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Progressive familial intrahepatic cholestasis(PFIC)

MedGen UID:
75668
Concept ID:
C0268312
Disease or Syndrome
Synonyms: PFIC; Progressive family intrahepatic cholestasis; Progressive intrahepatic cholestasis
SNOMED CT: Progressive intrahepatic cholestasis (74162007); Familial intrahepatic cholestasis (74162007); Fatal intrahepatic cholestasis (74162007); Progressive familial intrahepatic cholestasis (74162007); PFIC - progressive familial intrahepatic cholestasis (74162007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Monarch Initiative: MONDO:0015762
OMIM® Phenotypic series: PS211600
Orphanet: ORPHA172

Definition

Progressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals.

Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3.

Signs and symptoms of PFIC typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly).

There are three known types of PFIC: PFIC1, PFIC2, and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause.

In addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis), and low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood. Affected individuals typically develop liver failure before adulthood.

The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Heinz N, Vittorio J
Curr Gastroenterol Rep 2023 Nov;25(11):344-354. Epub 2023 Aug 31 doi: 10.1007/s11894-023-00891-8. PMID: 37651067
Feldman AG, Sokol RJ
Semin Pediatr Surg 2020 Aug;29(4):150945. Epub 2020 Jul 23 doi: 10.1016/j.sempedsurg.2020.150945. PMID: 32861449Free PMC Article
Chen HL, Wu SH, Hsu SH, Liou BY, Chen HL, Chang MH
J Biomed Sci 2018 Oct 26;25(1):75. doi: 10.1186/s12929-018-0475-8. PMID: 30367658Free PMC Article

Recent clinical studies

Etiology

Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz Ö, Fischler B, Gonzalès E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Özen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P
Lancet Gastroenterol Hepatol 2022 Sep;7(9):830-842. Epub 2022 Jul 1 doi: 10.1016/S2468-1253(22)00093-0. PMID: 35780807
Jones-Hughes T, Campbell J, Crathorne L
Orphanet J Rare Dis 2021 Jun 3;16(1):255. doi: 10.1186/s13023-021-01884-4. PMID: 34082807Free PMC Article
Amirneni S, Haep N, Gad MA, Soto-Gutierrez A, Squires JE, Florentino RM
World J Gastroenterol 2020 Dec 21;26(47):7470-7484. doi: 10.3748/wjg.v26.i47.7470. PMID: 33384548Free PMC Article
Feldman AG, Sokol RJ
Semin Pediatr Surg 2020 Aug;29(4):150945. Epub 2020 Jul 23 doi: 10.1016/j.sempedsurg.2020.150945. PMID: 32861449Free PMC Article
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549

Diagnosis

Heinz N, Vittorio J
Curr Gastroenterol Rep 2023 Nov;25(11):344-354. Epub 2023 Aug 31 doi: 10.1007/s11894-023-00891-8. PMID: 37651067
Feldman AG, Sokol RJ
Semin Pediatr Surg 2020 Aug;29(4):150945. Epub 2020 Jul 23 doi: 10.1016/j.sempedsurg.2020.150945. PMID: 32861449Free PMC Article
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549
Bull LN, Thompson RJ
Clin Liver Dis 2018 Nov;22(4):657-669. Epub 2018 Aug 3 doi: 10.1016/j.cld.2018.06.003. PMID: 30266155
Schonfeld EA, Brown RS Jr
Clin Liver Dis 2017 Nov;21(4):673-686. Epub 2017 Jul 29 doi: 10.1016/j.cld.2017.06.001. PMID: 28987255

Therapy

Daley J, Halligan K, Howrie D, Salgado CM, Superdock A, Friehling E, Bailey KM
J Pediatr Hematol Oncol 2023 Jul 1;45(5):e621-e623. Epub 2023 Jan 12 doi: 10.1097/MPH.0000000000002623. PMID: 36728269Free PMC Article
Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz Ö, Fischler B, Gonzalès E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Özen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P
Lancet Gastroenterol Hepatol 2022 Sep;7(9):830-842. Epub 2022 Jul 1 doi: 10.1016/S2468-1253(22)00093-0. PMID: 35780807
Shirley M
Drugs 2022 Jan;82(1):71-76. doi: 10.1007/s40265-021-01649-0. PMID: 34813049Free PMC Article
Deeks ED
Drugs 2021 Oct;81(15):1781-1786. doi: 10.1007/s40265-021-01594-y. PMID: 34499340Free PMC Article
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549

Prognosis

Miethke AG, Moukarzel A, Porta G, Covarrubias Esquer J, Czubkowski P, Ordonez F, Mosca A, Aqul AA, Squires RH, Sokal E, D'Agostino D, Baumann U, D'Antiga L, Kasi N, Laborde N, Arikan C, Lin CH, Gilmour S, Mittal N, Chiou FK, Horslen SP, Huber WD, Jaecklin T, Nunes T, Lascau A, Longpre L, Mogul DB, Garner W, Vig P, Hupertz VF, Gonzalez-Peralta RP, Ekong U, Hartley J, Laverdure N, Ovchinsky N, Thompson RJ
Lancet Gastroenterol Hepatol 2024 Jul;9(7):620-631. Epub 2024 May 6 doi: 10.1016/S2468-1253(24)00080-3. PMID: 38723644
Jeyaraj R, Maher ER, Kelly D
Lancet Child Adolesc Health 2024 Jan;8(1):75-84. Epub 2023 Nov 22 doi: 10.1016/S2352-4642(23)00259-6. PMID: 38006895
Jones-Hughes T, Campbell J, Crathorne L
Orphanet J Rare Dis 2021 Jun 3;16(1):255. doi: 10.1186/s13023-021-01884-4. PMID: 34082807Free PMC Article
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549
Condat B, Zanditenas D, Barbu V, Hauuy MP, Parfait B, El Naggar A, Collot V, Bonnet J, Ngo Y, Maftouh A, Dugué L, Balian C, Charlier A, Blazquez M, Rosmorduc O
Dig Liver Dis 2013 Nov;45(11):915-9. Epub 2013 May 16 doi: 10.1016/j.dld.2013.04.002. PMID: 23684896

Clinical prediction guides

Miethke AG, Moukarzel A, Porta G, Covarrubias Esquer J, Czubkowski P, Ordonez F, Mosca A, Aqul AA, Squires RH, Sokal E, D'Agostino D, Baumann U, D'Antiga L, Kasi N, Laborde N, Arikan C, Lin CH, Gilmour S, Mittal N, Chiou FK, Horslen SP, Huber WD, Jaecklin T, Nunes T, Lascau A, Longpre L, Mogul DB, Garner W, Vig P, Hupertz VF, Gonzalez-Peralta RP, Ekong U, Hartley J, Laverdure N, Ovchinsky N, Thompson RJ
Lancet Gastroenterol Hepatol 2024 Jul;9(7):620-631. Epub 2024 May 6 doi: 10.1016/S2468-1253(24)00080-3. PMID: 38723644
Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz Ö, Fischler B, Gonzalès E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Özen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P
Lancet Gastroenterol Hepatol 2022 Sep;7(9):830-842. Epub 2022 Jul 1 doi: 10.1016/S2468-1253(22)00093-0. PMID: 35780807
Jones-Hughes T, Campbell J, Crathorne L
Orphanet J Rare Dis 2021 Jun 3;16(1):255. doi: 10.1186/s13023-021-01884-4. PMID: 34082807Free PMC Article
Hayashi H, Osaka S, Sakabe K, Fukami A, Kishimoto E, Aihara E, Sabu Y, Mizutani A, Kusuhara H, Naritaka N, Zhang W, Huppert SS, Sakabe M, Nakamura T, Hu YC, Mayhew C, Setchell K, Takebe T, Asai A
Stem Cell Reports 2021 Feb 9;16(2):309-323. Epub 2021 Jan 14 doi: 10.1016/j.stemcr.2020.12.008. PMID: 33450190Free PMC Article
Lee CS, Kimura A, Wu JF, Ni YH, Hsu HY, Chang MH, Nittono H, Chen HL
J Lipid Res 2017 Mar;58(3):607-614. Epub 2017 Jan 10 doi: 10.1194/jlr.P070425. PMID: 28073941Free PMC Article

Recent systematic reviews

Kavallar AM, Mayerhofer C, Aldrian D, Okamoto T, Müller T, Vogel GF
Hepatol Commun 2023 Oct 1;7(10) Epub 2023 Sep 27 doi: 10.1097/HC9.0000000000000286. PMID: 37756114Free PMC Article
Bolia R, Goel AD, Sharma V, Srivastava A
Expert Rev Gastroenterol Hepatol 2022 Feb;16(2):163-172. Epub 2022 Feb 15 doi: 10.1080/17474124.2022.2032660. PMID: 35051344
Jones-Hughes T, Campbell J, Crathorne L
Orphanet J Rare Dis 2021 Jun 3;16(1):255. doi: 10.1186/s13023-021-01884-4. PMID: 34082807Free PMC Article
Verkade HJ, Thompson RJ, Arnell H, Fischler B, Gillberg PG, Mattsson JP, Torfgård K, Lindström E
J Pediatr Gastroenterol Nutr 2020 Aug;71(2):176-183. doi: 10.1097/MPG.0000000000002789. PMID: 32433433
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549

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