A Study to Assess the Genetic Variations in Bile Flow Disorders: Linking Progressive Familial Intrahepatic Cholestasis (PFIC)-Related Genes to Symptoms in Adults With Recurrent Cholestasis in Spain

Defined as the percentage of participants with at least one variant in PFIC-related genes in relation to the total number of participants with idiopathic recurrent and/or chronic cholestasis of the study cohort as an assessment of prevalence.

Defined as the percentage of participants carrying each identified variant of genes related to PFIC.

Defined as the mean age of participants recorded at the time of enrollment, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the count of sex of participants recorded at the time of enrollment, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the race/ethnicity of participants recorded at the time of enrollment, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the mean weight participants recorded at the time of enrollment, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the mean height participants recorded at the time of enrollment, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the mean BMI, calculated by dividing participant's weight in kilograms by the square of their height in meters (BMI = weight ÷ height²), as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the mean of standard drinks in a week to assess the alcohol consumption, recorded at the time of enrollment, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the mean participant's age when first symptoms were reported, as noted in medical records or participant recollection, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the count of presence of liver conditions such as gallstones, pancreatitis, and cirrhosis (among other relevant conditions), as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the count of presence of diagnostic procedures performed, including liver biopsy and elastography (Fibroscan) as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the count of presence of liver condition symptoms such as jaundice, pruritus and disease-related fatigue, as noted in medical records or participant recollection, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the count of history of liver or biliary disease related surgeries, such as cholecystectomy, liver transplantation, surgical biliary diversion (SBD) or other liver-related surgery, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the count of family history of liver disease, such as the presence or absence of PFIC, intrahepatic cholestasis of pregnancy (ICP), benign recurrent intrahepatic cholestasis (BRIC), low-phospholipid-associated cholelithiasis (LPAC), portal hypertension, hepatocellular carcinoma, cholangiocarcinoma, pancreatitis, gallstones, cirrhosis, cholestatic drug induced liver injury (DILI), Metabolic dysfunction-associated fatty liver disease (MASLD), Non-alcoholic Steatohepatitis (MASH) and any other chronic liver disease, and which close relative has suffered it (parent, grandparent, sibling, etc.), as noted in medical records or participant recollection, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the count of presence or absence of vitamin deficiencies, such as vitamin A, D, E and K and supplementation, as noted in medical records or participant recollection, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the last recorded routine analysis of haemoglobin, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the last recorded routine analysis of RBC count, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the last recorded routine analysis of leukocytes, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the last recorded routine analysis of platelets, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the recorded routine analysis of ALT, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the recorded routine analysis of AST, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the recorded routine analysis of ALP, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the recorded routine analysis of total and direct bilirubin, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the recorded routine analysis of sBA, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the recorded routine analysis of GGT, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the recorded routine analysis of albumin, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the recorded routine analysis of prothrombin time, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the recorded routine analysis of INR, as noted in medical records, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the count of prior and concomitant treatment for cholestatic liver disease and pruritus: ursodeoxycholic acid (UDCA), cholestyramine, rifampicin, fibrates, ileal bile acid transporter inhibitors (IBATi), selective serotonin reuptake inhibitors (SSRI), opioid antagonists, Chaperones (4- phenylbutyrate, [4-PB]) skin emollients or others, as noted in medical records or participant recollection, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.

Defined as the count of comorbidities of interest, such as diabetes, metabolic syndrome, osteopenia/osteoporosis, as noted in medical records or participant recollection, stratified by the PFIC type - comparing those with the most prevalent PFIC variant against all other participants.