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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Multicenter, Nationwide, Observational, Retrospective and Prospective Study Based on the Development of a Autoimmune Hepatitis Patient's Database Linked to a Biological Sample Storage

Conditions
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Autoimmune Hepatitis, Liver Disorder

Intervention / Treatment
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* Other: Clinical Information


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AIH patients<br>AIH population in Italy aged at least 1 year | Other: Clinical Information<br>* We will recruit AIH patients and collect important clinical information and laboratory investigation, together with biological samples.<br>* Other names: Biological samples;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Normalization of AST and ALT <1 x upper limit of normal (ULN)) and normal IgG levels within 6 months | 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 | Overall duration of the study (11 years) | 
| Number of participants with lack of biochemical response | Number of participants with lack of biochemical response | Overall duration of the study (11 years) | 
| Number of participants with <50% decrease of AST and ALT within 4 weeks after initiation of treatment | 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 Hepatitis Activity Index <4/18 | Number of participants with Hepatitis Activity Index <4/18 | Overall duration of the study (11 years) | 
| Intolerance to treatment | Any adverse event possibly related to treatment as assessed by the treating physician leading to potential discontinuation of the drug | Overall duration of the study (11 years) | 
| Deep biochemical remissionof disease progression | ALT less than 50% ULN and IgG<12g/l | Overall duration of the study (11 years) | 
| Relapse | 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 | 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 | 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 | Overall duration of the study (11 years) | 
| Number of participants with variceal bleeding requiring hospital admission | Number of participants with variceal bleeding 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 first evidence of ascites requiring hospital admission | Overall duration of the study (11 years) | 
| Number of participants with hepatic encephalopathy requiring hospital admission | Number of participants with hepatic encephalopathy requiring hospital admission | Overall duration of the study (11 years) | 
| Number of participants with serum bilirubin levels > 1.0 mg/dl on more than one consecutive sample | 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 platelet count < 150.000/mm3 on more than one consecutive sample | 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 albumin levels < 3.5 mg/dL 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver stiffness | Liver stiffness by fibroscan | Overall duration of the study (11 years) | 
| Number of participants achieving HAI score < 4 at follow-up biopsies | Number of participants achieving HAI score < 4 at follow-up biopsies | Overall duration of the study (11 years) | 
| The time from the diagnosis of AIH to an event | 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 | Overall duration of the study (11 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune Hepatitis, National Database, Liver, Epidemiology