Congenital Hepatic Fibrosis and Portal Hypertension in Autosomal Dominant Polycystic Kidney Disease

• Published in: Journal of pediatric gastroenterology and nutrition Vol. 54; no. 1; pp. 83 - 89
• Main Authors: O'Brien, Kevin, Font‐Montgomery, Esperanza, Lukose, Linda, Bryant, Joy, Piwnica‐Worms, Katie, Edwards, Hailey, Riney, Lauren, Garcia, Angelica, Daryanani, Kailash, Choyke, Peter, Mohan, Parvathi, Heller, Theo, Gahl, William A., Gunay‐Aygun, Meral
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Copyright by ESPGHAN and NASPGHAN 01.01.2012; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Aged; autosomal dominant polycystic kidney disease; autosomal recessive polycystic kidney disease; Biological and medical sciences; Child; Child, Preschool; Chromosomes; congenital hepatic fibrosis; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Genes, Modifier; Humans; Hypertension, Portal - etiology; Kidneys; Liver - enzymology; Liver - pathology; Liver - physiology; Liver Cirrhosis - congenital; Liver Cirrhosis - etiology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Malformations of the urinary system; Medical sciences; Middle Aged; Mutation; Nephrology. Urinary tract diseases; Other diseases. Semiology; Polycystic Kidney, Autosomal Dominant - complications; Polycystic Kidney, Autosomal Dominant - genetics; Polycystic Kidney, Autosomal Dominant - pathology; polycystic liver disease; portal hypertension; Receptors, Cell Surface - genetics; TRPP Cation Channels - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Young Adult; Hepatic fibrosis; Kidney disease; Urinary system disease; Portal circulation disease; Congenital; Polycystic kidney; Polycystic liver; Cardiovascular disease; Metabolic diseases; Hepatic disease; autosomal dominant polycystic kidney disease; polycystic liver disease; Genetic disease; Vascular disease; Cyst; Gastroenterology; Portal hypertension; Digestive diseases; autosomal recessive polycystic kidney disease; Benign neoplasm; congenital hepatic fibrosis
• ISSN: 0277-2116; 1536-4801
• DOI: 10.1097/MPG.0b013e318228330c

ABSTRACT Objectives: Autosomal dominant (ADPKD) and recessive (ARPKD) polycystic kidney diseases are the most common hepatorenal fibrocystic diseases (ciliopathies). Characteristics of liver disease of these disorders are quite different. All of the patients with ARPKD have congenital hepatic fibrosis (CHF) often complicated by portal hypertension. In contrast, typical liver involvement in ADPKD is polycystic liver disease, although rare atypical cases with CHF are reported. Our goal was to describe the characteristics of CHF in ADPKD. Patients and Methods: As a part of an intramural study of the National Institutes of Health on ciliopathies (www.clinicaltrials.gov, trial NCT00068224), we evaluated 8 patients from 3 ADPKD families with CHF. We present their clinical, biochemical, imaging, and PKD1 and PKHD1 sequencing results. In addition, we tabulate the characteristics of 15 previously reported patients with ADPKD‐CHF from 11 families. Results: In all of the 19 patients with ADPKD‐CHF (9 boys, 10 girls), portal hypertension was the main manifestation of CHF; hepatocelllular function was preserved and liver enzymes were largely normal. In all of the 14 families, CHF was not inherited vertically, that is the parents of the index cases had PKD but did not have CHF‐suggesting modifier gene(s). Our 3 families had pathogenic mutations in PKD1; sequencing of the PKHD1 gene as a potential modifier did not reveal any mutations. Conclusions: Characteristics of CHF in ADPKD are similar to CHF in ARPKD. ADPKD‐CHF is caused by PKD1 mutations, with probable contribution from modifying gene(s). Given that both boys and girls are affected, these modifier(s) are likely located on autosomal chromosome(s) and less likely X‐linked.