Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis
Background & Aims: Polycystic liver disease (PLD) manifests as numerous fluid-filled cysts scattered throughout the liver parenchyma. PLD most commonly develops in females, either as an extra-renal manifestation of autosomal-dominant polycystic kidney disease (ADPKD) or as isolated autosomal...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555922001513 |
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| author | Dana Sierks Ria Schönauer Anja Friedrich Elena Hantmann Jonathan de Fallois Nikolas Linder Janett Fischer Adam Herber Carsten Bergmann Thomas Berg Jan Halbritter |
| author_facet | Dana Sierks Ria Schönauer Anja Friedrich Elena Hantmann Jonathan de Fallois Nikolas Linder Janett Fischer Adam Herber Carsten Bergmann Thomas Berg Jan Halbritter |
| author_sort | Dana Sierks |
| collection | DOAJ |
| description | Background & Aims: Polycystic liver disease (PLD) manifests as numerous fluid-filled cysts scattered throughout the liver parenchyma. PLD most commonly develops in females, either as an extra-renal manifestation of autosomal-dominant polycystic kidney disease (ADPKD) or as isolated autosomal-dominant polycystic liver disease (ADPLD). Despite known genetic causes, clinical variability challenges patient counselling and timely risk prediction is hampered by a lack of genotype-phenotype correlations and prognostic imaging classifications. Methods: We performed targeted next-generation sequencing and multiplex ligation-dependent probe amplification to identify the underlying genetic defect in a cohort of 80 deeply characterized patients with PLD. Identified genotypes were correlated with total liver and kidney volume (assessed by CT or MRI), organ function, co-morbidities, and clinical endpoints. Results: Monoallelic diagnostic variants were identified in 60 (75%) patients, 38 (48%) of which pertained to ADPKD-gene variants (PKD1, PKD2, GANAB) and 22 (27%) to ADPLD-gene variants (PRKCSH, SEC63). Disease severity defined by age at waitlisting for liver transplantation and first PLD-related hospitalization was significantly more pronounced in mutation carriers compared to patients without genetic diagnoses. While current imaging classifications proved unable to differentiate between severe and moderate courses, grouping by estimated age-adjusted total liver volume progression yielded significant risk discrimination. Conclusion: This study underlines the predictive value of providing a molecular diagnosis for patients with PLD. In addition, we propose a novel risk-classification model based on age- and height-adjusted total liver volume that could improve individual prognostication and personalized clinical management. Lay summary: Polycystic liver disease (PLD) is a highly variable condition that can be asymptomatic or severe. However, it is currently difficult to predict clinical outcomes such as hospitalization, symptom burden, and need for transplantation in individual patients. In the current study, we aimed to investigate the clinical value of genetic confirmation and an age-adjusted total liver volume classification for individual disease prediction. While genetic confirmation generally pointed to more severe disease, estimated age-adjusted increases in liver volume could be useful for predicting clinical outcomes. |
| first_indexed | 2024-04-12T11:45:27Z |
| format | Article |
| id | doaj.art-b8d51ffe40c4400a8346b121ecbd8216 |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-04-12T11:45:27Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-b8d51ffe40c4400a8346b121ecbd82162022-12-22T03:34:22ZengElsevierJHEP Reports2589-55592022-11-01411100579Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysisDana Sierks0Ria Schönauer1Anja Friedrich2Elena Hantmann3Jonathan de Fallois4Nikolas Linder5Janett Fischer6Adam Herber7Carsten Bergmann8Thomas Berg9Jan Halbritter10Division of Nephrology, Department of Internal Medicine, Leipzig University Medical Center, Leipzig, GermanyDivision of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Division of Nephrology, Department of Internal Medicine, Leipzig University Medical Center, Leipzig, GermanyMedizinische Genetik Mainz, Limbach Genetics, Mainz, GermanyDivision of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyDivision of Nephrology, Department of Internal Medicine, Leipzig University Medical Center, Leipzig, GermanyDepartment of Radiology, Leipzig University Medical Center, GermanyDivision of Hepatology, Department of Medicine II, Leipzig University Medical Center, GermanyDivision of Hepatology, Department of Medicine II, Leipzig University Medical Center, GermanyMedizinische Genetik Mainz, Limbach Genetics, Mainz, GermanyDivision of Hepatology, Department of Medicine II, Leipzig University Medical Center, Germany; Corresponding authors. Address: Division of Hepatology, Clinic for Oncology, Gastroenterology, Hepatology, Infectious Diseases and Pneumology, Leipzig University Medical Center, GermanyDivision of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Division of Nephrology, Department of Internal Medicine, Leipzig University Medical Center, Leipzig, Germany; Division of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin, Berlin, Germany.Background & Aims: Polycystic liver disease (PLD) manifests as numerous fluid-filled cysts scattered throughout the liver parenchyma. PLD most commonly develops in females, either as an extra-renal manifestation of autosomal-dominant polycystic kidney disease (ADPKD) or as isolated autosomal-dominant polycystic liver disease (ADPLD). Despite known genetic causes, clinical variability challenges patient counselling and timely risk prediction is hampered by a lack of genotype-phenotype correlations and prognostic imaging classifications. Methods: We performed targeted next-generation sequencing and multiplex ligation-dependent probe amplification to identify the underlying genetic defect in a cohort of 80 deeply characterized patients with PLD. Identified genotypes were correlated with total liver and kidney volume (assessed by CT or MRI), organ function, co-morbidities, and clinical endpoints. Results: Monoallelic diagnostic variants were identified in 60 (75%) patients, 38 (48%) of which pertained to ADPKD-gene variants (PKD1, PKD2, GANAB) and 22 (27%) to ADPLD-gene variants (PRKCSH, SEC63). Disease severity defined by age at waitlisting for liver transplantation and first PLD-related hospitalization was significantly more pronounced in mutation carriers compared to patients without genetic diagnoses. While current imaging classifications proved unable to differentiate between severe and moderate courses, grouping by estimated age-adjusted total liver volume progression yielded significant risk discrimination. Conclusion: This study underlines the predictive value of providing a molecular diagnosis for patients with PLD. In addition, we propose a novel risk-classification model based on age- and height-adjusted total liver volume that could improve individual prognostication and personalized clinical management. Lay summary: Polycystic liver disease (PLD) is a highly variable condition that can be asymptomatic or severe. However, it is currently difficult to predict clinical outcomes such as hospitalization, symptom burden, and need for transplantation in individual patients. In the current study, we aimed to investigate the clinical value of genetic confirmation and an age-adjusted total liver volume classification for individual disease prediction. While genetic confirmation generally pointed to more severe disease, estimated age-adjusted increases in liver volume could be useful for predicting clinical outcomes.http://www.sciencedirect.com/science/article/pii/S2589555922001513polycystic diseasepolycystic kidney diseaseADPLDADPKDPCLDPLD |
| spellingShingle | Dana Sierks Ria Schönauer Anja Friedrich Elena Hantmann Jonathan de Fallois Nikolas Linder Janett Fischer Adam Herber Carsten Bergmann Thomas Berg Jan Halbritter Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis JHEP Reports polycystic disease polycystic kidney disease ADPLD ADPKD PCLD PLD |
| title | Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis |
| title_full | Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis |
| title_fullStr | Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis |
| title_full_unstemmed | Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis |
| title_short | Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis |
| title_sort | modelling polycystic liver disease progression using age adjusted liver volumes and targeted mutational analysis |
| topic | polycystic disease polycystic kidney disease ADPLD ADPKD PCLD PLD |
| url | http://www.sciencedirect.com/science/article/pii/S2589555922001513 |
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