# Colestase intra-hepática progressiva familiar

> Página oficial: https://raras.org/doenca/colestase-intra-hepatica-progressiva-familiar
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 172 — https://www.orpha.net/en/disease/detail/172
- **CID-10**: K76.8
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A colestase intra-hepática familiar progressiva (PFIC) refere-se a um grupo heterogéneo de patologias autossómicas recessivas da infância que perturbam a formação de bilis e apresentam-se com colestase de origem hepatocelular.

## Epidemiologia e herança

- **Prevalência**: Unknown
- **Padrão de herança**: Autosomal recessive

## Sinais e sintomas (101 fenótipos HPO)

- **Anemia** — HPO: HP:0001903
- **Icterícia intermitente** — HPO: HP:0001046
- **Icterícia neonatal prolongada** — HPO: HP:0006579
- **Inflamação portal** — HPO: HP:0033196
- **Pancreatite** — HPO: HP:0001733
- **Fibrose portal** — HPO: HP:0006580
- **Aumento da bilirrubina total** — HPO: HP:0003573
- **Hidropsia fetal não imune** — HPO: HP:0001790
- **Hipoglicemia** — HPO: HP:0001943
- **Derrame pleural** — HPO: HP:0002202
- **Hipertensão** — HPO: HP:0000822
- **Aumento da ecogenicidade hepática** — HPO: HP:0031141
- **Trombose da veia porta** — HPO: HP:0030242
- **Desconforto respiratório** — HPO: HP:0002098
- **Glomerulosclerose global** — HPO: HP:0004737
- **Doença renal crônica estágio 5** — HPO: HP:0003774
- **Ascite** — HPO: HP:0001541
- **Cirrose biliar** — HPO: HP:0002613
- **Hipercolesterolemia** — HPO: HP:0003124
- **Proliferação do ducto biliar** — HPO: HP:0001408
- **Colangite esclerosante** — HPO: HP:0030991
- **Variz esofágica** — HPO: HP:0002040
- **Tempo de protrombina prolongado** — HPO: HP:0008151
- **Alfa-fetoproteína elevada** — HPO: HP:0006254
- **Hiperamonemia** — HPO: HP:0001987
- **Raquitismo** — HPO: HP:0002748
- **Osteopenia** — HPO: HP:0000938
- **Sibilos** — HPO: HP:0030828
- **Epistaxe** — HPO: HP:0000421
- **Colelitíase** — HPO: HP:0001081
- **Colestase intra-hepática com icterícia episódica** — HPO: HP:0006575
- **Hiperbilirrubinemia** — HPO: HP:0002904
- **Cirrose micronodular** — HPO: HP:0001413
- **Proteinúria** — HPO: HP:0000093
- **Febre** — HPO: HP:0001945
- **Diarreia** — HPO: HP:0002014
- **Malformação da placa ductal hepática** — HPO: HP:0006563
- **Concentração anormal de bilirrubina circulante** — HPO: HP:0033479
- **Tempo de tromboplastina parcial prolongado** — HPO: HP:0003645
- **Lesão fibro-obliterativa do ducto biliar** — HPO: HP:0034328
- _...e mais 61 sintomas. Ver https://raras.org/doenca/colestase-intra-hepatica-progressiva-familiar._

## Genes associados (14)

- **TJP2** — Tight junction protein 2 [Disease-causing germline mutation(s) in]
  - Função: Plays a role in tight junctions and adherens junctions (By similarity). Acts as a positive regulator of RANKL-induced osteoclast differentiation, potentially via mediating downstream transcriptional a
- **UTP4** — U3 small nucleolar RNA-associated protein 4 homolog [Candidate gene tested in]
  - Função: Ribosome biogenesis factor. Involved in nucleolar processing of pre-18S ribosomal RNA. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the
- **SEMA7A** — Semaphorin-7A [Disease-causing germline mutation(s) in]
  - Função: Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses. Promotes formation of focal adhesion complexes, activation of the protein k
- **ZFYVE19** — Abscission/NoCut checkpoint regulator [Disease-causing germline mutation(s) in]
  - Função: Key regulator of abscission step in cytokinesis: part of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and
- **ATP8B1** — Phospholipid-transporting ATPase IC [Disease-causing germline mutation(s) in]
  - Função: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of phospholipids, in particular phosphatidylcholines (PC), from the outer to the inne
- **SLC51A** — Organic solute transporter subunit alpha [Disease-causing germline mutation(s) in]
  - Função: Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood (PubMed:163
- **MYO5B** — Unconventional myosin-Vb [Disease-causing germline mutation(s) in]
  - Função: May be involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation. Required in
- **PSKH1** — Serine/threonine-protein kinase H1 [Disease-causing germline mutation(s) in]
  - Função: Serine/threonine protein kinase that may be involved in the regulation of pre-mRNA processing. It may phosphorylate components of nuclear splice factor compartments (SFC), such as non-snRNP splicing f
- **ABCB4** — Phosphatidylcholine translocator ABCB4 [Disease-causing germline mutation(s) in]
  - Função: Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the
- **KIF12** — Kinesin-like protein KIF12 [Disease-causing germline mutation(s) in]
  - Função: Involved in the negative regulation of fatty acid biosynthesis, probably acting as an adapter that allows ubiquitination of acetyl-CoA carboxylase 1 (ACACA) by E3 ubiquitin-protein ligase COP1, and pr
- **NR1H4** — Bile acid receptor [Disease-causing germline mutation(s) in]
  - Função: Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in
- **ABCB11** — Bile salt export pump [Disease-causing germline mutation(s) in]
  - Função: 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 par
- **USP53** — Ubiquitin carboxyl-terminal hydrolase 53 [Disease-causing germline mutation(s) in]
  - Função: Deubiquitinase that mediates 'Lys-63'-linked deubiquitination of tight junction proteins, such as MARVELD2 and LSR, and which is involved in the survival of auditory hair cells and hearing (PubMed:321
- **VPS33B** — Vacuolar protein sorting-associated protein 33B [Disease-causing germline mutation(s) in]
  - Função: May play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes. Required for proper trafficking and targeting of

## Medicamentos em desenvolvimento (2)

- ODEVIXIBAT — Fase Phase 3 (Ileal bile acid transporter inhibitor)
- MARALIXIBAT — Fase Phase 3 (Ileal bile acid transporter inhibitor)
- Fonte: https://platform.opentargets.org/disease/MONDO_0015762

## Ensaios clínicos ativos (11)

- **NCT07191704** [RECRUITING]: 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 — https://clinicaltrials.gov/study/NCT07191704
- **NCT07185919** [RECRUITING]: A Study of the Effectiveness, Safety and the Long-term Outcomes of Participants With Progressive Familial Intrahepatic Cholestasis (PFIC) Who Take Odevixibat (Bylvay) in South Korea — https://clinicaltrials.gov/study/NCT07185919
- **NCT07317193** [RECRUITING]: DEFINING THE GENETIC DRIVERS OF ADULT-ONSET CHOLESTATIC LIVER DISEASE — https://clinicaltrials.gov/study/NCT07317193
- **NCT07293897** [RECRUITING]: A Database Study of Maralixibat (TAK-625) in Participants With Alagille Syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC) — https://clinicaltrials.gov/study/NCT07293897
- **NCT06193928** [RECRUITING]: Long-Term SafEty and Clinical Outcomes of LivmArli in Patients in the United States (LEAP-US) — https://clinicaltrials.gov/study/NCT06193928
- **NCT06778174** [RECRUITING]: Prospective Analysis of the Treatment of Progressive Familial Intrahepatic Cholestasis (TreatFIC) — https://clinicaltrials.gov/study/NCT06778174
- **NCT06781242** [RECRUITING]: Genotype-phenotype Relationship Between Cryptogenic Cholestasis and Familial Intrahepatic Cholestasis — https://clinicaltrials.gov/study/NCT06781242
- **NCT06777914** [RECRUITING]: Familial Intrahepatic Cholestasis-related Genes Associated with Disease Susceptibility in Hepato-biliary Cancers — https://clinicaltrials.gov/study/NCT06777914
- **NCT03930810** [ENROLLING_BY_INVITATION]: NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion — https://clinicaltrials.gov/study/NCT03930810
- **NCT07497724** [NOT_YET_RECRUITING]: Retrospective Observational Study of Odevixibat Outcomes in Patients With PFIC Versus an External Control Cohort (OvEC-PFIC) — https://clinicaltrials.gov/study/NCT07497724

## Doenças relacionadas (por similaridade fenotípica)

- [Alteração do metabolismo e excreção de bilirrubina](https://raras.org/doenca/alteracao-do-metabolismo-e-excrecao-de-bilirrubina) — ORPHA:309816 — 101 sintomas em comum
- [Colestase intra-hepática familiar](https://raras.org/doenca/colestase-intra-hepatica-familiar) — ORPHA:284385 — 101 sintomas em comum
- [Neuro-hepatopatia de Navajo](https://raras.org/doenca/neuro-hepatopatia-de-navajo) — ORPHA:255229 — 37 sintomas em comum
- [Defeito congênito da síntese de ácidos biliares](https://raras.org/doenca/485631) — ORPHA:485631 — 34 sintomas em comum
- [Citrulinemia](https://raras.org/doenca/citrulinemia) — ORPHA:187 — 31 sintomas em comum
- [Colangite esclerosante](https://raras.org/doenca/colangite-esclerosante) — ORPHA:447771 — 31 sintomas em comum
- [Doença renal cística genética](https://raras.org/doenca/doenca-renal-cistica-genetica) — ORPHA:93587 — 30 sintomas em comum
- [Deficiência de citrina](https://raras.org/doenca/deficiencia-de-citrina) — ORPHA:247582 — 30 sintomas em comum
- [Deficiência de lipase ácida lisossomal](https://raras.org/doenca/deficiencia-de-lipase-acida-lisossomal) — ORPHA:275761 — 28 sintomas em comum
- [Porfiria hepática](https://raras.org/doenca/porfiria-hepatica) — ORPHA:659694 — 27 sintomas em comum

## Importante

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Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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