An observational study in De Novo Autoimmune Hepatitis, sponsored by Yale University. Terminated. Open to participants aged 3 Months and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-12-10.
Sponsored by Yale University · Observational
The purpose of this study is to provide insights into the cause, development and effects of de novo autoimmune hepatitis so that prevention and treatment strategies can be developed in order to reduce post-liver transplant morbidity, the frequency of liver allograft loss and the need for re-transplantation.
This is a multi-site study with Yale University as the coordinating site. Our research plan is as follows:
Aim 1: To conduct a refined phenotypical and functional analysis of regulatory T cells in study and control patient groups.
Rationale: We would like to extend our preliminary data observations in a larger patient group and use this extended data set to conduct a refined phenotypical and functional analysis of regulatory T cells in order to explore if the regulatory T cell phenotype and function in d-AIH differs: (A) from that in controls defined as (i) non-transplanted patients with autoimmune hepatitis (AIH), (ii) LT recipients with acute rejection, (iii) LT recipients with chronic rejection, (iv) non-transplanted patients with chronic hepatitis C; (B) according to the disease etiology leading to transplantation; (C) according to immunosuppressive regimen prior to diagnosis of d-AIH being made and (D) over time during the disease course. This could potentially give us some insight into the causes for immune tolerance breakdown in d-AIH.
Aim 2: To investigate how over expression of IL-17A and HDAC9 genes relates to the regulatory T cell defect observed in liver transplant recipients with d-AIH.
Rationale: Histone/protein deacetylases regulate chromatin remodeling, gene expression and the functions of many transcription factors. Acetylation of histones leads to an open chromatin structure permissive for the initiation of gene transcription and expression. Histone deacetylase inhibition by Trichostatin-A (TSA) has been demonstrated to prevent the production of IL-17A and sustain Foxp3 expression in human T-regs. Importantly, if differentiation of T-regs into a Th17-like phenotype can be inhibited by TSA in d-AIH, this might be of interest for the development of new therapeutic modalities.
We would like to first of all confirm our preliminary data observations in a larger patient population and address any concerns about RNA integrity in formalin fixed paraffin embedded tissue by using fresh liver biopsy tissue to assess the expression of genes involved in T-cell anergy and immune tolerance in LT recipients.
2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.
This study's enrollment of 157 is below the median of 250 across 687 observational studies indexed under Hepatitis A.
Browse Hepatitis A studies →Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.
Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Cohorts will be obtained from clinical settings and include pediatric and adult subjects. See eligibility criteria for detailed descriptions of the population.
Pediatric Transplant Patients
Healthy Pediatric Control Subjects (Enrolled at Yale)
Adult Control Subjects (Enrolled at Yale) Non-transplanted Adult patients with autoimmune hepatitis and chronic hepatitis C will also be enrolled.
Exclusion Criteria:
Pediatric Transplant Patients - Multi-visceral organ transplant recipient
Healthy Pediatric Control Subjects (Enrolled at Yale)
Adult transplanted patients with d-AIH (enrolled at Yale)
Pediatric transplant patients with de novo autoimmune hepatitis (d-AIH) will be enrolled at an outside center.
Other: Pediatric transplant subject with d-AIH
Pediatric transplant patients with acute rejection will be enrolled at an outside center.
Other: Pediatric transplant subject with acute rejection
Pediatric transplant patients with chronic rejection will be enrolled at an outside center.
Other: Pediatric transplant subject with chronic rejection
Healthy pediatric patients will be enrolled at the coordinating center (Yale).
Other: Pediatric control subjects
Adult non-transplant patients with auto-immune hepatitis will be enrolled at the coordinating center (Yale).
Other: Adult non-transplant patients with auto-immune hepatitis
Adult non-transplant patients with chronic hepatitis C will be enrolled at the coordinating center (Yale).
Other: Adult non-transplant subjects with chronic hepatitis C virus
Adult transplanted patients with de novo autoimmune hepatitis will be enrolled at the coordinating center (Yale).
Other: Adult transplanted subjects with de novo autoimmune hepatitis
30 ml of blood will be collected during periods of disease quiescence and activity in recipients with d-AIH who are enrolled. The exact number of blood draws will depend on the patient's pattern of disease activity. No more than one blood draw will take place during an 8-week period. The maximum amount of blood draws over the 2 year study period will be 8.
Recipients with acute rejection will have blood drawn at time of diagnosis before treatment for rejection is instituted.
Recipients with chronic rejection will have blood drawn either at diagnosis before treatment is instituted or for those with ongoing chronic rejection at the time of enrollment.
75 ml of blood will be collected during periods of disease quiescence and activity in non transplanted subjects with AIH who are enrolled. Research blood draws will be drawn along with clinical blood draws. The exact number of blood draws for each subject will depend on his or her pattern of disease activity. No more than one blood draw will take place during an 8-week period. The maximum amount of blood draws over the 2 year study period will be 8. Liver tissue (2 mm) will be obtained at the time a clinically indicated liver biopsy is performed. In the event that any enrolled subject undergoes liver transplantation, a portion of the explanted liver will be obtained and stored in special media.
For enrolled patients with chronic hepatitis C, 75 ml of blood will be collected before the start of treatment. This will be a onetime blood draw prior to treatment. Liver tissue (2 mm) will be obtained at the time a clinically indicated liver biopsy is performed. In the event that any enrolled patient undergoes liver transplantation, a portion of the explanted liver will be obtained and stored in special media.
2 tablespoons of blood (30 ml) will be collected at each blood draw over a 2-year period. . The maximum amount of blood draws will be 3 however there will be no more than 1 blood draw within an 8-week period.
75 ml of blood will be collected during periods of disease quiescence and activity in recipients with d-AIH who are enrolled. The exact number of blood draws for each subject will depend on his or her pattern of disease activity. However, no more than one blood draw will take place during an 8-week period. The maximum amount of blood draws over the 2-year study period will be 8.
Liver Allograft Loss
Assessment to determine the frequency of liver allograft loss.
Time frame: 3 years
Need for Transplantation
Assessment to determine the need for re-transplantation.
Time frame: 3 years
No study locations are listed for this record.
This study is terminated, as verified in Dec 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Yale University