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Abstract: SA-PO744

Combined Consideration of Sex, Genotype, and Total Liver Volume Progression Determines the Risk of Hospitalization in an International Multicenter Cohort of Autosomal Dominant Polycystic Liver Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Sierks, Dana, Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany
  • Schönauer, Ria Anne-Rose, Division of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
  • Boerrigter, Melissa Maria, Division of Hepatology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
  • Jawaid, Tabinda, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Audrezet, Marie-Pierre, University of Brest, Inserm, CHU Brest, Brest, France
  • Caroff, Léa, University of Brest, Inserm, CHU Brest, Brest, France
  • Degenhardt, Jan Christoph, Department of Nephrology, University Hospital Cologne, Cologne, Germany
  • de Fallois, Jonathan, Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany
  • Schlevogt, Bernhard, Department of Medicine B, University Hospital Muenster, Muenster, Germany
  • Berg, Thomas, Division of Hepatology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany
  • Nevens, Frederik, University Hospitals KU, Leuven, Belgium
  • Watnick, Terry J., University of Maryland Medical System, Baltimore, Maryland, United States
  • Sayer, John Andrew, Translational and Clinical Medicine Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; NHS Foundation Trust, Newcastle upon Tyne Hospitals, Renal Services, Newcastle upon Tyne, UK; National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, United Kingdom
  • Besse, Whitney, Departments of Internal Medicine (Nephrology), Yale University School of Medicine, New Haven, Connecticut, United States
  • Cornec-Le Gall, Emilie, University of Brest, Inserm, CHU Brest, Brest, France
  • Harris, Peter C., Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Drenth, Joost Ph, Division of Hepatology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
  • Halbritter, Jan, Division of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Background

Autosomal dominant polycystic liver disease (ADPLD) is a rare disease with female preponderance, majorly based on pathogenic variants in PRKCSH or SEC63. Clinically, ADPLD is characterized by vast heterogeneity ranging from asymptomatic courses to highly symptomatic hepatomegaly. Little is known to predict disease progression at early stages hindering clinical management and genetic counselling. By establishing genotype-phenotype correlations, this study aims to improve disease prognostication in ADPLD.

Methods

We analyzed an international cohort from ten tertiary centers with 265 ADPLD patients harboring pathogenic variants in PRKCSH or SEC63. Genotypes were correlated with in-depth phenotypic data including normalized age-adjusted liver volume (nTLV) and PLD-related hospitalization (liver event).

Results

185 (70%) patients with ADPLD-PRKCSH and 80 (30%) patients with ADPLD-SEC63 were included (76% females). Classifying individual nTLV into predefined, age-adjusted progression groups yielded predictive risk discrimination for future liver events independent of sex and genetic defect (Fig. 1A). Additionally, severe disease in terms of onset of liver events was more likely in patients with PRKCSH variants as compared to those with SEC63 variants (Fig. 1B-C). A newly developed clinical score consisting of basic genotype and patient sex was able to discern mild courses from moderate and severe disease.

Conclusion

Both imaging and clinical genetic scoring have the potential to inform ADPLD-patients on their risk of developing symptomatic disease. Hereby, the combination of female sex, PRKCSH-disease, and rapid progression of hepatomegaly is associated with the greatest odds of PLD-related hospitalization.

Funding

  • Government Support – Non-U.S.