Development of a Autoimmune Hepatitis Patient's Database Linked to a Biological Sample Storage

Recruiting

• Conditions: Liver Disorder; Autoimmune Hepatitis

• Registration Number: NCT06078098
• Lead Sponsor: University of Milano Bicocca

Brief Summary

Autoimmune Hepatitis (AIH) is chronic fibroinflammatory disease of the liver characterized by chronic, relapsing liver inflammation, and a risk for progression to liver failure and need for liver transplantation. No AIH-specific registry does exist in Italy, so that the actual epidemiology of the disease in the country is unknown.

This is an observational, retrospective and prospective, multicenter study evaluating incidence, prevalence and disease course of AIH in subjects \> 1 years old in Italy.

Detailed Description

Autoimmune Hepatitis (AIH) is a chronic fibroinflammatory disease of the liver characterized by chronic, relapsing inflammation, and a risk for progression to liver failure and development of hepatocellular cancer. Both children and adults are affected. A significant fraction of patients with AIH has a diminished life expectancy, despite treatment. Around 80% of patients respond to current therapies, but their quality of life and health is hugely impaired by side effects. The remaining proportion of patients (the difficult-to-treat category) do not respond to treatment and progress to liver cirrhosis and its complications; thus, timely identification of these individuals is a key aspect of epidemiological research in AIH.Taken together and combined with patients' debilitating quality of life issues, these data highlight the considerable disease burden and clinical impact of AIH on patients' outcomes.

Most epidemiological studies on AIH are retrospective case series based on tertiary referral series with relevant selection biases. Population-based studies, that include all cases in a defined geographical area, provide more accurate estimates of incidence, survival and mortality rate for the individual with AIH. Typically, multiple case-finding approaches have been used, including surveys, laboratory reports, liver histology databases, transplant registries, and death certificates. Only few population-based studies have been performed and limit the research population to a few dozen patients, reporting incidence rates ranging from 1.07 to 1.9 per 100,000 inhabitants. Reported point prevalence is 16.9 per 100,000.

To the investigators knowledge, there have been no epidemiologic studies in AIH carried out in Italy.

The investigators aim to develop a national registry on this rare disease to describe incidence and prevalence of AIH in Italy; identify and define distinct phenotypes and sub-phenotypes of AIH patients; identify factors influencing the progression of AIH and affecting mortality; assess safety and long-term efficacy of novel therapies.

This is a multicentre, nationwide, observational and prospective study based on the development of a patient's database linked to a biological sample storage. The enrollment period will cover 120 months to include the required number of patients. Based on litteraure, the estimated prevalence of AIH in Italy ranges from 6,000 to 15,000. Based on this, the investigators estimate to enroll approximately 10,000 patients. The minimum follow-up time will be 1 year.

Study Timeline

• Study Start: 2023-03-29
• Study First Submitted: 2023-03-31
• Status Verified: 2023-10
• Study First Submitted QC: 2023-10-05
• Last Update Submitted: 2023-10-05
• Study First Posted: 2023-10-11
• Last Update Posted: 2023-10-11
• Primary Completion: 2034-03-29
• Study Completion: 2034-03-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10000

Inclusion Criteria

• All AIH patients living in Italy and aged at least 1 year can be included in the database.
• Willing and able to give informed consent prior to any study specific procedure being
• Diagnosis of AIH according to the most recent published guidelines (EASL)

Exclusion Criteria

• Subject unwilling to participate at the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of participants with Normalization of AST and ALT <1 x upper limit of normal (ULN)) and normal IgG levels within 6 months	Overall duration of the study (11 years)	Number of participants with Normalization of AST and ALT \<1 x upper limit of normal (ULN)) and normal IgG levels within 6 monthswithin 6 months
Number of participants with Hepatitis Activity Index <4/18	Overall duration of the study (11 years)	Number of participants with Hepatitis Activity Index \<4/18
Deep biochemical remissionof disease progression	Overall duration of the study (11 years)	ALT less than 50% ULN and IgG\<12g/l
Number of participants with variceal bleeding requiring hospital admission	Overall duration of the study (11 years)	Number of participants with variceal bleeding requiring hospital admission
Number of participants with platelet count < 150.000/mm3 on more than one consecutive sample	Overall duration of the study (11 years)	Number of participants with platelet count \< 150.000/mm3 on more than one consecutive sample
Number of participants with albumin levels < 3.5 mg/dL on more than one consecutive sample	Overall duration of the study (11 years)	Number of participants with albumin levels \< 3.5 mg/dL on more than one consecutive sample
Number of participants with lack of biochemical response	Overall duration of the study (11 years)	Number of participants with lack of biochemical response
Intolerance to treatment	Overall duration of the study (11 years)	Any adverse event possibly related to treatment as assessed by the treating physician leading to potential discontinuation of the drug
Number of participants with An increase in serum ALT levels above ULN on at least two occasions with an interval of 4 weeks	Overall duration of the study (11 years)	Number of participants with An increase in serum ALT levels above ULN on at least two occasions with an interval of 4 weeks, with or without concomitant clinical symptoms and reinstitution of drug therapy after exclusion of other plausible causes for the elevated serum ALT
Number of participants with <50% decrease of AST and ALT within 4 weeks after initiation of treatment	Overall duration of the study (11 years)	Number of participants with \<50% decrease of AST and ALT within 4 weeks after initiation of treatment
Relapse	Overall duration of the study (11 years)	An increase in serum ALT levels above three times the ULN and/or an increase in serum IgG levels to more than 20 g/l
Number of participants with first evidence of ascites requiring hospital admission	Overall duration of the study (11 years)	Number of participants with first evidence of ascites requiring hospital admission
Number of participants with hepatic encephalopathy requiring hospital admission	Overall duration of the study (11 years)	Number of participants with hepatic encephalopathy requiring hospital admission
Number of participants with serum bilirubin levels > 1.0 mg/dl on more than one consecutive sample	Overall duration of the study (11 years)	Number of participants with serum bilirubin levels \> 1.0 mg/dl on more than one consecutive sample

Secondary Outcome Measures

Name	Time	Method
Number of participants achieving HAI score < 4 at follow-up biopsies	Overall duration of the study (11 years)	Number of participants achieving HAI score \< 4 at follow-up biopsies
Liver stiffness	Overall duration of the study (11 years)	Liver stiffness by fibroscan
The time from the diagnosis of AIH to an event	Overall duration of the study (11 years)	Date of diagnosis of AIH: Defined as the date of the diagnostic liver biopsy, or the date of the first abnormal AST or ALT, or the date of starting therapy in those cases that did not perform a liver biopsy at baseline but fulfilled diagnostic criteria for the disease. Events: Defined as follows: (1) death from a liver-related cause, meaning liver failure, variceal hemorrhage, or HCC; (2) Liver Transplantation for AIH

Trial Locations

Locations (1)

Fondazione IRCCS San Gerardo dei Tintori; 🇮🇹 Monza, MB, Italy