Aminotransferases during treatment predict long-term survival in patients with autoimmune hepatitis type 1: a landmark analysis.

Biochemical remission, important treatment goal in autoimmune hepatitis (AIH), has been associated with better long-term survival. The aim of this study was to determine the independent prognostic value of aminotransferases and immunoglobulin G (IgG) during treatment on long-term transplant-free survival in AIH.In a multicenter cohort ALT, AST and IgG were collected at diagnosis, 6, 12, 24 and 36 months after start of therapy and related to long-term outcome using Kaplan-Meier survival and Cox regression analysis with landmark analysis at these time points, excluding patients with follow-up ending before each landmark.301 AIH patients with a median follow-up of 99 months (range: 7-438 months) were included. During follow-up 15 patients required liver transplantation and 33 patients died. Higher AST at 12 months was associated with worse survival (HR 1.86; p<0.001) while IgG was not associated with survival (HR 1.30; p=0.53). In multivariate analysis AST at 12 months (HR 2.13; p<0.001) was predictive for survival independent of age, AST at diagnosis and cirrhosis. Multivariate analysis for AST yielded similar results at 6 months (HR 2.61; p=0.001), 24 months (HR 2.93; p=0.003) and 36 months (HR 3.03; p=0.010). There was a trend towards a worse survival in patients with mildly elevated aminotransferases (1-1.5 x ULN) compared to patients with normal aminotransferases (p=0.097).Low aminotransferases during treatment are associated with a better long-term survival in autoimmune hepatitis. IgG was not associated with survival in first 12 months of treatment. Normalization of aminotransferases should be the treatment goal for autoimmune hepatitis to improve long-term survival.

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Authors: Maaike Biewenga, Xavier Verhelst, Martine Baven-Pronk, Hein Putter, Aad van den Berg, Isabelle Colle, Jeoffrey Schouten, Filip Sermon, Christophe Van Steenkiste, Hans van Vlierberghe, Adriaan van der Meer, Bart van Hoek, Dutch Autoimmune Hepatitis Study Group