Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease

Meral Gunay-Aygun, Esperanza Font-Montgomery, Linda Lukose, Maya Tuchman Gerstein, Katie Piwnica-Worms, Peter Choyke, Kailash T. Daryanani, Baris Turkbey, Roxanne Fischer, Isa Bernardini, Murat Sincan, Xiongce Zhao, Netanya G. Sandler, Annelys Roque, Daniel C. Douek, Jennifer Graf, Marjan Huizing, Joy C. Bryant, Parvathi Mohan, William A. Gahl & 1 others Theo Heller

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Background & Aims: Autosomal recessive polycystic kidney disease (ARPKD), the most common ciliopathy of childhood, is characterized by congenital hepatic fibrosis and progressive cystic degeneration of kidneys. We aimed to describe congenital hepatic fibrosis in patients with ARPKD, confirmed by detection of mutations in PKHD1. Methods: Patients with ARPKD and congenital hepatic fibrosis were evaluated at the National Institutes of Health from 2003 to 2009. We analyzed clinical, molecular, and imaging data from 73 patients (age, 1-56 years; average, 12.7 ± 13.1 years) with kidney and liver involvement (based on clinical, imaging, or biopsy analyses) and mutations in PKHD1. Results: Initial symptoms were liver related in 26% of patients, and others presented with kidney disease. One patient underwent liver and kidney transplantation, and 10 others received kidney transplants. Four presented with cholangitis and one with variceal bleeding. Sixty-nine percent of patients had enlarged left lobes on magnetic resonance imaging, 92% had increased liver echogenicity on ultrasonography, and 65% had splenomegaly. Splenomegaly started early in life; 60% of children younger than 5 years had enlarged spleens. Spleen volume had an inverse correlation with platelet count and prothrombin time but not with serum albumin level. Platelet count was the best predictor of spleen volume (area under the curve of 0.88905), and spleen length corrected for patient's height correlated inversely with platelet count (R2 = 0.42, P <.0001). Spleen volume did not correlate with renal function or type of PKHD1 mutation. Twenty-two of 31 patients who underwent endoscopy were found to have varices. Five had variceal bleeding, and 2 had portosystemic shunts. Forty-percent had Caroli syndrome, and 30% had an isolated dilated common bile duct. Conclusions: Platelet count is the best predictor of the severity of portal hypertension, which has early onset but is underdiagnosed in patients with ARPKD. Seventy percent of patients with ARPKD have biliary abnormalities. Kidney and liver disease are independent, and variability in severity is not explainable by type of PKHD1 mutation; ClinicalTrials.gov number, NCT00068224.

Original languageEnglish (US)
JournalGastroenterology
Volume144
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Fingerprint

Autosomal Recessive Polycystic Kidney
Platelet Count
Splenomegaly
Spleen
Mutation
Kidney Diseases
Kidney
Liver
Caroli Disease
Congenital Hepatic Fibrosis
Hemorrhage
Surgical Portasystemic Shunt
Cystic Kidney Diseases
Molecular Imaging
Cholangitis
Prothrombin Time
National Institutes of Health (U.S.)
Varicose Veins
Common Bile Duct
Portal Hypertension

Keywords

  • Ductal Plate Malformation
  • Genetics
  • Hepatorenal Fibrocystic Disease
  • Noncirrhotic Portal Hypertension

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Gunay-Aygun, M., Font-Montgomery, E., Lukose, L., Tuchman Gerstein, M., Piwnica-Worms, K., Choyke, P., ... Heller, T. (2013). Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. Gastroenterology, 144(1). https://doi.org/10.1053/j.gastro.2012.09.056

Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. / Gunay-Aygun, Meral; Font-Montgomery, Esperanza; Lukose, Linda; Tuchman Gerstein, Maya; Piwnica-Worms, Katie; Choyke, Peter; Daryanani, Kailash T.; Turkbey, Baris; Fischer, Roxanne; Bernardini, Isa; Sincan, Murat; Zhao, Xiongce; Sandler, Netanya G.; Roque, Annelys; Douek, Daniel C.; Graf, Jennifer; Huizing, Marjan; Bryant, Joy C.; Mohan, Parvathi; Gahl, William A.; Heller, Theo.

In: Gastroenterology, Vol. 144, No. 1, 01.2013.

Research output: Contribution to journalArticle

Gunay-Aygun, M, Font-Montgomery, E, Lukose, L, Tuchman Gerstein, M, Piwnica-Worms, K, Choyke, P, Daryanani, KT, Turkbey, B, Fischer, R, Bernardini, I, Sincan, M, Zhao, X, Sandler, NG, Roque, A, Douek, DC, Graf, J, Huizing, M, Bryant, JC, Mohan, P, Gahl, WA & Heller, T 2013, 'Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease', Gastroenterology, vol. 144, no. 1. https://doi.org/10.1053/j.gastro.2012.09.056
Gunay-Aygun, Meral ; Font-Montgomery, Esperanza ; Lukose, Linda ; Tuchman Gerstein, Maya ; Piwnica-Worms, Katie ; Choyke, Peter ; Daryanani, Kailash T. ; Turkbey, Baris ; Fischer, Roxanne ; Bernardini, Isa ; Sincan, Murat ; Zhao, Xiongce ; Sandler, Netanya G. ; Roque, Annelys ; Douek, Daniel C. ; Graf, Jennifer ; Huizing, Marjan ; Bryant, Joy C. ; Mohan, Parvathi ; Gahl, William A. ; Heller, Theo. / Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. In: Gastroenterology. 2013 ; Vol. 144, No. 1.
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abstract = "Background & Aims: Autosomal recessive polycystic kidney disease (ARPKD), the most common ciliopathy of childhood, is characterized by congenital hepatic fibrosis and progressive cystic degeneration of kidneys. We aimed to describe congenital hepatic fibrosis in patients with ARPKD, confirmed by detection of mutations in PKHD1. Methods: Patients with ARPKD and congenital hepatic fibrosis were evaluated at the National Institutes of Health from 2003 to 2009. We analyzed clinical, molecular, and imaging data from 73 patients (age, 1-56 years; average, 12.7 ± 13.1 years) with kidney and liver involvement (based on clinical, imaging, or biopsy analyses) and mutations in PKHD1. Results: Initial symptoms were liver related in 26{\%} of patients, and others presented with kidney disease. One patient underwent liver and kidney transplantation, and 10 others received kidney transplants. Four presented with cholangitis and one with variceal bleeding. Sixty-nine percent of patients had enlarged left lobes on magnetic resonance imaging, 92{\%} had increased liver echogenicity on ultrasonography, and 65{\%} had splenomegaly. Splenomegaly started early in life; 60{\%} of children younger than 5 years had enlarged spleens. Spleen volume had an inverse correlation with platelet count and prothrombin time but not with serum albumin level. Platelet count was the best predictor of spleen volume (area under the curve of 0.88905), and spleen length corrected for patient's height correlated inversely with platelet count (R2 = 0.42, P <.0001). Spleen volume did not correlate with renal function or type of PKHD1 mutation. Twenty-two of 31 patients who underwent endoscopy were found to have varices. Five had variceal bleeding, and 2 had portosystemic shunts. Forty-percent had Caroli syndrome, and 30{\%} had an isolated dilated common bile duct. Conclusions: Platelet count is the best predictor of the severity of portal hypertension, which has early onset but is underdiagnosed in patients with ARPKD. Seventy percent of patients with ARPKD have biliary abnormalities. Kidney and liver disease are independent, and variability in severity is not explainable by type of PKHD1 mutation; ClinicalTrials.gov number, NCT00068224.",
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AU - Gunay-Aygun, Meral

AU - Font-Montgomery, Esperanza

AU - Lukose, Linda

AU - Tuchman Gerstein, Maya

AU - Piwnica-Worms, Katie

AU - Choyke, Peter

AU - Daryanani, Kailash T.

AU - Turkbey, Baris

AU - Fischer, Roxanne

AU - Bernardini, Isa

AU - Sincan, Murat

AU - Zhao, Xiongce

AU - Sandler, Netanya G.

AU - Roque, Annelys

AU - Douek, Daniel C.

AU - Graf, Jennifer

AU - Huizing, Marjan

AU - Bryant, Joy C.

AU - Mohan, Parvathi

AU - Gahl, William A.

AU - Heller, Theo

PY - 2013/1

Y1 - 2013/1

N2 - Background & Aims: Autosomal recessive polycystic kidney disease (ARPKD), the most common ciliopathy of childhood, is characterized by congenital hepatic fibrosis and progressive cystic degeneration of kidneys. We aimed to describe congenital hepatic fibrosis in patients with ARPKD, confirmed by detection of mutations in PKHD1. Methods: Patients with ARPKD and congenital hepatic fibrosis were evaluated at the National Institutes of Health from 2003 to 2009. We analyzed clinical, molecular, and imaging data from 73 patients (age, 1-56 years; average, 12.7 ± 13.1 years) with kidney and liver involvement (based on clinical, imaging, or biopsy analyses) and mutations in PKHD1. Results: Initial symptoms were liver related in 26% of patients, and others presented with kidney disease. One patient underwent liver and kidney transplantation, and 10 others received kidney transplants. Four presented with cholangitis and one with variceal bleeding. Sixty-nine percent of patients had enlarged left lobes on magnetic resonance imaging, 92% had increased liver echogenicity on ultrasonography, and 65% had splenomegaly. Splenomegaly started early in life; 60% of children younger than 5 years had enlarged spleens. Spleen volume had an inverse correlation with platelet count and prothrombin time but not with serum albumin level. Platelet count was the best predictor of spleen volume (area under the curve of 0.88905), and spleen length corrected for patient's height correlated inversely with platelet count (R2 = 0.42, P <.0001). Spleen volume did not correlate with renal function or type of PKHD1 mutation. Twenty-two of 31 patients who underwent endoscopy were found to have varices. Five had variceal bleeding, and 2 had portosystemic shunts. Forty-percent had Caroli syndrome, and 30% had an isolated dilated common bile duct. Conclusions: Platelet count is the best predictor of the severity of portal hypertension, which has early onset but is underdiagnosed in patients with ARPKD. Seventy percent of patients with ARPKD have biliary abnormalities. Kidney and liver disease are independent, and variability in severity is not explainable by type of PKHD1 mutation; ClinicalTrials.gov number, NCT00068224.

AB - Background & Aims: Autosomal recessive polycystic kidney disease (ARPKD), the most common ciliopathy of childhood, is characterized by congenital hepatic fibrosis and progressive cystic degeneration of kidneys. We aimed to describe congenital hepatic fibrosis in patients with ARPKD, confirmed by detection of mutations in PKHD1. Methods: Patients with ARPKD and congenital hepatic fibrosis were evaluated at the National Institutes of Health from 2003 to 2009. We analyzed clinical, molecular, and imaging data from 73 patients (age, 1-56 years; average, 12.7 ± 13.1 years) with kidney and liver involvement (based on clinical, imaging, or biopsy analyses) and mutations in PKHD1. Results: Initial symptoms were liver related in 26% of patients, and others presented with kidney disease. One patient underwent liver and kidney transplantation, and 10 others received kidney transplants. Four presented with cholangitis and one with variceal bleeding. Sixty-nine percent of patients had enlarged left lobes on magnetic resonance imaging, 92% had increased liver echogenicity on ultrasonography, and 65% had splenomegaly. Splenomegaly started early in life; 60% of children younger than 5 years had enlarged spleens. Spleen volume had an inverse correlation with platelet count and prothrombin time but not with serum albumin level. Platelet count was the best predictor of spleen volume (area under the curve of 0.88905), and spleen length corrected for patient's height correlated inversely with platelet count (R2 = 0.42, P <.0001). Spleen volume did not correlate with renal function or type of PKHD1 mutation. Twenty-two of 31 patients who underwent endoscopy were found to have varices. Five had variceal bleeding, and 2 had portosystemic shunts. Forty-percent had Caroli syndrome, and 30% had an isolated dilated common bile duct. Conclusions: Platelet count is the best predictor of the severity of portal hypertension, which has early onset but is underdiagnosed in patients with ARPKD. Seventy percent of patients with ARPKD have biliary abnormalities. Kidney and liver disease are independent, and variability in severity is not explainable by type of PKHD1 mutation; ClinicalTrials.gov number, NCT00068224.

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KW - Genetics

KW - Hepatorenal Fibrocystic Disease

KW - Noncirrhotic Portal Hypertension

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