Autoimmune hepatitis may fail to respond to corticosteroid therapy, but the frequency and bases for this outcome are uncertain. We aimed to determine the frequency and nature of treatment failure in patients with type 1 autoimmune hepatitis, define features associated with its occurrence, and assess if the model for end-stage liver disease can predict this outcome. Patients failing conventional corticosteroid regimens were compared to patients who responded to similar regimens. Fourteen of 214 patients (7%) failed corticosteroid treatment. Patients who failed therapy were younger (33 ุ 3 years versus 48 ุ 1 years, P โซุโฌ 0.0008), had higher serum levels of bilirubin at accession (4.1 ุ 0.9 mg/dL versus 2.3 ุ 0.2 mg/dL, P โซุโฌ 0.02), presented acutely more frequently (43% versus 14%, P โซุโฌ 0.01), and had a higher frequency of HLA (human leukocyte antigen) DRB1*03 (93% versus 53%, P โซุโฌ 0.004) than did patients who achieved remission. An alternative disease (fatty liver disease) emerged in only 1 patient who failed therapy (7%). Scores determined by the model of end-stage liver disease at presentation of patients who failed treatment were higher than those of who achieved remission ( 16ุ 1 versus 10 ุ 0.3 points, P < 0.0001), and score greater than 12 points had greater sensitivity (97%) and specificity (68%) for treatment failure than did HLA DRB1*03 or other features. Conclusion: Onset at an early age, acute presentation, hyperbilirubinemia, and presence of HLA DRB1*03 characterize patients who fail corticosteroid treatment. The model for end-stage liver disease may be a useful instrument for identifying patients prone to this outcome. (HEPATOLOGY 2007;46:1138-1145.)
C orticosteroids are effective in the treatment of most patients with autoimmune hepatitis, but deterioration is still possible despite compliance with therapy. 1,2 High doses of prednisone alone or in combination with azathioprine can improve the clinical and laboratory manifestations of treatment failure, but histological resolution is uncommon. 2,3 These patients typically require indefinite therapy, and they remain at risk for drug toxicity and liver failure. The results of empiric treatment with ursodeoxycholic acid, 4 cyclosporine, 5,6 tacrolimus, 7,8 mycophenolate mofetil, 9-12 cyclophosphamide, 13 methotrexate, 14 rituximab, 15 budesonide, 16 intravenous globulin, 17 or leukocytopheresis 18 attest to the refractory nature of this condition.
The frequency of treatment failure and the basis for deterioration during corticosteroid therapy are unknown. Corticosteroid responsiveness is a defining feature of autoimmune hepatitis, and failure of the disease to improve suggests an alternative diagnosis. 19 Many diseases can resemble autoimmune hepatitis, including Wilson disease, chronic hepatitis C, fatty liver disease, primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). These conditions may be unrecognized at presentation and account for treatment failure.
Autoimmune hepatitis may also undergo transitions during its course, with a cholestatic syndrome emerging that might be refractory to the original treatment. 20 Furthermore, another condition may be superimposed on the original process, such as PSC, [21][22][23][24] viral infection, 25 drug toxicity, 26 or fatty liver disease, 27 which could alter treatment outcome. Last, treatment failure may reflect intrinsic pathogenic mechanisms promoted by host-dependent