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Biomarkers to Predict the Success of Immunosuppression Withdrawal in Autoimmune Hepatitis

NCT03711669 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 96

Last updated 2020-02-12

No results posted yet for this study

Summary

Autoimmune hepatitis (AIH) is an inflammatory, chronic and recurrent liver disease of unknown etiology that can lead to cirrhosis or acute liver failure. It is a rare disease affecting 16 cases every 100,000 persons in Europe, mainly in women in every age group. It is characteristic the presence of high levels of aminotransferases, hypergammaglobulinemia and high titres of autoantibodies, as well as interface hepatitis in the biopsy.

Due to the autoimmune etiology of AIH, treatment is based on immunosuppressive strategies, mainly prednisone and azathioprine regimens which make possible to achieve remission in approximately 75% of cases with moderate or severe hepatocellular inflammation.

Remission is defined as a normalization in aminotransferases, immunoglobulin G (IgG) and resolution histological inflammation (this last one comes after biochemical remission). It has also been observed that there is a restoration in number and function of Tregs after achieving remission.

The rates of recurrence after withdrawing it varies from 30-87% depending on the studies and their follow-up. It is usual to maintain treatment indefinitely in clinical practice. This strategy implies maintaining treatment for long periods of time in patients that could be available to maintain sustained remission, exposing them to adverse effects. From all these, we think it is important to be able to identify patients who will be able to maintain biochemical and histological remission without immunosuppression (IS), which still is not known in this disease's management.

Some observational and retrospective studies have identified some parameters that could imply a higher risk of recurrence after stopping treatment such as high levels of aminotransferases and IgG, less time of remission before withdrawal (specifically less than 2 years) or presence of interface hepatitis in a biopsy prior discontinuation of treatment. However, the accuracy of these parameters is low and as a result, management of this disease has not changed much over the past decades, still having patients under prolonged treatment unnecessarily.

For the previously mentioned reasons, there is a need to identify new biomarkers that allow clinicians selecting patients with AIH in whom treatment could be stopped avoiding its costs and adverse effects. At the same time, it would help to understand the immunopathogenesis of AIH and identification of new therapeutic targets.

Conditions

  • Autoimmune Hepatitis

Interventions

BEHAVIORAL

Immunosuppression withdrawal

IS will be tapered gradually over a period of 6 months. Azathioprine will be stopped during the first 3 months, reducing the dose 50% every month. Prednisone will be tapered 2.5mg monthly until total withdrawal. During withdrawal and the first year after stopping treatment patients will undergo laboratory tests on a monthly basis, afterwards follow-up will be done every 3 months until the end of the project.

Sponsors & Collaborators

  • Hospital Clinic of Barcelona

    lead OTHER

Principal Investigators

  • Maria C Londoño, MD, PhD · Hospital Clinic of Barcelona

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-01-10
Primary Completion
2021-01-31
Completion
2021-04-30

Countries

  • Spain

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03711669 on ClinicalTrials.gov