5 mg/d (11). In those with underlying cirrhosis it is wise to recommend the wearing of a medic alert bracelet to indicate this diagnosis. The patient needs to understand the importance of regular blood checks, particularly, checking for bone marrow suppression if on azathioprine as well as serial liver biochemical tests and immunoglobulin levels to monitor the dose of immunosuppressive therapy are required. WHEN TO STOP THERAPY Remission is defined as an asymptomatic patient with serum aminotransferase levels that are normal or

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