1. Budesonide induces remission more effectively than Prednisone in a controlled trial of patients with Autoimmune Hepatitis GASTROENTEROLOGY 2010;139:1198–1206 R2 소예리

2. Background Autoimmune hepatitis (AIH): - a chronic liver disease ass. with cirrhosis and liver failure. - significant potential for morbidity and mortality. Characterized as - a disease with hyper-gammaglobulinemia (mainly IgG) - associated with extrahepatic autoimmune syndromes and high necro-inflammatory activity, - frequently accompanied by histologic signs of chronic hepatitis. Current management of AIH: Prednisone alone or in combination with azathioprine → remission in approximately 80%

3. Corticosteroid therapy : long-term remission but has many side effects. (such as jaundice, leucopenia, and anemia) Budesonide : has 90% first-pass effect in the liver improve liver function in patients with AIH. We compared the effects of Budesonide (a steroid that is rapidly metabolized, with low systemic exposure) and Prednisone, both in combination with azathioprine.

4. Materials and Methods - 10–70 years of age - either a first diagnosis of acute AIH based on liver biopsy results obtained < 3 months before screening or were experiencing relapse after a previous diagnosis of AIH based on histology findings <12 months before screening, according to the criteria of the International Autoimmune Hepatitis Group - Thiopurine methyltransferase activity and ACTH levels in the normal range - Serum ALT or AST levels 2 times higher than the upper limit of normal - normal levels of 1-antitrypsin, serum copper, and ceruloplasmin - elevated levels of r-globulins or IgG. - the presence of hepatitis A, B, C, D, or E virus infection - primary biliary cirrhosis - primary sclerosing cholangitis - Wilson disease, hemochromatosis - liver cirrhosis - fulminant liver failure - recent treatment with drugs having known liver toxicity - parenteral administration of blood or blood products within 6 months before screening. Inclusion criteriaExclusion criteria

6. Primary efficacy end point: complete response to therapy, defined as complete biochemical remission (ie, serum AST and ALT within normal range) at the patient’s last visit of segment A, and the absence of predefined steroid-specific side effects throughout segment A. Secondary end points: complete biochemical remission and the occurrence or absence of steroid-specific side effects.

7. Results

8. Study Population

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11. Efficacy

13. Safety and Tolerability >>

14. Discussion First study to directly compare budesonide to prednisone. Used a stringent definition for response: complete normalization of biochemistry in the absence of steroid-specific side effects. - 1 st, well-tolerated induction of complete biochemical remission is likely to reduce long-term hepatic damage. - 2 nd, residual aminotransferase activity almost universally leads to relapse after drug withdrawal. The sensitivity of this definition is shown by the fact that more relaxed definition of remission showed little difference between groups.

15. We considered whether baseline differences between study groups (Gender, Body weight, HLA types) could have influenced the observed results. → variations in baseline characteristics are not believed to have confounded the observed difference in response rates. Treatment response according to autoantibody profile (ANA, LKM-1 Ab, SLA/LP Ab) was analyzed, ; no significant differences between serologic subtypes. → The improved complete response rate seen with budesonide versus prednisone was maintained for all 3 serologic subtypes of AIH (data not shown).

16. Conclusion Oral budesonide, in combination with azathioprine, induces and maintains remission in patients with noncirrhotic AIH, with a low rate of steroid-specific side effects.