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Disease activity and response to treatment in autoimmune hepatitis is assessed best by liver biopsy, which does not suit for regular disease monitoring. It is frequent clinical practice to follow disease by assessment of serologic markers. Here, we assessed the diagnostic fidelity of this clinical practice.One hundred thirty-one biopsies from 82 patients with autoimmune hepatitis were analyzed for histologic activity. Serum samples, taken at the time of biopsy, were analyzed for aminotransferases [alanine aminotransferase (ALT), aspartate aminotransferase], IgG, and γ-globulin levels and compared with histology.All serum parameters were significantly associated with histologic activity (P<0.0075); ALT and IgG were most complementary. Presence of both elevated ALT and IgG were associated with high inflammatory activity (histologic activity scores ≥6) with 99% sensitivity. Elevation of either IgG or ALT was associated with residual inflammatory activity in almost all patients. Histologic remission is reliably indicated by normalization of both serum parameters, but about half of the patients with normal serum parameters still showed residual histologic activity of histologic activity index (HAI) 4 or 5. However, our patients with HAI scores 4 or 5 were at significantly lower risk of fibrosis progression than patients with scores ≥6 (P<0.02; odds ratio 14.2).Histologic activity seems to be reliably indicated by elevated serum parameters. Normalization of serum parameters is not a reliable marker for complete histologic remission (HAI 1 to 3); however, normalized serum parameters identified patients at low risk of fibrosis progression. Thus, the common clinical practice of disease monitoring by serum markers seems to be suitable for regular follow-up.