A colestase intra-hepática familiar progressiva tipo 2 (PFIC2), um tipo de colestase intra-hepática familiar progressiva (PFIC), é um distúrbio hereditário neonatal grave na formação da bile de origem hepatocelular e não associado a características extra-hepáticas. Inicialmente, a PFIC2 foi relatada sob o nome de síndrome de Byler.
Introdução
O que você precisa saber de cara
A colestase intra-hepática familiar progressiva tipo 2 (PFIC2), um tipo de colestase intra-hepática familiar progressiva (PFIC), é um distúrbio hereditário neonatal grave na formação da bile de origem hepatocelular e não associado a características extra-hepáticas. Inicialmente, a PFIC2 foi relatada sob o nome de síndrome de Byler.
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 8 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 16 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
1 gene identificado com associação a esta condição. Padrão de herança: Autosomal recessive.
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, Pub
Apical cell membraneRecycling endosome membraneEndosomeCell membrane
Cholestasis, progressive familial intrahepatic, 2
A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC2 inheritance is autosomal recessive.
Medicamentos e terapias
Mecanismo: Ileal bile acid transporter inhibitor
Variantes genéticas (ClinVar)
451 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 521 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
3 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Colestase intra-hepática progressiva familiar tipo 2
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Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Ensaios em destaque
Pesquisa e ensaios clínicos
3 ensaios clínicos encontrados.
Publicações mais relevantes
Bortezomib Therapy in Autoimmune-BSEP Disease After Liver Transplantation: Case Report With Review of the Literature.
Progressive familial intrahepatic cholestasis type 2 (PFIC-2) is a rare autosomal recessive disorder caused by mutations in the ABCB11 gene, which encodes the bile salt export pump (BSEP). Liver transplantation is the standard treatment for end-stage liver disease in PFIC-2; however, recurrence in the form of autoimmune BSEP disease (AIBD) is a recognized posttransplant complication. AIBD is characterized by cholestasis with normal gamma-glutamyl transpeptidase, severe pruritus, and the presence of anti-BSEP antibodies. We report a case of a PFIC-2 patient who developed recurrent cholestasis and pruritus three years posttransplant. Liver biopsy revealed canalicular cholestasis and giant cell transformation, while BSEP staining on immunohistochemistry was preserved. Serological testing confirmed anti-BSEP antibody positivity. Despite aggressive therapy including plasmapheresis, intravenous immunoglobulin, and rituximab, only partial improvement was achieved, and cholestasis persisted. Given the refractory nature of the disease, bortezomib-a proteasome inhibitor targeting antibody-producing plasma cells-was administered. The patient demonstrated complete clinical and biochemical resolution following bortezomib therapy. This case highlights the diagnostic complexity of AIBD and the potential role of bortezomib in cases unresponsive to conventional immunosuppressive therapies. Early diagnosis and personalized immunomodulation remain key to improving outcomes in this rare but challenging condition.
Pretreatment serum bile acid composition and predictability of subsequent response to odevixibat in patients with bile salt export pump (BSEP) deficiency.
Bile salt export pump (BSEP) deficiency, or progressive familial intrahepatic cholestasis type 2, is a genetic liver disease characterized by defective biliary bile acid secretion. Odevixibat, an ileal bile acid transporter inhibitor (IBATi), impairs intestinal reabsorption of conjugated bile acids, reducing serum bile acid (sBA) concentration in some patients with BSEP deficiency. We evaluated the association of pretreatment sBA levels and composition, as well as the subsequent response to odevixibat in patients with BSEP deficiency, to improve our understanding of the mechanism. In this blinded post hoc analysis, pretreatment sBAs from 41 odevixibat-treated patients with BSEP deficiency who participated in PEDFIC were analyzed using liquid chromatography-tandem mass spectrometry. Patients were divided into sBA responders (Rs) and non-responders (NRs). Association of pretreatment individual sBAs with subsequent response was evaluated, and receiver operating characteristic (ROC) curves were constructed to identify discriminating cutoff values. Rs had higher pretreatment percentages of unconjugated cholic acid [CA; area under the ROC curve (AUC): 0.70 (95% CI: 0.52-0.87; p =0.03)], unconjugated chenodeoxycholic acid [CDCA; AUC: 0.73 (0.56-0.90); p =0.01], and concentration of CA + CDCA [AUC: 0.76 (0.61-0.92); p =0.001]. When ≥1 of 3 cutoffs were reached, 36/41 (87.8%) patients with BSEP deficiency were correctly classified as subsequent Rs (17/19; sensitivity: 89.5%) or NRs (19/22; specificity: 86.4%). Higher pretreatment serum levels of unconjugated CA and CDCA are associated with subsequent response to odevixibat in patients with BSEP deficiency. Response to odevixibat may be related to residual biliary bile acid secretion capacity in patients with BSEP deficiency.
Long-Term Management of Recurrent Antibody-Induced Bile Salt Export Pump Deficiency After Liver Transplantation Using Therapeutic Plasma Exchange.
Progressive Familial Intrahepatic Cholestasis type 2 (PFIC-2) is a rare autosomal recessive liver disorder caused by ABCB11 mutations impairing the bile salt export pump (BSEP). Liver transplantation is typically considered curative; however, a subset of patients develop antibody-induced BSEP deficiency (AIBD), a rare post-transplant complication driven by recipient IgG antibodies against graft BSEP. Patients often present with recurrent cholestasis and graft dysfunction. Therapeutic plasma exchange (TPE) is increasingly used to remove circulating antibodies, often alongside immunomodulatory therapies. We describe a patient with PFIC-2 who developed four distinct AIBD relapses over a 24-year period, beginning 12 years after transplantation. Each relapse was treated with a coordinated regimen including TPE, intravenous immunoglobulin (IVIg), rituximab, and optimized maintenance immunosuppression. TPE procedures were performed using the Spectra Optia system with one plasma volume exchange using citrate anticoagulation. Across all relapses, TPE was associated with rapid reductions in cholestatic markers, with the greatest improvements noted after apheresis initiation. TPE procedure intensity evolved over time, with earlier initiation and a gradual increase in the total number of exchanges per relapse. Biopsies demonstrated progressive cholestatic injury, yet graft function remained preserved and re-transplantation was avoided. Adverse events were infrequent and managed conservatively. This case highlights the potential role of early and sustained use of TPE as part of a multimodal strategy for managing recurrent AIBD. Consistent clinical and biochemical improvement across relapses supports incorporating TPE with immunosuppression and B-cell targeted therapy in similar presentations. Further studies are needed to clarify optimal timing, frequency, and treatment combinations.
Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2.
Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a severe hepatocellular cholestasis due to biallelic variations in the ABCB11 (ATP-binding cassette B11) gene encoding the canalicular bile salt export pump (BSEP). Some missense variants identified in patients with PFIC2 do not traffic properly to the canalicular membrane. However, 4-phenybutyrate (4-PB) has been shown in vitro to partially correct the mis-trafficking of selected variants, resulting in an improvement of the medical conditions of corresponding PFIC2 patients. Herein, we report the ability of 4-PB analogous or homologous drugs and of non-4-PB related chemical correctors to rescue the canalicular expression and the activity of the folding-defective Abcb11R1128C variant. New compounds, either identified by screening a chemical library or designed by structural homology with 4-PB (or its metabolites) and synthesized, were evaluated in vitro for their ability to (i) correct the canalicular localization of Abcb11R1128C after transfection in hepatocellular polarized cell lines; (ii) restore the 3H-taurocholate transport of the Abcb11R1128C protein in Madin-Darby canine kidney (MDCK) cells stably co-expressing Abcb11 and the sodium taurocholate co-transporting polypeptide (Ntcp/Slc10A1). Glycerol phenylbutyrate (GPB), phenylacetate (PA, the active metabolite of 4-PB), 3-hydroxy-2-methyl-4-phenylbutyrate (HMPB, a 4-PB metabolite analog chemically synthesized in our laboratory) and 4-oxo-1,2,3,4-tetrahydro-naphthalene-carboxylate (OTNC, from the chemical library screening) significantly increased the proportion of canalicular Abcb11R1128C protein. GPB, PA, ursodeoxycholic acid (UDCA), alone or in combination with 4-PB, suberoylanilide hydroxamic acid (SAHA), C18, VX-445, and/or VX-661, significantly corrected both the traffic and the activity of Abcb11R1128C. Such correctors could represent new pharmacological insights for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the transporter's traffic.
Retraction: Progressive Familial Intrahepatic Cholestasis Type 2 in an Infant: Diagnostic Challenges and Multidisciplinary Management.
[This retracts the article DOI: 10.7759/cureus.76355.].
Publicações recentes
Long-Term Management of Recurrent Antibody-Induced Bile Salt Export Pump Deficiency After Liver Transplantation Using Therapeutic Plasma Exchange.
Bortezomib Therapy in Autoimmune-BSEP Disease After Liver Transplantation: Case Report With Review of the Literature.
Exploring Maralixibat for Treatment-Resistant Pruritus in Intrahepatic Cholestasis of Pregnancy and Primary Biliary Cholangitis: A Case Report.
Case Report: Genetic predisposition to low-dose NSAID-induced liver injury in real-world China.
📚 EuropePMC31 artigos no totalmostrando 67
Long-Term Management of Recurrent Antibody-Induced Bile Salt Export Pump Deficiency After Liver Transplantation Using Therapeutic Plasma Exchange.
Journal of clinical apheresisBortezomib Therapy in Autoimmune-BSEP Disease After Liver Transplantation: Case Report With Review of the Literature.
Journal of clinical and experimental hepatologyExploring Maralixibat for Treatment-Resistant Pruritus in Intrahepatic Cholestasis of Pregnancy and Primary Biliary Cholangitis: A Case Report.
The American journal of case reportsCase Report: Genetic predisposition to low-dose NSAID-induced liver injury in real-world China.
Frontiers in medicinePretreatment serum bile acid composition and predictability of subsequent response to odevixibat in patients with bile salt export pump (BSEP) deficiency.
Hepatology (Baltimore, Md.)An ABCB11 variant registry and novel knockin mouse model of PFIC2 based on the clinically relevant ABCB11 E297G variant.
Journal of lipid researchA structural and mechanistic model for BSEP dysfunction in PFIC2 cholestatic disease.
Communications biologyProgressive Familial Intrahepatic Cholestasis Type 2 in an Infant: Diagnostic Challenges and Multidisciplinary Management.
CureusHepatocellular carcinoma associated with progressive intrahepatic familial cholestasis type 2: a case report.
Clinical transplantation and researchThe spectrum of novel ABCB11 gene variations in children with progressive familial intrahepatic cholestasis type 2 in Pakistani cohorts.
Scientific reportsClinical symptoms, biochemistry, and liver histology during the native liver period of progressive familial intrahepatic cholestasis type 2.
Orphanet journal of rare diseasesPlasma Concentration of Antifungal Agent Micafungin for Pediatric Living Donor Liver Transplantation.
Transplantation proceedingsCell-based BSEP trans-inhibition: A novel, non-invasive test for diagnosis of antibody-induced BSEP deficiency.
JHEP reports : innovation in hepatologyIterative antibody-induced bile salt export pump deficiency after successive liver transplantations successfully treated with plasmapheresis and rituximab.
Clinics and research in hepatology and gastroenterologyGenotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency.
JHEP reports : innovation in hepatologyABO-incompatible Pediatric Liver Transplantation With Antibody and B-cell Depletion-free Immunosuppressive Protocol in High Consanguinity Communities.
Transplantation directIn Vitro Rescue of the Bile Acid Transport Function of ABCB11 Variants by CFTR Potentiators.
International journal of molecular sciencesProgressive Familial Intrahepatic Cholestasis Type 2 and Recurrence After Liver Transplantation: A Case Report.
Transplantation proceedingsAntisense oligonucleotides rescue an intronic splicing variant in the ABCB11 gene that causes progressive familial intrahepatic cholestasis type 2.
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the LiverSeventeen Years of Pediatric Liver Transplantation Experience for Cirrhosis and Hepatocellular Carcinoma.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ TransplantationA study of exons 14, 15, and 24 of the ABCB11 gene in Egyptian children with normal GGT cholestasis.
Arab journal of gastroenterology : the official publication of the Pan-Arab Association of GastroenterologyIn vitro functional rescue by ivacaftor of an ABCB11 variant involved in PFIC2 and intrahepatic cholestasis of pregnancy.
Orphanet journal of rare diseasesClinical spectrum of chronic liver disease with final outcome in children at a tertiary centre: A single - centre study.
Pakistan journal of medical sciencesTransient hyperphosphatasemia following pediatric liver transplantation in a patient with hepatic and skeletal abnormalities.
Clinica chimica acta; international journal of clinical chemistryGlibenclamide, ATP and metformin increases the expression of human bile salt export pump ABCB11.
F1000Research[Clinical characteristics and gene variants of patients with infantile intrahepatic cholestasis].
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatricsThe Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies.
International journal of molecular sciencesGraft outflow vein venoplasty for a laparoscopically harvested left lateral section graft in pediatric living donor liver transplantation.
Korean journal of transplantationPharmacological Premature Termination Codon Readthrough of ABCB11 in Bile Salt Export Pump Deficiency: An In Vitro Study.
Hepatology (Baltimore, Md.)Coexistence of Three Different Mutations in a Male Infant: neurofibromatosis Type 1, Progressive Familial Intrahepatic Cholestasis Type 2 and LPIN3.
Fetal and pediatric pathologyTreatment of rickets and dyslipidemia in twins with progressive familial intrahepatic cholestasis type 2.
International journal of pediatric endocrinologyGlycerol Phenylbutyrate Therapy in Progressive Familial Intrahepatic Cholestasis Type 2.
Journal of pediatric gastroenterology and nutritionFunctional rescue of an ABCB11 mutant by ivacaftor: A new targeted pharmacotherapy approach in bile salt export pump deficiency.
Liver international : official journal of the International Association for the Study of the LiverChanges in plasma bile acid profiles after partial internal biliary diversion in PFIC2 patients.
Annals of translational medicineClinical profiles and diagnostic challenges in 1158 children with rare hepatobiliary disorders.
Pediatric researchSuccessful Treatment with Rituximab and Immunoadsorption for an Auto-Antibody Induced Bile Salt Export Pump Deficiency in a Liver Transplanted Patient.
Pediatric gastroenterology, hepatology & nutritionLong-term follow-up in children with progressive familial intrahepatic cholestasis type 2 after partial external biliary diversion with focus on histopathological features.
Polish journal of pathology : official journal of the Polish Society of PathologistsPhenotype-Genotype Correlation of North Indian Progressive Familial Intrahepatic Cholestasis type2 Children Shows p.Val444Ala and p.Asn591Ser Variants and Retained BSEP Expression.
Fetal and pediatric pathologyDiagnostic Yield of an Algorithm for Neonatal and Infantile Cholestasis Integrating Next-Generation Sequencing.
The Journal of pediatricsBeyond an Obvious Cause of Cholestasis in a Toddler: Compound Heterozygosity for ABCB11 Mutations.
PediatricsDrugs and hepatic transporters: A review.
Pharmacological researchFirst report of successful transplantation of a pediatric donor liver graft after hypothermic machine perfusion.
Pediatric transplantationTwo Cases of Progressive Familial Intrahepatic Cholestasis Type 2: Role of Surgery with Brief Review of Literature.
Journal of Indian Association of Pediatric SurgeonsHydrophilic bile acids prevent liver damage caused by lack of biliary phospholipid in Mdr2-/- mice.
Journal of lipid researchSurgical management of children and adolescents with upfront completely resected hepatocellular carcinoma.
Pediatric blood & cancerClinical phenotype and molecular analysis of a homozygous ABCB11 mutation responsible for progressive infantile cholestasis.
Journal of human geneticsZebrafish abcb11b mutant reveals strategies to restore bile excretion impaired by bile salt export pump deficiency.
Hepatology (Baltimore, Md.)Post-transplant Recurrent Bile Salt Export Pump Disease: A Form of Antibody-mediated Graft Dysfunction and Utilization of C4d.
Journal of pediatric gastroenterology and nutritionPartial external biliary diversion in bile salt export pump deficiency: Association between outcome and mutation.
World journal of gastroenterologyProgressive Familial Intrahepatic Cholestasis Type 2 in an Indian Child.
Journal of pediatric geneticsA Rare BSEP Mutation Associated with a Mild Form of Progressive Familial Intrahepatic Cholestasis Type 2.
Annals of hepatologyGeneration of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells.
Scientific reportsLiver Transplantation as a Treatment for Severe Refractory Vitamin E Deficiency Related to Progressive Familial Intrahepatic Cholestasis Type 2 in a Pediatric Patient.
ACG case reports journalRecurrence of Progressive Familial Intrahepatic Cholestasis Type 2 Phenotype After Living-donor Liver Transplantation: A Case Report.
Transplantation proceedings[One case of progressive familial intrahepatic cholestasis type 2].
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatologyBipolar and Related Disorders Induced by Sodium 4-Phenylbutyrate in a Male Adolescent with Bile Salt Export Pump Deficiency Disease.
Psychiatry investigationBeneficial Effects of Sodium Phenylbutyrate Administration during Infection with Salmonella enterica Serovar Typhimurium.
Infection and immunityVisceral symptoms as a key diagnostic sign for the early infantile form of Niemann-Pick disease type C in a Russian patient: a case report.
Journal of medical case reportsExon-skipping and mRNA decay in human liver tissue: molecular consequences of pathogenic bile salt export pump mutations.
Scientific reportsSerum Autotaxin Activity Correlates With Pruritus in Pediatric Cholestatic Disorders.
Journal of pediatric gastroenterology and nutritionBile salt export pump-reactive antibodies form a polyclonal, multi-inhibitory response in antibody-induced bile salt export pump deficiency.
Hepatology (Baltimore, Md.)Brucella infection in a child with progressive familial intrahepatic cholestasis type 2 who had undergone liver transplantation.
Pediatric transplantationSuccessful pregnancy after ileal exclusion in progressive familial intrahepatic cholestasis type 2.
Annals of hepatologyTwo Case Reports of Successful Treatment of Cholestasis With Steroids in Patients With PFIC-2.
PediatricsRetargeting of bile salt export pump and favorable outcome in children with progressive familial intrahepatic cholestasis type 2.
Hepatology (Baltimore, Md.)Targeted pharmacotherapy in progressive familial intrahepatic cholestasis type 2: Evidence for improvement of cholestasis with 4-phenylbutyrate.
Hepatology (Baltimore, Md.)The mechanism of increased biliary lipid secretion in mice with genetic inactivation of bile salt export pump.
American journal of physiology. Gastrointestinal and liver physiologyAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Bortezomib Therapy in Autoimmune-BSEP Disease After Liver Transplantation: Case Report With Review of the Literature.
- Pretreatment serum bile acid composition and predictability of subsequent response to odevixibat in patients with bile salt export pump (BSEP) deficiency.
- Long-Term Management of Recurrent Antibody-Induced Bile Salt Export Pump Deficiency After Liver Transplantation Using Therapeutic Plasma Exchange.
- Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2.
- Retraction: Progressive Familial Intrahepatic Cholestasis Type 2 in an Infant: Diagnostic Challenges and Multidisciplinary Management.
- Exploring Maralixibat for Treatment-Resistant Pruritus in Intrahepatic Cholestasis of Pregnancy and Primary Biliary Cholangitis: A Case Report.
- Case Report: Genetic predisposition to low-dose NSAID-induced liver injury in real-world China.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:79304(Orphanet)
- OMIM OMIM:601847(OMIM)
- MONDO:0011156(MONDO)
- GARD:1288(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q60195065(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
