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The response to immunosuppressive therapy in autoimmune hepatitis (AIH) is a matter of debate. The aim of this work is to identify the histological, biochemical, and clinical predictive factors of incomplete response/treatment failure to the standard treatment (prednisone with or without azathioprine) in a well-characterized series of AIH Egyptian patients.Of 49 AIH patients, only 36 patients completed this retrospective cohort study. The immunological, biochemical, histopathological, and clinical characteristics of patients were evaluated at diagnosis and during follow-up.Patients were classified into two groups; group A showed a complete response to therapy (n=22; 61%) and group B showed partial response/treatment failure (n=14; 39%). In a multivariate analysis, we observed that age at diagnosis up to 22 years [odds ratio (OR): 23.22; confidence interval (CI): 3.978–135.549; P<0.001], serum albumin up to 3.2 g/dl (OR: 5.36; CI: 1.237–23.209; P=0.025), mean platelet volume (MPV) of at least 10.75 fl (OR: 16.5; CI: 3.093–88.037; P<0.001), and presence of cirrhosis at diagnosis (OR: 8.44; CI: 1.682–42.392; P=0.001) were independent variables that can predict partial response/treatment failure. MPV correlated positively with stages of fibrosis/cirrhosis and grades of activity in liver biopsy at diagnosis and correlated inversely with serum albumin and age at presentation. During therapy, group B showed a fluctuation in MPV levels, however, group A showed a progressive decline until the end point.Our study confirmed that younger age, hypoalbuminemia, increased MPV, and cirrhosis at diagnosis were all independent predictors of incomplete response/treatment failure in AIH patients. MPV may reflect the response to therapy.