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

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*

Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e318228330c
Original Articles: Hepatology and Nutrition

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 (, 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.

Author Information

*Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health

National Institutes of Health Clinical Center

Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD

§Children's National Medical Center, Washington, DC

||National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

Address correspondence and reprint requests to Meral Gunay-Aygun, MD, NHGRI, NIH, 10 Center Dr, Bldg 10, Rm 10C103, Bethesda, MD 20892 (e-mail:

Received 10 November, 2010

Accepted 7 February, 2011

This study was supported by the Intramural Research Program of the National Human Genome Research Institute and the NIH Clinical Center.

The authors report no conflicts of interest.

Copyright 2012 by ESPGHAN and NASPGHAN