National Database on Primary Biliary Cholangitis

Study Overview
=================
Brief Summary
-----------------
Primary biliary cholangitis (PBC) is a rare, autoimmune, cholestatic liver disease. No data about the disease epidemiology exist in Italy. Therefore this study aims to develop a national PBC patient database linked to a biological sample storage.

Detailed Description
-----------------
Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by chronic inflammation of the intrahepatic bile ducts, causing progressive ductopenia, cholestasis, and if not effectively treated, leading to fibrosis, cirrhosis and liver failure. Nowadays almost all patients with PBC are diagnosed at an early disease stage and receive treatment with ursodeoxycholic acid (UDCA) which is currently the only drug approved for the treatment of patients with PBC. However, approximately 20% to 30% (up to >50% in patients presenting under the age of 40 years) still does not have a benefit from UDCA and has a reduced prognosis as compared to healthy individuals. Major steps forwards in the field of PBC have been done in the last decade, however there are still significant areas of unmet clinical need in PBC: the lack of knowledge on etiopathogenesis; a poor understanding of disease sub-phenotypes; the lack of biomarkers of disease progression that allow risk stratification needed in clinical management and trials design, among the others. In the current evolving research landscape with the availability of the -omics technologies generating libraries of genome-wide data, metabolomics and proteomics data, among the others, the prospects of discovering the gene and molecular underpinnings of PBC are more promising than ever. Scientists envision an era of personalized medicine when more and more people will obtain their own genetic and metabolic maps, enabling them to identify their status as carriers of specific risk profiles. Based on these premises, the current project aims to build up a research, nation-wide infrastructure (around 60 Italian participating centres will be involved) to study the biology of PBC and, in particular, to explore why a significant group of, typically young patients fail primary therapy with UDCA, placing them at risk of developing progressive disease and needing liver transplantation (LT). The investigators will recruit patients and organise the collection of important clinical information and laboratory investigation, together with biological samples. Data will be collected in the form of electronic Case Report Forms (REDCap cloud) that will be completed by clinicians at baseline and thereafter on an annual basis. The clinical information will allow us to identify patients' clinical profiles. The biological samples will allow to understand key aspects of people's make up, including patient genes and the way their immune system works, and the differences in make up between people with different clinical phenotypes. This research infrastructure would represent an invaluable resource for successful translational research in this field. Specifically, it would serve investigators conducting research; clinicians treating patients; epidemiologists gathering demographic data; and the drug and device industry seeking new markets. It also can represent a necessary infrastructure for the implementation of the European Reference Networks (ERN) for rare diseases, main pillars of the current EU policy framework on National Plans for research and development. The Italian PBC database would also be crucial for drug development, specifically to assess the feasibility of clinical trials, to facilitate the planning of appropriate clinical trials, to support the enrolment of patients and to assess the impact of new interventions.

Official Title
-----------------
Multicenter, Nationwide, Observational, Retrospective and Prospective Study Based on the Development of a Patients Database Linked to a Biological Sample Storage

Conditions
-----------------
Primary Biliary Cholangitis

Intervention / Treatment
-----------------
* Other: Clinical information


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All PBC patients living in Italy and aged at least 18 years can be included in the database. According to well-established criteria, PBC is diagnosed in subjects who fulfill two of the three of following criteria: elevated alkaline phosphatase and /or GGT; positive anti-mitochondrial autoantibodies (titer ≥ 1:40) or PBC-specific antinuclear antibodies (gp-210 and sp100); characteristic histological features of florid bile ducts lesions and granulomatous lesion. Exclusion Criteria: The patient has explicitly declared his/her unwillingness to participate to the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PBC population residing in Italy<br>All PBC patients living in Italy and aged at least 18 years can be included in the database. According to well-established criteria, PBC is diagnosed in subjects who fulfill two of the three of following criteria: elevated alkaline phosphatase and /or GGT; positive anti-mitochondrial autoantibodies (titer ≥ 1:40) or PBC-specific antinuclear antibodies (gp-210 and sp100); characteristic histological features of florid bile ducts lesions and granulomatous lesion. | Other: Clinical information<br>* The investigators will recruit PBC patients and collect important clinical information and laboratory investigation, together with biological samples.<br>* Other names: Biological samples;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phenotypes and sub-phenotypes of PBC Italian patients | Identify and define distinct phenotypes and sub-phenotypes of PBC patients at higher risk of disease progression. | Overall duration of the study (10 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to UDCA therapy | Defined as Alkaline Phosphatase Level<1 x upper limit of normal. The investigators will fit a multivariate analysis using logistic regression using baseline variables. | Overall duration of the study (10 years) | 
| Identification of factors influencing the progression of PBC | The investigators will calculate the time from the diagnosis of PBC to an event (liver decompensation, liver transplantation or death). They will then fit a multivariate analysis using Cox's proportional hazards regression model of diverse explanatory variables available at baseline. | Overall duration of the study (10 years) | 
| Safety and long-term efficacy of novel therapies | The investigators will evaluate prospectively laboratory investigation and the treatment response to novel therapies that are entering the clinical practice, e.g. obeticholic acid, fibrates. | Overall duration of the study (10 years) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Primary Biliary Cholangitis, Disease phenotypes, National Database