Original article
Pancreas, biliary tract, and liver
Rapid Response to Treatment of Autoimmune Hepatitis Associated With Remission at 6 and 12 Months

https://doi.org/10.1016/j.cgh.2019.11.013Get rights and content

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 response 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.

Section snippets

Study Design

We performed a retrospective cohort study, establishing 2 independent cohorts of patients with AIH from 12 centers across 7 countries in Europe. We included patients with a probable or definite AIH diagnosis according to the simplified International Autoimmune Hepatitis Group score.7, 8, 9 When patients scored as “no AIH” by the simplified criteria, but were treated by their physicians as patients with AIH, the revised score was used to calculate a score per patient. Only patients with a

Population

Both the discovery and validation cohort consisted of 370 patients. Most patients were female (74.5%). Patients in the validation cohort were slightly older at time of diagnosis compared with patients in the discovery cohort (49.58 years vs 47.09 years; P = .04). Other baseline and treatment characteristics were comparable between the cohorts (Supplementary Table 1).

Receiver Operating Characteristic Analysis

Percentage decrease of AST after 8 weeks of treatment was significantly associated with normalization of transaminases at 26 weeks

Discussion

We show that patients with AIH with a substantial decrease (≥80%) of transaminases in the first 8 weeks of treatment have a high chance of normalization of transaminases and biochemical remission after 26 and 52 weeks of treatment. A rapid treatment response was independently associated with a lower risk of liver-related death or liver transplantation, although only in the discovery cohort. The clinical consequence of these observations is that ≥80% decrease in transaminase levels within 8

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Conflicts of interest The authors disclose no conflicts.

Funding Maria Papp was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00232/17/5) and the New National Excellence Program of the Ministry of Human Capacities (ÚNKP-19-4 Bolyai Plus).

a

Member of the European Reference Network RARE-LIVER.

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