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Clin Gastroenterol Hepatol. 2019 Nov 9. pii: S1542-3565(19)31268-6. doi: 10.1016/j.cgh.2019.11.013. [Epub ahead of print]

Rapid Response to Treatment of Autoimmune Hepatitis Associated with Remission at 6 and 12 Months.

Author information

1
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands; European Reference Network RARE-LIVER.
2
Department of Gastroenterology and Hepatology, Rijnstate hospital, Arnhem, The Netherlands.
3
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
4
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
5
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; European Reference Network RARE-LIVER.
6
Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
7
Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland.
8
Department of Gastroenterology, Harran University Hospital, Urfa, Turkey.
9
Department of Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey.
10
Department of Gastroenterology, Hacettepe University, Ankara, Turkey.
11
Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Leuven. Belgium.
12
Department of Gastroenterology and Hepatology, University Clinic of Essen Duisburg-Essen, Germany.
13
1(st) Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; European Reference Network RARE-LIVER.
14
1(st) Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network RARE-LIVER.
15
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands; European Reference Network RARE-LIVER. Electronic address: joostphdrenth@cs.com.
16
Institute of Liver Studies, King's College Hospital, London, United Kingdom; European Reference Network RARE-LIVER.

Abstract

BACKGROUND & AIMS:

Changes in serum levels of transaminases immediately after initiation of treatment for autoimmune hepatitis (AIH) might be associated with biochemical markers of remission and liver-related events. We assessed the outcomes of patients with vs without rapid responses to treatment of AIH in a large international cohort.

METHODS:

We performed a retrospective cohort study, collecting data from 2 independent cohorts of adults with AIH from 12 centers in 7 countries in Europe. We collected information on patient demographics; serologic, histologic, and biochemical analyses; and treatment. We used a receiver operating characteristic curve and Youden index to calculate the optimal percentage decrease in level of aspartate aminotransferase (AST) after 8 weeks of treatment that associated with normalization of transaminase levels after 26 weeks of treatment with predniso(lo)ne (primary outcome) in the first (discovery) cohort (n = 370). We evaluated the results in the second (validation) cohort (n = 370). Secondary outcomes were liver-related death or transplantation. We performed univariate and multivariable logistic and Cox regression with correction for confounders.

RESULTS:

A significant decrease in level of AST after 8 weeks of treatment was significantly associated with normalization of transaminase levels at 26 and 52 weeks (P<.001); a decrease of more than 80% in level of AST was associated with optimal normalization. In both cohorts, rapid responders (≥80% decrease in level of AST after 8 weeks) were more likely to achieve normalization of transaminases at 26 and 52 weeks when compared to non-rapid responders. Rapid responders in the discovery cohort had lower risk of liver-related death or transplantation (adjusted hazard ratio 0.18; 95% CI 0.05-0.63; P=.007), although this was not confirmed in the validation cohort. Results from measurement of alanine aminotransferase did not differ significantly from those of AST for the primary outcome. Slow responders (without normalization of transaminases after 1 year) had the highest risk of liver transplantation or liver-related death.

CONCLUSIONS:

In a retrospective study of patients with AIH, we found that a rapid response to treatment, based on level of AST after 8 weeks, associates with normalization of transaminase levels in the following year. Patients with a rapid response also have a lower risk of liver-related death or transplantation than patients without this rapid response.

KEYWORDS:

Induction therapy; liver enzyme; prognostic factor; steroid

PMID:
31715274
DOI:
10.1016/j.cgh.2019.11.013

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