# Colestase intra-hepática familiar

> Página oficial: https://raras.org/doenca/colestase-intra-hepatica-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**: 284385 — https://www.orpha.net/en/disease/detail/284385
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Um caso de acúmulo de bile dentro do fígado, causado por uma alteração genética herdada no DNA da pessoa.

## Epidemiologia e herança


## Sinais e sintomas (111 fenótipos HPO)

- **Variz esofágica** — HPO: HP:0002040
- **Proteinúria** — HPO: HP:0000093
- **Colestase** — HPO: HP:0001396
- **Fibrose periportal** — HPO: HP:0001405
- **Fibrose intersticial renal** — HPO: HP:0032948
- **Hepatomegalia** — HPO: HP:0002240
- **Hidronefrose** — HPO: HP:0000126
- **Concentração anormal de bilirrubina circulante** — HPO: HP:0033479
- **Concentração elevada de alanina aminotransferase circulante** — HPO: HP:0031964
- **Trombose da veia porta** — HPO: HP:0030242
- **Hiperbilirrubinemia conjugada** — HPO: HP:0002908
- **Colestase intra-hepática com icterícia episódica** — HPO: HP:0006575
- **Desconforto respiratório** — HPO: HP:0002098
- **Prurido** — HPO: HP:0000989
- **Icterícia neonatal prolongada** — HPO: HP:0006579
- **Anemia** — HPO: HP:0001903
- **Hiperbilirrubinemia** — HPO: HP:0002904
- **Glomeruloesclerose segmentar focal** — HPO: HP:0000097
- **Cirrose micronodular** — HPO: HP:0001413
- **Sofrimento fetal** — HPO: HP:0025116
- **Cirrose biliar** — HPO: HP:0002613
- **Icterícia** — HPO: HP:0000952
- **Nível elevado de gama-glutamiltransferase** — HPO: HP:0030948
- **Icterícia intermitente** — HPO: HP:0001046
- **Neoplasia** — HPO: HP:0002664
- **Hipercolesterolemia** — HPO: HP:0003124
- **Tempo de coagulação do sangue total prolongado** — HPO: HP:0005542
- **Hepatoesplenomegalia** — HPO: HP:0001433
- **Hiperamonemia** — HPO: HP:0001987
- **Colestase intra-hepática** — HPO: HP:0001406
- **Insuficiência hepática** — HPO: HP:0001399
- **Déficit de crescimento** — HPO: HP:0001508
- **Diarreia** — HPO: HP:0002014
- **Rins hiperecogênicos** — HPO: HP:0004719
- **Lesão fibro-obliterativa do ducto biliar** — HPO: HP:0034328
- **Formato facial anormal** — HPO: HP:0001999
- **Esplenomegalia** — HPO: HP:0001744
- **Testes de função hepática anormais durante a gravidez** — HPO: HP:0200148
- **Má absorção de gordura** — HPO: HP:0002630
- **Anormalidade da coagulação** — HPO: HP:0001928
- _...e mais 71 sintomas. Ver https://raras.org/doenca/colestase-intra-hepatica-familiar._

## Genes associados (14)

- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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
- **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

## Medicamentos em desenvolvimento (3)

- ODEVIXIBAT SESQUIHYDRATE — Fase Phase 4 (Ileal bile acid transporter inhibitor)
- 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_0017290

## 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 — 107 sintomas em comum
- [Colestase intra-hepática progressiva familiar](https://raras.org/doenca/colestase-intra-hepatica-progressiva-familiar) — ORPHA:172 — 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 — 35 sintomas em comum
- [Colangite esclerosante](https://raras.org/doenca/colangite-esclerosante) — ORPHA:447771 — 35 sintomas em comum
- [Citrulinemia](https://raras.org/doenca/citrulinemia) — ORPHA:187 — 31 sintomas em comum
- [Deficiência de lipase ácida lisossomal](https://raras.org/doenca/deficiencia-de-lipase-acida-lisossomal) — ORPHA:275761 — 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
- [Porfiria hepática](https://raras.org/doenca/porfiria-hepatica) — ORPHA:659694 — 29 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

---

**Citação sugerida**: Raras.org — Colestase intra-hepática familiar. Disponível em: https://raras.org/doenca/colestase-intra-hepatica-familiar
**Formato HTML**: https://raras.org/doenca/colestase-intra-hepatica-familiar
**Formato RDF/Turtle**: https://raras.org/api/rdf?orpha=284385