title: Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease.
abstract: OBJECTIVE
  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 (R(2) = 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.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland, USA. mgaygun@mail.nih.gov
authors.forename: Meral
authors.initials: M
authors.lastname: Gunay-Aygun
authors.forename: Esperanza
authors.initials: E
authors.lastname: Font-Montgomery
authors.forename: Linda
authors.initials: L
authors.lastname: Lukose
authors.forename: Maya
authors.initials: M
authors.lastname: Tuchman Gerstein
authors.forename: Katie
authors.initials: K
authors.lastname: Piwnica-Worms
authors.forename: Peter
authors.initials: P
authors.lastname: Choyke
authors.forename: Kailash T
authors.initials: KT
authors.lastname: Daryanani
authors.forename: Baris
authors.initials: B
authors.lastname: Turkbey
authors.forename: Roxanne
authors.initials: R
authors.lastname: Fischer
authors.forename: Isa
authors.initials: I
authors.lastname: Bernardini
authors.forename: Murat
authors.initials: M
authors.lastname: Sincan
authors.forename: Xiongce
authors.initials: X
authors.lastname: Zhao
authors.forename: Netanya G
authors.initials: NG
authors.lastname: Sandler
authors.forename: Annelys
authors.initials: A
authors.lastname: Roque
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Jennifer
authors.initials: J
authors.lastname: Graf
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.forename: Joy C
authors.initials: JC
authors.lastname: Bryant
authors.forename: Parvathi
authors.initials: P
authors.lastname: Mohan
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.forename: Theo
authors.initials: T
authors.lastname: Heller
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D002648:Child; D002675:Child, Preschool; D049448:Cholangiopancreatography, Magnetic Resonance; D016099:Endoscopy, Gastrointestinal; D004932:Esophageal and Gastric Varices / Q000209:etiology; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007223:Infant; D016030:Kidney Transplantation; D008103:Liver Cirrhosis / Q000151:congenital* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009929:Organ Size; D010976:Platelet Count; D017044:Polycystic Kidney, Autosomal Recessive / Q000150:complications / Q000235:genetics*; D017082:Portal Pressure; D011517:Prothrombin Time; D011956:Receptors, Cell Surface / Q000235:genetics*; D012709:Serum Albumin; D012720:Severity of Illness Index; D013163:Splenomegaly / Q000000981:diagnostic imaging; D018615:Ultrasonography, Doppler, Color; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface; D012709:Serum Albumin; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase