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Cholestasis, progressive familial intrahepatic, 9(PFIC9)

MedGen UID:
1809292
Concept ID:
C5676973
Disease or Syndrome
Synonym: PFIC9
 
Gene (location): ZFYVE19 (15q15.1)
 
Monarch Initiative: MONDO:0030800
OMIM®: 619849

Definition

Progressive familial intrahepatic cholestasis-9 (PFIC9) is an autosomal recessive disorder characterized by onset of cholestasis associated with increased serum gamma-glutamyltransferase (GGT) in infancy or early childhood. Affected individuals have hepatosplenomegaly and may have portal hypertension or upper gastrointestinal bleeding. Liver biopsy shows fibrosis, cirrhosis, bile duct proliferation, and abnormal bile duct morphology. The disorder is thought to result from ciliary defects in cholangiocytes, consistent with a ciliopathy that appears to be restricted to the liver. Treatment with ursodeoxycholic acid (UDCA) or liver transplant is effective (Luan et al., 2021). For a discussion of genetic heterogeneity of progressive familial intrahepatic cholestasis, see PFIC1 (211600). [from OMIM]

Clinical features

From HPO
Portal hypertension
MedGen UID:
9375
Concept ID:
C0020541
Disease or Syndrome
Increased pressure in the portal vein.
Intrahepatic cholestasis
MedGen UID:
3042
Concept ID:
C0008372
Disease or Syndrome
Impairment of bile flow due to obstruction in the small bile ducts within the liver.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Micronodular cirrhosis
MedGen UID:
75640
Concept ID:
C0267812
Disease or Syndrome
A type of cirrhosis characterized by the presence of small regenerative nodules.
Malformation of the hepatic ductal plate
MedGen UID:
346605
Concept ID:
C1857519
Finding
Fibro-obliterative bile-duct lesion
MedGen UID:
1815078
Concept ID:
C5706172
Anatomical Abnormality
A condition in which the lumen of a bile duct has been filled by fibrous scar material, in effect replacing the bile duct with a fibrous scar.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Pruritus
MedGen UID:
19534
Concept ID:
C0033774
Sign or Symptom
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.

Professional guidelines

PubMed

Varol Fİ, Selimoğlu MA, Güngör Ş, Yılmaz S, Tekedereli İ
Arab J Gastroenterol 2021 Dec;22(4):310-315. Epub 2021 Nov 25 doi: 10.1016/j.ajg.2021.05.021. PMID: 34840097
Chen HL, Li HY, Wu JF, Wu SH, Chen HL, Yang YH, Hsu YH, Liou BY, Chang MH, Ni YH
J Pediatr 2019 Feb;205:153-159.e6. Epub 2018 Oct 23 doi: 10.1016/j.jpeds.2018.09.028. PMID: 30366773
Kaliciński PJ, Ismail H, Jankowska I, Kamiński A, Pawłowska J, Drewniak T, Markiewicz M, Szymczak M
Eur J Pediatr Surg 2003 Oct;13(5):307-11. doi: 10.1055/s-2003-43570. PMID: 14618520

Recent clinical studies

Etiology

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
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
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
Varol Fİ, Selimoğlu MA, Güngör Ş, Yılmaz S, Tekedereli İ
Arab J Gastroenterol 2021 Dec;22(4):310-315. Epub 2021 Nov 25 doi: 10.1016/j.ajg.2021.05.021. PMID: 34840097
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

Diagnosis

Chen R, Yang FX, Tan YF, Deng M, Li H, Xu Y, Ouyang WX, Song YZ
Orphanet J Rare Dis 2022 Dec 22;17(1):445. doi: 10.1186/s13023-022-02597-y. PMID: 36550572Free 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
Varol Fİ, Selimoğlu MA, Güngör Ş, Yılmaz S, Tekedereli İ
Arab J Gastroenterol 2021 Dec;22(4):310-315. Epub 2021 Nov 25 doi: 10.1016/j.ajg.2021.05.021. PMID: 34840097
Baumann U, Sturm E, Lacaille F, Gonzalès E, Arnell H, Fischler B, Jørgensen MH, Thompson RJ, Mattsson JP, Ekelund M, Lindström E, Gillberg PG, Torfgård K, Soni PN
Clin Res Hepatol Gastroenterol 2021 Sep;45(5):101751. Epub 2021 Jun 26 doi: 10.1016/j.clinre.2021.101751. PMID: 34182185
Lipiński P, Ciara E, Jurkiewicz D, Płoski R, Wawrzynowicz-Syczewska M, Pawłowska J, Jankowska I
Ann Hepatol 2021 Nov-Dec;25:100342. Epub 2021 Mar 20 doi: 10.1016/j.aohep.2021.100342. PMID: 33757843

Therapy

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
Chen R, Yang FX, Tan YF, Deng M, Li H, Xu Y, Ouyang WX, Song YZ
Orphanet J Rare Dis 2022 Dec 22;17(1):445. doi: 10.1186/s13023-022-02597-y. PMID: 36550572Free 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
Loomes KM, Squires RH, Kelly D, Rajwal S, Soufi N, Lachaux A, Jankowska I, Mack C, Setchell KDR, Karthikeyan P, Kennedy C, Dorenbaum A, Desai NK, Garner W, Jaecklin T, Vig P, Miethke A, Thompson RJ
Hepatol Commun 2022 Sep;6(9):2379-2390. Epub 2022 May 4 doi: 10.1002/hep4.1980. PMID: 35507739Free PMC Article
Baumann U, Sturm E, Lacaille F, Gonzalès E, Arnell H, Fischler B, Jørgensen MH, Thompson RJ, Mattsson JP, Ekelund M, Lindström E, Gillberg PG, Torfgård K, Soni PN
Clin Res Hepatol Gastroenterol 2021 Sep;45(5):101751. Epub 2021 Jun 26 doi: 10.1016/j.clinre.2021.101751. PMID: 34182185

Prognosis

Kondou H, Nakano S, Mizuno T, Bessho K, Hasegawa Y, Nakazawa A, Tanikawa K, Azuma Y, Okamoto T, Inui A, Imagawa K, Kasahara M, Zen Y, Suzuki M, Hayashi H
Orphanet J Rare Dis 2024 Feb 10;19(1):57. doi: 10.1186/s13023-024-03080-6. PMID: 38341604Free PMC Article
Chen R, Yang FX, Tan YF, Deng M, Li H, Xu Y, Ouyang WX, Song YZ
Orphanet J Rare Dis 2022 Dec 22;17(1):445. doi: 10.1186/s13023-022-02597-y. PMID: 36550572Free PMC Article
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
Lipiński P, Ciara E, Jurkiewicz D, Płoski R, Wawrzynowicz-Syczewska M, Pawłowska J, Jankowska I
Ann Hepatol 2021 Nov-Dec;25:100342. Epub 2021 Mar 20 doi: 10.1016/j.aohep.2021.100342. PMID: 33757843
Hori T, Nguyen JH, Uemoto S
Hepatobiliary Pancreat Dis Int 2010 Dec;9(6):570-8. PMID: 21134824

Clinical prediction guides

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
Mighiu C, O'Hara S, Ferri Grazzi E, Murray KF, Schattenberg JM, Ventura E, Karakaidos M, Taylor A, Brrang H, Dhawan A, Willemse J, Finnegan A
Orphanet J Rare Dis 2022 Feb 2;17(1):32. doi: 10.1186/s13023-022-02177-0. PMID: 35109890Free PMC Article
Varol Fİ, Selimoğlu MA, Güngör Ş, Yılmaz S, Tekedereli İ
Arab J Gastroenterol 2021 Dec;22(4):310-315. Epub 2021 Nov 25 doi: 10.1016/j.ajg.2021.05.021. PMID: 34840097
Baumann U, Sturm E, Lacaille F, Gonzalès E, Arnell H, Fischler B, Jørgensen MH, Thompson RJ, Mattsson JP, Ekelund M, Lindström E, Gillberg PG, Torfgård K, Soni PN
Clin Res Hepatol Gastroenterol 2021 Sep;45(5):101751. Epub 2021 Jun 26 doi: 10.1016/j.clinre.2021.101751. PMID: 34182185
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

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

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