Factors Predicting Relapse and Poor Outcome in Type I Autoimmune Hepatitis: Role of Cirrhosis Development, Patterns of Transaminases During Remission and Plasma Cell Activity in the Liver Biopsy

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Abstract
To determine factors predicting relapse and poor outcome in patients with type I autoimmune hepatitis (AIH). Patients with AIH were retrospectively recruited. Definitions—remission: AST/ALT < 2 ULN; relapse: AST/ALT ≥ 2 ULN; poor outcome: cirrhosis complications, transplantation (OLTx), and death; abnormal transaminases: AST/ALT > ULN but within the remission range; abnormal transaminases index (ATI): number of occasions AST/ALT abnormal/years of remission. Liver biopsies were assessed by Ishak system, and additional score given for portal and parenchymal plasma cells. Data are presented as median (range). Seventy-one patients were identified. Twenty (28%) had cirrhosis at presentation, 14 (20%) developed it during follow-up of 52 months (18–336). Of the 14, four had histological confirmation, and the remainder had clinical/radiological evidence of cirrhosis. Factors independently associated with cirrhosis development were inability to have consistently normal transaminases during remission, OR 19.3 (95% CI 2.2–40), p= 0.002. Treatment was discontinued in 40/69 patients of whom 30 (75%) relapsed within 2 months (1–23), culminating in one death. Factors independently associated with relapse were: time to initial remission, OR 5.5, 95% CI 1.3–22, p= 0.01; failure to have consistently normal transaminases during remission OR 11.8, 95% CI 1.3–100, p= 0.02; and portal plasma cell score (PPCS) OR 10.6 (95% CI 1.0–107), p= 0.04. Time to remission ≥ 5 months, PPCS ≥ 3 and ATI ≥ 2 was associated with >90% probability of relapse (PPV 100%). Fifteen percent had a poor outcome. Independent predictors of poor outcome were: globulins at onset OR 3.4 (95% CI 1.1–10.1), p= 0.02 and cirrhosis development, OR 23 (95% CI 1.7–307), p= 0. Seventy percent of patients with AIH relapse upon drug cessation. Time to remission ≥ 5 months, ATI ≥ 2 and PPCS ≥ 3 were associated with >90% probability of relapse. Factors predicting poor outcome were globulins at onset and cirrhosis development.