• ABCB4 gene
• Liver transplantation; machine learning
• Mutation spectrum
• PFIC3

• Humans
• ATP Binding Cassette Transporter, Subfamily B/genetics
• ATP Binding Cassette Transporter, Subfamily B/deficiency
• Cholestasis, Intrahepatic/genetics
• Male
• Female
• Genetic Association Studies
• Mutation, Missense
• Infant
• Mutation
• Phenotype
• Child, Preschool
• Child

• 242300420070 the Natural Science Foundation of Henan Province
• 2022-MEKLLC-ZD-002 the Open Project of Key Laboratory of the Ministry of Education
• 81902904 the National Natural Science Foundation of China

• Bile acids
• PFIC
• bile salt export pump
• enterohepatic circulation
• ileal bile acid transporter

• Humans
• Cholestasis, Intrahepatic/drug therapy
• Drug Development
• Bile Acids and Salts/metabolism
• Animals
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Drug Design

• Cholestatic liver disease
• Liver pathology
• MDR3/ABCB4 gene
• Novel mutation

• Adult
• Child
• Humans
• ATP Binding Cassette Transporter, Subfamily B/deficiency
• China
• Cholestasis/genetics
• Cholestasis, Intrahepatic/genetics
• Liver Cirrhosis
• Retrospective Studies

• 2022-1-2182 Capital Medical Development Fund

• ABCB11
• Cholestatic Jaundice
• PFIC2
• coagulopathy
• progressive familial intrahepatic cholestasis

• Total internal biliary diversion
• outcomes
• progressive familial intrahepatic cholestasis
• quality of life

• Child
• Humans
• Liver Transplantation
• Disease Progression
• Cholestasis, Intrahepatic/surgery
• Fatty Liver
• Diarrhea

• ABCB4 gene
• Novel variants
• Progress familial intrahepatic cholestasis type 3 (PFIC3)

• clinical decision-making
• clinical research/practice
• intestinal failure/injury
• intestine/multivisceral transplantation
• pediatrics

We analyzed the long-term survival rate and development of progressive familial intrahepatic cholestasis (PFIC) patients after liver transplantation (LT). From October 2007 to May 2019, 41 patients were diagnosed as PFIC (type I-III) and received LT in Ren Ji Hospital due to end-stage liver diseases. The median age at LT was 2.93 years, with 75.6% of patients receiving living donor liver transplantation (LDLT). The 5- and 10-year patient survival rates after LT were 92.7% and 92.7%, respectively, and no difference was found among the three subtypes of PFIC. Two PFIC type II patients received re-transplantation due to vascular complications. Liver function and bile acid metabolism returned to normal levels in all living recipients. Catch-up growth was recorded as the height and weight Z scores increased from −2.53 and −1.54 to −0.55 and −0.27 with a median follow-up time of 5.55 years. Improved psychomotor ability and age-appropriate study ability was also observed. A total of 72.4% of school-aged recipients exhibited average academic performance. Diarrhea was reported in all PFIC type I recipients but resolved after resin absorptive treatment. However, allograft steatosis occurred in one PFIC type I patient and exhibited a “remission–relapse circle” under the treatment of cholestyramine. In conclusion, LT is an effective treatment for end-stage PFIC patients with encouraging long-term survival rate and development. However, allograft steatosis should be closely monitored in PFIC type I patients even if diarrhea has been well treated.

• Carcinoma, Hepatocellular/complications
• Child
• Cholestasis/metabolism
• Humans
• Liver Diseases/etiology
• Liver Diseases/genetics
• Liver Neoplasms/etiology
• Liver Neoplasms/genetics
• Pruritus/etiology

Mutations that occur in the ABCB4 gene, which encodes multidrug-resistant protein 3, underlie the occurrence of progressive familial intrahepatic cholestasis type 3 (PFIC3). Clinical signs of intrahepatic cholestasis due to gene mutations typically first appear during infancy or childhood. Reports of PFIC3 occurring in adults are rare.

This is a case study of a 32-year-old infertile female Chinese patient with a 15-year history of recurrent abnormal liver function. Her primary clinical signs were elevated levels of alkaline phosphatase and γ-glutamyl transpeptidase. Other possible reasons for liver dysfunction were eliminated in this patient, resulting in a diagnosis of PFIC3. The diagnosis was confirmed using gene detection and histological analyses. Assessments using genetic sequencing analysis indicated the presence of two novel heterozygous mutations in the ABCB4 gene, namely, a 2950C>T; p.A984V mutation (exon 24) and a 667A>G; p.I223V mutation (exon 7). After receiving ursodeoxycholic acid (UDCA) treatment, the patient's liver function indices improved, and she successfully became pregnant by in vitro fertilization. However, the patient developed intrahepatic cholestasis of pregnancy in the first trimester. Fortunately, treatment with UDCA was safe and effective.

These novel ABCB4 heterozygous mutations have a variety of clinical phenotypes. Continued follow-up is essential for a comprehensive understanding of PFIC3.

• Progressive familial intrahepatic cholestasis type 3
• ABCB4 gene
• Infertility
• Intrahepatic cholestasis of pregnancy
• Case report

Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare genetic diseases characterized by inadequate bile secretion that requires substantial ongoing care, though little research is published in this area. We report health-related quality of life (HRQoL) and work productivity outcomes from the retrospective, cross-sectional PICTURE study investigating the burden of PFIC on caregivers. Information from caregivers of patients with PFIC 1 or 2 in Germany, the United Kingdom and the United States from September 2020 to March 2021 was included.

The PICTURE study sample comprised HRQoL responses from 22 PFIC caregivers. Patients were on average 8.2 years old; most caregivers were 30–49 years old (68%) and mothers (77%). Median CarerQoL-7D score was 67.7/100; mean CarerQoL-VAS score for general happiness was 5.7/10 (SD 2.1). Most caregivers reported fulfilment in their caregiving responsibilities, but problems with mental and physical health, finances, and relationships. When stratified by patient’s PFIC type, mean CarerQoL-7D and CarerQoL-VAS scores suggested worse HRQoL outcomes with PFIC2 versus PFIC1 (59.4 vs. 71.2, and 5.3 vs. 6.5, respectively). Additionally, more caregivers reported impact on sleep in the PFIC2 versus PFIC1 subgroup (93% vs. 75%). When stratified by history of PFIC-related surgeries, mean CarerQoL-7D and VAS scores were higher among those whose children had no specified surgeries (67.7 vs. 59.0/100 and 6.2 vs. 5.2/10, respectively). Nearly all caregivers reported an impact of caregiving responsibilities on sleeping (86%) and on personal relationships (82%). No caregivers reported having formal care support. Most caregivers were employed (73%); a third reported mean productivity loss of 12.9 days (SD 19.3) over the last 3 months, and a mean of 2.8 (SD 9.5) missed years of employment during their career. A higher number of workdays were missed by PFIC 2 caregivers compared to PFIC1 over last 3 months (16 days vs. 3 days).

The PICTURE study has demonstrated the prevalent, comprehensive, and meaningful burden that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL including mental and physical health, productivity, career prospects, sleep, relationships and finances.

The online version contains supplementary material available at 10.1186/s13023-022-02177-0.

• Caregiver burden
• Employment
• Patient-reported outcomes
• Progressive familial intrahepatic cholestasis
• Work productivity

• Pruritus
• biliary diversion
• cholestasis
• liver transplantation
• progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of genetic autosomal recessive diseases that cause severe cholestasis, which progresses to cirrhosis and liver failure, in infancy or early childhood. We herein report the clinical outcomes of surgical management in patients with four types of PFIC.

Six patients diagnosed with PFIC who underwent surgical treatment between 1998 and 2020 at our institution were retrospectively assessed. Living-donor liver transplantation (LDLT) was performed in 5 patients with PFIC. The median age at LDLT was 4.8 (range: 1.9–11.4) years. One patient each with familial intrahepatic cholestasis 1 (FIC1) deficiency and bile salt export pump (BSEP) deficiency died after LDLT, and the four remaining patients, one each with deficiency of FIC1, BSEP, multidrug resistance protein 3 (MDR3), and tight junction protein 2 (TJP2), survived. One FIC1 deficiency recipient underwent LDLT secondary to deterioration of liver function, following infectious enteritis. Although he underwent LDLT accompanied by total external biliary diversion, the patient died because of PFIC-related complications. The other patient with FIC1 deficiency had intractable pruritus and underwent partial internal biliary diversion (PIBD) at 9.8 years of age, pruritus largely resolved after PIBD. One BSEP deficiency recipient, who had severe graft damage, experienced recurrence of cholestasis due to the development of antibodies against BSEP after LDLT, and eventually died due to graft failure. The other patient with BSEP deficiency recovered well after LDLT and there was no evidence of posttransplant recurrence of cholestasis. In contrast, recipients with MDR3 or TJP2 deficiency showed good courses and outcomes after LDLT.

Although LDLT was considered an effective treatment for PFIC, the clinical courses and outcomes after LDLT were still inadequate in patients with FIC1 and BSEP deficiency. LDLT accompanied by total biliary diversion may not be as effective for patients with FIC1 deficiency.

• Cholestasis
• Liver transplantation
• Pediatrics
• Progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease requiring liver transplantation (LT). The objective of this study was to investigate the clinicopathological features and posttransplant courses of seven LT recipients with PFIC.

This was a retrospective single-center study of patients with PFIC who underwent LT from January 2013 to June 2020.

Two and five patients were diagnosed with PFIC type 1 and type 2, respectively. For all seven patients, age of PFIC onset was at birth. Jaundice was present in all cases. Mean pretransplant total and direct bilirubin levels were 16.1 ± 8.1 mg/dL and 12.4 ± 6.2 mg/dL, respectively. Median patient age and body weight at LT were 10 months and 7 kg, respectively. Types of donors were mothers of patients in four and deceased donors in three. All five patients with PFIC type 2 recovered uneventfully. One patient each with PFIC type 1 underwent retransplantation due to graft failure or died due to multi-organ failure. Overall graft and patient survival rates at five years were 66.7% and 83.3%, respectively. Bile salt export pump immunohistochemical staining showed normal canalicular expression in two patients with PFIC type 1, focal loss in two patients with PFIC type 2, and total loss in three patients with PFIC type 2.

LT is currently the only effective treatment for PFIC-associated end-stage liver diseases. It is mandatory to perform regular follow-up due to the risk of complications including steatohepatitis, especially for patients with PFIC type 1.

Progressive familial intrahepatic cholestasis is a rare, heterogeneous group of liver disorders of autosomal recessive inheritance, characterised by an early onset of cholestasis with pruritus and malabsorption, which rapidly progresses, eventually culminating in liver failure. For children and their parents, PFIC is an extremely distressing disease. Significant pruritus can lead to severe cutaneous mutilation and may affect many activities of daily living through loss of sleep, irritability, poor attention, and impaired school performance.

Databases including MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.

Three systematic reviews and twenty-two studies were eligible for inclusion for the epidemiology of PFIC including a total of 2603 patients. Study periods ranged from 3 to 33 years. Local population prevalence of PFIC was reported in three studies, ranging from 9.0 to 12.0% of children admitted with cholestasis, acute liver failure, or splenomegaly. The most detailed data come from the NAPPED study where native liver survival of >15 years is predicted in PFIC2 patients with a serum bile  acid concentration below 102 µmol/L following bile diversion surgery. Burden of disease was mainly reported through health-related quality of life (HRQL), rates of surgery and survival. Rates of biliary diversion and liver transplant varied widely depending on study period, sample size and PFIC type, with many patients have multiple surgeries and progressing to liver transplant. This renders data unsuitable for comparison.

Using robust and transparent methods, this systematic review summarises our current knowledge of PFIC. The epidemiological overview is highly mixed and dependent on presentation and PFIC subtype. Only two studies reported HRQL and mortality results were variable across different subtypes. Lack of data and extensive heterogeneity severely limit understanding across this disease area, particularly variation around and within subtypes.

The online version contains supplementary material available at 10.1186/s13023-021-01884-4.

• ABCB11
• ABCB4
• ATP8B1
• Bile acid
• NR1H4 and Myo5b
• Pruritus
• TJP2

• ABCB4
• Case report
• MDR3
• Progressive familial intrahepatic cholestasis

• ATP Binding Cassette Transporter, Subfamily B/deficiency
• ATP Binding Cassette Transporter, Subfamily B/genetics
• ATP Binding Cassette Transporter, Subfamily B/immunology
• Adult
• Biological Transport
• Cholestasis, Intrahepatic/genetics
• Cholestasis, Intrahepatic/immunology
• Cholestasis, Intrahepatic/pathology
• Cholestasis, Intrahepatic/surgery
• Female
• Fibrosis/genetics
• Fibrosis/immunology
• Fibrosis/pathology
• Fibrosis/surgery
• Gene Expression
• Genes, Recessive
• Heterozygote
• Humans
• Liver/immunology
• Liver/pathology
• Liver/surgery
• Liver Transplantation
• Phosphatidylcholines/metabolism
• Time Factors

• Canadian Institutes for Health Research
• Canadian Institutes of Health Research
• Canadian Liver Foundation

• ABCB4 deficiency
• Cholangiocarcinoma
• Drug-induced liver injury
• Intrahepatic cholestasis of pregnancy
• Liver fibrosis
• Low phospholipid-associated cholelithiasis
• Progressive familial intrahepatic cholestasis type 3

• ATP Binding Cassette Transporter, Subfamily B/deficiency
• ATP Binding Cassette Transporter, Subfamily B/genetics
• Adult
• Bile Duct Neoplasms/diagnosis
• Bile Duct Neoplasms/drug therapy
• Bile Duct Neoplasms/genetics
• Bile Duct Neoplasms/surgery
• Chemical and Drug Induced Liver Injury/diagnosis
• Chemical and Drug Induced Liver Injury/drug therapy
• Chemical and Drug Induced Liver Injury/genetics
• Chemical and Drug Induced Liver Injury/surgery
• Cholelithiasis/diagnosis
• Cholelithiasis/drug therapy
• Cholelithiasis/genetics
• Cholelithiasis/surgery
• Cholestasis, Intrahepatic/diagnosis
• Cholestasis, Intrahepatic/drug therapy
• Cholestasis, Intrahepatic/genetics
• Cholestasis, Intrahepatic/surgery
• Female
• Gallbladder Neoplasms/diagnosis
• Gallbladder Neoplasms/drug therapy
• Gallbladder Neoplasms/genetics
• Gallbladder Neoplasms/surgery
• Humans
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/genetics
• Liver Cirrhosis/surgery
• Liver Transplantation/methods
• Male
• Polymorphism, Single Nucleotide
• Pregnancy
• Pregnancy Complications/diagnosis
• Pregnancy Complications/drug therapy
• Pregnancy Complications/genetics
• Pregnancy Complications/surgery
• Treatment Outcome
• Ursodeoxycholic Acid/therapeutic use
• Young Adult

Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) are inherited cholestatic disorders with risk of developing end‐stage liver disease requiring liver transplantation (LT). We investigated aspartate aminotransferase‐to‐platelet ratio index (APRI), Fibrosis‐4 score (FIB‐4), and conjugated bilirubin as biomarkers to assess fibrosis severity and risk for LT among children with ALGS and PFIC. This multicenter, cross‐sectional study included 64 children with ALGS or PFIC (per genetics or strict clinical criteria) with APRI, FIB‐4, and conjugated bilirubin levels collected within ±90 days of their most recent liver biopsy. A single, blinded pathologist staged all biopsies (metavir; F0‐F2: nonsevere, F3‐F4: severe). Logistic regression and area under the receiver operating characteristic curve analysis (AUC) were used to assess biomarker associations with fibrosis severity and risk for LT. In ALGS, only APRI distinguished F3‐F4 (AUC 0.72, P = 0.012), with a cutoff greater than 2.97 demonstrating a sensitivity of 61.5% (95% confidence interval 0.32, 0.86) and specificity of 81.5% (0.62, 0.94). In ALGS, a 50% increase of APRI increased the odds of F3‐F4 by 1.31‐fold (1.04, 1.65; P = 0.023). In ALGS, APRI (AUC 0.87; P < 0.001) and FIB‐4 (AUC 0.84; P < 0.001) were able to predict risk for LT. In PFIC, only APRI distinguished F3‐4 (AUC 0.74, P = 0.039), with a cutoff greater than 0.99 demonstrating a sensitivity of 80% (0.44, 0.98) and specificity of 64.3% (0.35, 0.87). In PFIC, only FIB‐4 was able predict risk for LT (AUC 0.80; P = 0.002). In ALGS or PFIC, conjugated bilirubin could not distinguish F3‐F4 or predict risk for LT. Conclusion: This liver biopsy–validated study suggests that APRI is able to distinguish F3‐F4 from F0‐F2 in ALGS and PFIC. APRI and FIB‐4 may also serve as predictors of risk for LT in ALGS (APRI and FIB‐4) and PFIC (FIB‐4).

• AAV
• AAV8
• ABCB4
• Adeno-associated virus
• Correction cholestatic phenotype
• Gene therapy
• MDR2
• MDR3
• PFIC type 3
• PFIC3
• Progressive familial intrahepatic cholestasis

• ATP Binding Cassette Transporter, Subfamily B/deficiency
• ATP Binding Cassette Transporter, Subfamily B/genetics
• ATP Binding Cassette Transporter, Subfamily B/metabolism
• Animals
• Bile/metabolism
• Cholestasis, Intrahepatic/genetics
• Cholestasis, Intrahepatic/therapy
• Dependovirus
• Genetic Therapy/methods
• Liver Cirrhosis/metabolism
• Mice
• Mice, Transgenic
• Phospholipids/metabolism
• Secretory Pathway/physiology
• ATP-Binding Cassette Sub-Family B Member 4

• ABCB11
• ATP8B1
• Bile salt export pump
• Progressive familial intrahepatic cholestasis

• Biliary tract diseases
• Cirrhosis
• Inflammatory bowel disease (IBD)
• Metabolic bone disease
• Primary biliary cholangitis (PBC)
• Primary sclerosing cholangitis (PSC)
• Prophylaxis
• Pruritus

• UL1 TR000135 NCATS NIH HHS

• ABCB11
• ABCB4
• ATP8B1
• Bile secretion
• Byler’s disease
• Pruritus

Progressive familial intrahepatic cholestasis type 3 is caused by a mutation in the ATP-binding cassette, subfamily B, member 4 (ABCB4) gene encoding multidrug resistance protein 3. A 32-year-old woman with a history of acute hepatitis at age 9 years was found to have jaundice during pregnancy in 2008, and was diagnosed as having intrahepatic cholestasis of pregnancy. In 2009, she underwent cholecystectomy for gallstones and chronic cholecystitis. However, itching and jaundice did not resolve postoperatively. She was admitted to our hospital with fatigue, jaundice, and a recently elevated γ-glutamyl transpeptidase level. Liver biopsy led to the diagnosis of biliary cirrhosis with ductopenia. Genetic testing revealed a pathogenic heterozygous mutation, ex13 c.1531G > A (p.A511T), in the ABCB4 gene. Her father did not carry the mutation, but her mother’s brother carried the heterozygous mutation. We made a definitive diagnosis of familial intrahepatic cholestasis type 3. Her symptoms and liver function improved after 3 mo of treatment with ursodeoxycholic acid.

• Cirrhosis
• Progressive familial intrahepatic cholestasis type 3
• Case report

• ATP Binding Cassette Transporter, Subfamily B/deficiency
• ATP Binding Cassette Transporter, Subfamily B/genetics
• Adult
• Bile Ducts, Intrahepatic/pathology
• Biopsy
• Cholestasis, Intrahepatic/diagnosis
• Cholestasis, Intrahepatic/drug therapy
• Cholestasis, Intrahepatic/genetics
• Cholestasis, Intrahepatic/pathology
• DNA Mutational Analysis
• Female
• Genetic Testing
• Humans
• Liver/pathology
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/genetics
• Liver Cirrhosis/pathology
• Ursodeoxycholic Acid/therapeutic use
• gamma-Glutamyltransferase/blood

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive cholestatic liver diseases which are subgrouped according to the genetic defect, clinical presentation, laboratory findings and liver histology. Progressive liver fibrosis, cirrhosis, and end stage liver disease (ESLD) may eventually develop. PFIC was first described in Amish descendants of Jacob Byler, therefore it was originally called Byler disease. But it can be seen anywhere on the globe. This review summarizes the main features of the subtypes of the disease and discusses the current available diagnosis, conservative and surgical therapeutic options.

• biliary diversion
• intrahepatic cholestasis
• jaundice

• canalicular ectoenzymes
• canalicular transport proteins
• cholestasis
• congenital hypopituitarism
• septo-optic dysplasia

• Liver
• Pediatric
• Split liver
• Transplant

• Biliary atresia
• Cholestasis
• Jaundice
• Neonatal cholestasis
• Neonatal liver disease

• low-GGT PFIC
• neonatal cholestasis
• progressive familial intrahepatic cholestasis
• progressive familial intrahepatic cholestasis type 2
• γ-glutamyl transferase

• Bile acids
• Liver transplantation
• Partial external biliary drainage
• Progressive familial intrahepatic cholestasis (PFIC) C

• ABCB11 gene
• PFIC recurrence
• canalicular antibodies
• children
• rituximab

• inborn errors of metabolism
• long-term follow-up
• pediatric liver transplantation
• perioperative management

Progressive familial intrahepatic cholestasis (PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described.

• Pediatric liver transplant
• Progressive familial intrahepatic cholestasis
• Familial intrahepatic cholestasis protein 1
• Cholestasis
• Multidrug resistance protein 3
• Pediatric jaundice
• Bile salt excretion protein

• ABC, ATP binding cassette
• ASBT, apical sodium bile salt transporter
• ATP, adenosine triphosphate
• ATPase, adenosine triphosphatase
• BRIC, benign recurrent intrahepatic cholestasis
• BSEP, bile salt exporter protein
• CFTR, cystic fibrosis transmembrane conductance regulator
• CYP, cytochrome P
• DNA, deoxyribonucleic acid
• ERAD, endoplasmic reticulum associated degradation
• ESLD, end stage liver disease
• FIC1, familial intrahepatic cholestasis protein 1
• FXR, farnesoid X receptor
• HCC, hepatocellular carcinoma
• IB, ileal bypass
• ICP, intrahepatic cholestasis of pregnancy
• LT, liver transplant
• MARS, Molecular Adsorbent Recirculating System
• MDR, multidrug resistance protein
• MRCP, magnetic resonance cholangiopancreaticography
• PBD, partial biliary drainage
• PEBD, partial external biliary drainage
• PFIC, progressive familial intrahepatic cholestasis
• PIBD, partial internal biliary drainage
• PPAR, peroxisome proliferator activator receptor
• UDCA, ursodeoxycholic acid
• bile secretion
• children
• cholestasis
• familial
• mRNA, messenger ribonucleic acid
• pGp, p-glycoprotein
• pruritus

• ATP Binding Cassette Transporter, Subfamily B, Member 11
• ATP-Binding Cassette Transporters/deficiency
• ATP-Binding Cassette Transporters/genetics
• ATP-Binding Cassette Transporters/immunology
• Antibodies/blood
• Antibodies, Monoclonal, Murine-Derived/therapeutic use
• Biopsy
• Cholestasis, Intrahepatic/blood
• Cholestasis, Intrahepatic/diagnosis
• Cholestasis, Intrahepatic/genetics
• Cholestasis, Intrahepatic/immunology
• Cholestasis, Intrahepatic/surgery
• Genetic Predisposition to Disease
• Humans
• Immunoglobulin G/blood
• Immunoglobulins, Intravenous/therapeutic use
• Immunosuppressive Agents/therapeutic use
• Infant
• Liver Transplantation
• Male
• Phenotype
• Plasmapheresis
• Recurrence
• Rituximab
• Time Factors
• Treatment Outcome

• Genetic diseases
• Inborn
• Liver transplantation
• Metabolic diseases
• Rare diseases
• Surgical gene therapy

• Adolescent
• Bile Acids and Salts/blood
• Biliary Tract Surgical Procedures/methods
• Biomarkers/blood
• Child
• Child, Preschool
• Cholestasis, Intrahepatic/blood
• Cholestasis, Intrahepatic/complications
• Cholestasis, Intrahepatic/surgery
• Female
• Follow-Up Studies
• Humans
• Infant
• Liver Cirrhosis/etiology
• Liver Cirrhosis/surgery
• Liver Transplantation
• Male
• Ostomy
• Retrospective Studies
• Risk Factors
• Treatment Outcome

• Adolescent
• Adult
• Child
• Child, Preschool
• Cholestasis, Intrahepatic/surgery
• Disease Progression
• Female
• Humans
• Infant
• Liver Transplantation/adverse effects
• Living Donors
• Male
• Middle Aged
• Postoperative Complications/epidemiology