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Chebib FT, Hanna C, Harris PC, Torres VE, Dahl NK. Autosomal Dominant Polycystic Kidney Disease: A Review. JAMA 2025:2831904. [PMID: 40126492 DOI: 10.1001/jama.2025.0310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/25/2025]
Abstract
Importance Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and is the most common inherited kidney disorder worldwide. ADPKD accounts for 5% to 10% of kidney failure in the US and Europe, and its prevalence in the US is 9.3 per 10 000 individuals. Observations ADPKD is typically diagnosed in individuals aged 27 to 42 years and is primarily caused by pathogenic variants in the PKD1 (78%) or PKD2 (15%) genes. Most persons with ADPKD have an affected parent, but de novo disease is suggested in 10% to 25% of families. More than 90% of patients older than 35 years have hepatic cysts, which may cause abdominal discomfort and occasionally require medical or surgical intervention. Hypertension affects 70% to 80% of patients with ADPKD, and approximately 9% to 14% develop intracranial aneurysms, which have a rupture rate of 0.57 per 1000 patient-years. Approximately 50% of individuals with ADPKD require kidney replacement therapy by 62 years of age. The severity of kidney disease can be quantified using the Mayo Imaging Classification (MIC), which stratifies patients based on total kidney volume adjusted for height and age and ranges from 1A to 1E. Patients with MIC 1C to MIC 1E have larger kidneys because of more rapid growth (6%-10% per year) compared with those with MIC 1A and 1B (1%-5% per year) and have earlier progression to kidney replacement therapy, which occurs at a mean age of 58.4 years for MIC 1C, 52.5 years for MIC 1D, and 43.4 years for MIC 1E. Optimal management of ADPKD includes systolic blood pressure lower than 120 mm Hg for most patients, but lower than 110/75 mm Hg for patients with MIC 1C to 1E who have an estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m2 and are younger than 50 years, dietary sodium restriction (<2000 mg/d), weight management, and adequate hydration (>2.5 L daily). The vasopressin type 2 receptor antagonist tolvaptan reduces the annual rate of eGFR decline by 0.98 to 1.27 mL/min/1.73 m2 and is indicated for patients with MIC 1C to 1E or an eGFR decline greater than 3 mL/min/1.73 m2 per year to slow disease progression and delay the onset of kidney failure. Conclusion ADPKD is the most common genetic kidney disease worldwide and is characterized by progressive development of kidney cysts. Patients typically have hypertension and liver cysts, and 9% to 14% develop intracranial aneurysms. First-line treatment includes blood pressure control, dietary and weight management, and adequate hydration. Tolvaptan reduces the rate of eGFR decline for those at high risk of rapid progression to kidney failure.
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Affiliation(s)
- Fouad T Chebib
- Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, Florida
| | - Christian Hanna
- Division of Pediatric Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota
| | - Peter C Harris
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota
| | - Vicente E Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota
| | - Neera K Dahl
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota
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Devuyst O, Ahn C, Barten TR, Brosnahan G, Cadnapaphornchai MA, Chapman AB, Cornec-Le Gall E, Drenth JP, Gansevoort RT, Harris PC, Harris T, Horie S, Liebau MC, Liew M, Mallett AJ, Mei C, Mekahli D, Odland D, Ong AC, Onuchic LF, P-C Pei Y, Perrone RD, Rangan GK, Rayner B, Torra R, Mustafa R, Torres VE. KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Kidney Int 2025; 107:S1-S239. [PMID: 39848759 DOI: 10.1016/j.kint.2024.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 07/17/2024] [Indexed: 01/25/2025]
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Wang P, Kline TL, Missert AD, Cook CJ, Callstrom MR, Chan A, Hartman RP, Kelm ZS, Korfiatis P. A Classification-Based Adaptive Segmentation Pipeline: Feasibility Study Using Polycystic Liver Disease and Metastases from Colorectal Cancer CT Images. JOURNAL OF IMAGING INFORMATICS IN MEDICINE 2024; 37:2186-2194. [PMID: 38587766 PMCID: PMC11522206 DOI: 10.1007/s10278-024-01072-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Revised: 02/29/2024] [Accepted: 03/01/2024] [Indexed: 04/09/2024]
Abstract
Automated segmentation tools often encounter accuracy and adaptability issues when applied to images of different pathology. The purpose of this study is to explore the feasibility of building a workflow to efficiently route images to specifically trained segmentation models. By implementing a deep learning classifier to automatically classify the images and route them to appropriate segmentation models, we hope that our workflow can segment the images with different pathology accurately. The data we used in this study are 350 CT images from patients affected by polycystic liver disease and 350 CT images from patients presenting with liver metastases from colorectal cancer. All images had the liver manually segmented by trained imaging analysts. Our proposed adaptive segmentation workflow achieved a statistically significant improvement for the task of total liver segmentation compared to the generic single-segmentation model (non-parametric Wilcoxon signed rank test, n = 100, p-value << 0.001). This approach is applicable in a wide range of scenarios and should prove useful in clinical implementations of segmentation pipelines.
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Affiliation(s)
- Peilong Wang
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | | | | | - Cole J Cook
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | | | - Alex Chan
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | | | - Zachary S Kelm
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Schönauer R, Sierks D, Boerrigter M, Jawaid T, Caroff L, Audrezet MP, Friedrich A, Shaw M, Degenhardt J, Forberger M, de Fallois J, Bläker H, Bergmann C, Gödiker J, Schindler P, Schlevogt B, Müller RU, Berg T, Patterson I, Griffiths WJ, Sayer JA, Popp B, Torres VE, Hogan MC, Somlo S, Watnick TJ, Nevens F, Besse W, Cornec-Le Gall E, Harris PC, Drenth JPH, Halbritter J. Sex, Genotype, and Liver Volume Progression as Risk of Hospitalization Determinants in Autosomal Dominant Polycystic Liver Disease. Gastroenterology 2024; 166:902-914. [PMID: 38101549 DOI: 10.1053/j.gastro.2023.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 12/04/2023] [Accepted: 12/10/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND & AIMS Autosomal dominant polycystic liver disease is a rare condition with a female preponderance, based mainly on pathogenic variants in 2 genes, PRKCSH and SEC63. Clinically, autosomal dominant polycystic liver disease is characterized by vast heterogeneity, ranging from asymptomatic to highly symptomatic hepatomegaly. To date, little is known about the prediction of disease progression at early stages, hindering clinical management, genetic counseling, and the design of randomized controlled trials. To improve disease prognostication, we built a consortium of European and US centers to recruit the largest cohort of patients with PRKCSH and SEC63 liver disease. METHODS We analyzed an international multicenter cohort of 265 patients with autosomal dominant polycystic liver disease harboring pathogenic variants in PRKCSH or SEC63 for genotype-phenotype correlations, including normalized age-adjusted total liver volumes and polycystic liver disease-related hospitalization (liver event) as primary clinical end points. RESULTS Classifying individual total liver volumes into predefined progression groups yielded predictive risk discrimination for future liver events independent of sex and underlying genetic defects. In addition, disease severity, defined by age at first liver event, was considerably more pronounced in female patients and patients with PRKCSH variants than in those with SEC63 variants. A newly developed sex-gene score was effective in distinguishing mild, moderate, and severe disease, in addition to imaging-based prognostication. CONCLUSIONS Both imaging and clinical genetic scoring have the potential to inform patients about the risk of developing symptomatic disease throughout their lives. The combination of female sex, germline PRKCSH alteration, and rapid total liver volume progression is associated with the greatest odds of polycystic liver disease-related hospitalization.
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Affiliation(s)
- Ria Schönauer
- Department 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, University of Leipzig Medical Center, Leipzig, Germany
| | - Dana Sierks
- Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany; Department of Pediatric Surgery, Universitätsklinikum Leipzig, Leipzig, Germany
| | - Melissa Boerrigter
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Tabinda Jawaid
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Lea Caroff
- University of Brest, Institut National de la Santé et de la Recherche Médicale, UMR 1078, Génétique, Génomique Fonctionnelle et Biotechnologies, Brest, France; Centre Hospitalier Universitaire Brest, Service de Néphrologie, Centre de Référence Maladies Rénales Héréditaires de l'Enfant et de l'Adulte, Brest, France
| | - Marie-Pierre Audrezet
- Centre Hospitalier Universitaire Brest, Service de Génétique Moléculaire, Brest, France
| | - Anja Friedrich
- Medizinische Genetik Mainz, Limbach Genetics, Mainz, Germany
| | - Melissa Shaw
- Departments of Internal Medicine and Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Jan Degenhardt
- Department 2 of Internal Medicine, University of Cologne, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Mirjam Forberger
- Department of Pathology, University of Leipzig Medical Center, Leipzig, Germany
| | - Jonathan de Fallois
- Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany
| | - Hendrik Bläker
- Department of Pathology, University of Leipzig Medical Center, Leipzig, Germany
| | | | - Juliana Gödiker
- Department of Internal Medicine B, University Hospital Münster, Münster, Germany
| | | | - Bernhard Schlevogt
- Department of Internal Medicine B, University Hospital Münster, Münster, Germany; Department of Gastroenterology, Medical Center Osnabrück, Osnabrück, Germany
| | - Roman-U Müller
- Department 2 of Internal Medicine, University of Cologne, Faculty of Medicine, University Hospital Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, University of Leipzig Medical Center, Leipzig, Germany
| | - Ilse Patterson
- Department of Radiology, Cambridge University Hospitals, Cambridge, United Kingdom
| | - William J Griffiths
- Department of Hepatology, Cambridge Liver Unit, Cambridge University Hospitals, Cambridge, United Kingdom
| | - John A Sayer
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Renal Services, Newcastle upon Tyne National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom; National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne, United Kingdom
| | - Bernt Popp
- Berlin Institute of Health at Charité, Universitätsmedizin Berlin, Center of Functional Genomics, Berlin, Germany
| | - Vicente E Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Marie C Hogan
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Stefan Somlo
- Departments of Internal Medicine and Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Terry J Watnick
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Frederik Nevens
- Department of Hepatology and Liver Transplantation Unit, University Hospitals Katholieke Universiteit Leuven, Leuven, Belgium
| | - Whitney Besse
- Departments of Internal Medicine and Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Emilie Cornec-Le Gall
- University of Brest, Institut National de la Santé et de la Recherche Médicale, UMR 1078, Génétique, Génomique Fonctionnelle et Biotechnologies, Brest, France; Centre Hospitalier Universitaire Brest, Service de Néphrologie, Centre de Référence Maladies Rénales Héréditaires de l'Enfant et de l'Adulte, Brest, France
| | - Peter C Harris
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - Jan Halbritter
- Department 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, University of Leipzig Medical Center, Leipzig, Germany.
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Mahboobipour AA, Ala M, Safdari Lord J, Yaghoobi A. Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of polycystic liver disease. Orphanet J Rare Dis 2024; 19:175. [PMID: 38671465 PMCID: PMC11055360 DOI: 10.1186/s13023-024-03187-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 04/17/2024] [Indexed: 04/28/2024] Open
Abstract
Polycystic liver disease (PLD) is a rare condition observed in three genetic diseases, including autosomal dominant polycystic liver disease (ADPLD), autosomal dominant polycystic kidney disease (ADPKD), and autosomal recessive polycystic kidney disease (ARPKD). PLD usually does not impair liver function, and advanced PLD becomes symptomatic when the enlarged liver compresses adjacent organs or increases intra-abdominal pressure. Currently, the diagnosis of PLD is mainly based on imaging, and genetic testing is not required except for complex cases. Besides, genetic testing may help predict patients' prognosis, classify patients for genetic intervention, and conduct early treatment. Although the underlying genetic causes and mechanisms are not fully understood, previous studies refer to primary ciliopathy or impaired ciliogenesis as the main culprit. Primarily, PLD occurs due to defective ciliogenesis and ineffective endoplasmic reticulum quality control. Specifically, loss of function mutations of genes that are directly involved in ciliogenesis, such as Pkd1, Pkd2, Pkhd1, and Dzip1l, can lead to both hepatic and renal cystogenesis in ADPKD and ARPKD. In addition, loss of function mutations of genes that are involved in endoplasmic reticulum quality control and protein folding, trafficking, and maturation, such as PRKCSH, Sec63, ALG8, ALG9, GANAB, and SEC61B, can impair the production and function of polycystin1 (PC1) and polycystin 2 (PC2) or facilitate their degradation and indirectly promote isolated hepatic cystogenesis or concurrent hepatic and renal cystogenesis. Recently, it was shown that mutations of LRP5, which impairs canonical Wnt signaling, can lead to hepatic cystogenesis. PLD is currently treated by somatostatin analogs, percutaneous intervention, surgical fenestration, resection, and liver transplantation. In addition, based on the underlying molecular mechanisms and signaling pathways, several investigational treatments have been used in preclinical studies, some of which have shown promising results. This review discusses the clinical manifestation, complications, prevalence, genetic basis, and treatment of PLD and explains the investigational methods of treatment and future research direction, which can be beneficial for researchers and clinicians interested in PLD.
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Affiliation(s)
- Amir Ali Mahboobipour
- Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Moein Ala
- Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Javad Safdari Lord
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Yaghoobi
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- School of Biological Science, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran
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Gittus M, Moore J, Ong ACM. Liver transplant recipients with polycystic liver disease have longer waiting times but better long-term clinical outcomes than those with liver disease due to other causes: A retrospective cross-sectional study. PLoS One 2024; 19:e0294717. [PMID: 38165905 PMCID: PMC10760649 DOI: 10.1371/journal.pone.0294717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 11/06/2023] [Indexed: 01/04/2024] Open
Abstract
INTRODUCTION Liver transplantation is the only curative option for patients with polycystic liver disease (PLD). In the United Kingdom, these patients are listed on the variant syndrome list due to their preserved liver function reflected in the United Kingdom End-stage Liver Disease (UKELD) score. The transplantation and survival rates for this patient group in the UK have not been previously reported. METHODS A retrospective cross-sectional analysis of patients receiving liver transplantation between 2010 and 2017 was performed using the NHS blood and transplantation database. This database contains the demographic, clinical parameters, indication for transplantation and follow-up of all patients in UK-based transplant centres. Basic statistics was performed using SPSS version 27. RESULTS 5412 recipients received elective liver allografts in the study period. 1.6% (100) of recipients had PLD as their primary indication for transplantation with 60 receiving liver only allografts and 40 receiving combined liver-kidney allografts. PLD patients had a >3-fold longer mean waiting time for transplantation compared to non-PLD patients, 508 days v 154 days respectively. PLD patients receiving combined liver-kidney allografts had a longer waiting time than those receiving a liver only allograft, 610 days v 438 days respectively. There were comparable patient survival rates for people with PLD and non-PLD primary indications at 30 days (94.0% vs 97.6%) and 1 year (92.0% vs 93.2%) but improved survival rates at 5 years (81.3% vs 76.5%). There were also comparable allograft survival rates for people with PLD and non-PLD primary indications at 30 days (93.9% vs 95.3%) and 1 year (91.9% vs 91.2%) but improved survival rates at 5 years (82.5% vs 77.3%). Transplant centre-level analysis identified variation in the proportion of liver transplantations for people with PLD as their primary listed indication. CONCLUSIONS Patients with PLD wait significantly longer for liver transplantation compared to other indications. However, transplanted PLD patients demonstrate better longer-term patient and liver allograft survival rates compared to transplanted non-PLD patients. The unexpected variation between individual UK centres transplanting for PLD deserves further study.
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Affiliation(s)
- Matt Gittus
- Academic Nephrology Unit, Division of Clinical Medicine, Faculty of Health, Sheffield Teaching Hospitals Trust, University of Sheffield and Sheffield Kidney Institute, Sheffield, United Kingdom
| | - Joanna Moore
- Liver Transplant Unit, Leeds Teaching Hospitals Trust, Leeds, United Kingdom
| | - Albert C. M. Ong
- Academic Nephrology Unit, Division of Clinical Medicine, Faculty of Health, Sheffield Teaching Hospitals Trust, University of Sheffield and Sheffield Kidney Institute, Sheffield, United Kingdom
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Quaglia A, Roberts EA, Torbenson M. Developmental and Inherited Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:122-294. [DOI: 10.1016/b978-0-7020-8228-3.00003-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Mutua I, Sakulen H. Isolated polycystic liver disease in a child. Int J Surg Case Rep 2023; 112:108950. [PMID: 37837666 PMCID: PMC10667741 DOI: 10.1016/j.ijscr.2023.108950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 10/07/2023] [Accepted: 10/08/2023] [Indexed: 10/16/2023] Open
Abstract
INTRODUCTION Polycystic liver disease (PCLD) is a genetic disorder characterized by the growth of >10 cysts in the liver. PCLD is associated with polycystic kidney disease (PKD) in 80-90%of cases (Kothadia et al., 2023 [1]). PCLD can occur in isolation though rarely in children. We present a case report of a child with symptomatic isolated PCLD. CASE PRESENTATION A 23-month old female child presented with a 17-month history of gradual increase in abdominal mass. She had acute onset of postprandial vomiting and shortness of breath while lying flat. On examination, she was irritable with massive abdominal distension. Liver function test done showed markedly elevated liver enzymes with preservation of liver synthesis function. Computed tomography (CT) scan showed a large intra-abdominal cyst and normal kidneys bilaterally. During laparotomy, we found multiple exophytic cysts arising from segment IVa of the liver. Hepatic resection was done successfully and patient recovered uneventfully. Histology showed Von Meyenburg complexes characteristic of PCLD. CLINICAL DISCUSSION The goal of management should be to counter symptomatology by intervening on developed cysts. The therapeutic options are individualized to address the symptoms and improve the patients' quality of life. Follow up of the patients is based on the presentation and intervention performed, during which period recurrence of cysts is assessed. Complete resection of the liver cysts is recommended to avoid the risk of cholangiocarcinoma. CONCLUSION Close follow up by physical examination, laboratory tests and imaging modalities is necessary to detect any recurring masses and malignancy transformation of the cysts to enable timely intervention.
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Affiliation(s)
- Irene Mutua
- Pediatric Surgeon, Kenyatta University Teaching Referral and Research Hospital, Kenya.
| | - Hargura Sakulen
- Hepatobiliary and Liver Transplant Surgeon, Kenyatta University Teaching Referral and Research Hospital, Kenya
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Smith SR, Matar AJ, Polireddy K, Feltracco HA, Sarmiento JM. Operative Outcomes for Polycystic Liver Disease: Results of a Large Contemporary Series. J Gastrointest Surg 2023; 27:2444-2450. [PMID: 37783909 DOI: 10.1007/s11605-023-05843-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 09/13/2023] [Indexed: 10/04/2023]
Abstract
INTRODUCTION Persistent symptoms of pain, early satiety, dyspnea, and gastrointestinal reflux due to significant liver enlargement are indications for surgical debulking in patients with polycystic liver disease (PCLD) due to the lack of effective medical therapies; however, few data exist on outcomes of surgical intervention for PCLD. METHODS We conducted a retrospective analysis of consecutive patients who underwent operative intervention due to persistent symptoms secondary to PCLD. Preoperative patient characteristics, 30-day postoperative outcomes, and long-term postoperative outcomes, including complications and symptom resolution, were analyzed. RESULTS We identified 50 patients who underwent hepatic resection for symptomatic PCLD. Nine patients (19%) had concomitant polycystic kidney disease, and 14 (28%) had previously undergone interventions for PCLD management. The overall complication rate was 30%, with 8 patients (16%) experiencing Clavien-Dindo Grade III-V complications and no mortalities. The median relative reduction in liver volume was 41%. At a median follow-up of 2 years, 94% has sustained symptom resolution. CONCLUSIONS This is among the largest case series exploring PCLD operative outcomes, revealing that surgical intervention for debulking for advanced PCLD is safe and effective for symptom management. Furthermore, patients with PCLD undergoing hepatectomy tolerate significant liver volume loss without evidence of impaired hepatic function.
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Affiliation(s)
- Savannah R Smith
- Department of Surgery, Emory University, 1364 Clifton Road NE, Suite H-100, Atlanta, GA, 30322, USA
| | - Abraham J Matar
- Department of Surgery, Emory University, 1364 Clifton Road NE, Suite H-100, Atlanta, GA, 30322, USA
| | - Karunesh Polireddy
- Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA
| | - Haley A Feltracco
- Department of Surgery, Emory University, 1364 Clifton Road NE, Suite H-100, Atlanta, GA, 30322, USA
| | - Juan M Sarmiento
- Department of Surgery, Emory University, 1364 Clifton Road NE, Suite H-100, Atlanta, GA, 30322, USA.
- Winship Cancer Institute, Emory University, 1365 Clifton Rd NE, Building A, Floor 4, Atlanta, GA, 30322, USA.
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11
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Billiet A, Temmerman F, Coudyzer W, Van den Ende N, Colle I, Francque S, De Maeght S, Janssens F, Orlent H, Sprengers D, Delwaide J, Decock S, De Vloo C, Moreno C, van Malenstein H, van der Merwe S, Verbeek J, Nevens F. Questionnaire PLD-complaint-specific assessment identifies need for therapy in polycystic liver disease: A multi-centric prospective study. United European Gastroenterol J 2023; 11:633-641. [PMID: 37278135 PMCID: PMC10493353 DOI: 10.1002/ueg2.12387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 03/01/2023] [Indexed: 06/07/2023] Open
Abstract
BACKGROUND AND AIMS Polycystic liver disease (PLD) can lead to extensive hepatomegaly. Symptom relief is the primary goal of the treatment. The role of the recently developed disease-specific questionnaires for identification of the thresholds and the assessment of therapy needs further investigation. METHODS A five-year prospective multi-centric observational study in 21 hospitals in Belgium gathered a study population of 198 symptomatic PLD-patients of whom the disease-specific symptom questionnaire PLD-complaint-specific assessment (POLCA) scores were calculated. The thresholds of the POLCA score for the need for volume reduction therapy were analyzed. RESULTS The study group consisted of mostly (82.8%) women with baseline mean age of 54.4 years ±11.2, median liver volume expressed as height-adjusted total liver volume(htLV) of 1994 mL (interquartile range [IQR] 1275; 3150) and median growth of the liver of +74 mL/year (IQR +3; +230). Volume reduction therapy was needed in 71 patients (35.9%). A POLCA severity score (SPI) ≥ 14 predicted the need for therapy both in the derivation (n = 63) and the validation cohort (n = 126). The thresholds to start somatostatin analogues (n = 55) or to consider liver transplantation (n = 18) were SPI scores of ≥14 and ≥ 18 and the corresponding mean htLVs were 2902 mL (IQR 1908; 3964) and 3607 mL (IQR 2901; 4337), respectively. Somatostatin analogues treatment resulted in a decrease in the SPI score -6.0 versus + 4.5 in patients without somatostatin analogues (p < 0.01). Changes in the SPI score were significantly different between the liver transplantation group and no liver transplantation group, +4.3 ± 7.1 versus -1.6 ± 4.9, respectively, (p < 0.01). CONCLUSION A polycystic liver disease-specific questionnaire can be used as a guide on when to start a volume reduction therapy and to assess the effect of treatment.
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Affiliation(s)
- Antoon Billiet
- Department of Gastroenterology and HepatologyUniversity Hospitals KU LeuvenEuropean Reference Network on liver disease (ERN Rare‐Liver)LeuvenBelgium
| | - Frederik Temmerman
- Department of Gastroenterology and HepatologyUniversity Hospitals KU LeuvenEuropean Reference Network on liver disease (ERN Rare‐Liver)LeuvenBelgium
| | - Walter Coudyzer
- Department of RadiologyUniversity Hospitals KU LeuvenLeuvenBelgium
| | - Natalie Van den Ende
- Department of Gastroenterology and HepatologyUniversity Hospitals KU LeuvenEuropean Reference Network on liver disease (ERN Rare‐Liver)LeuvenBelgium
| | - Isabelle Colle
- Department of Gastroenterology and HepatologyAlgemeen Stedelijk Ziekenhuis AalstAalstBelgium
| | - Sven Francque
- Department of Gastroenterology and HepatologyAntwerp University HospitalAntwerpBelgium
| | - Stephane De Maeght
- Department of Gastroenterology and HepatologyGrand Hôpital De Charleroi Saint‐JosephCharleroiBelgium
| | - Filip Janssens
- Department of Gastroenterology and HepatologyJessa ZiekenhuisHasseltBelgium
| | - Hans Orlent
- Department of Gastroenterology and HepatologyAZ Sint Jan BruggeBruggeBelgium
| | - Dirk Sprengers
- Department of Gastroenterology and HepatologyGZA AntwerpAntwerpenBelgium
| | - Jean Delwaide
- Department of Gastroenterology and HepatologyC.H.U. de LiègeLiègeBelgium
| | - Sofie Decock
- Department of Gastroenterology and HepatologyAZ Sint Lucas BruggeBruggeBelgium
| | - Charlotte De Vloo
- Department of Gastroenterology and HepatologyAZ DeltaRoeselareBelgium
| | - Christophe Moreno
- Department of Gastroenterology and HepatologyULB ErasmeBrusselsBelgium
| | - Hannah van Malenstein
- Department of Gastroenterology and HepatologyUniversity Hospitals KU LeuvenEuropean Reference Network on liver disease (ERN Rare‐Liver)LeuvenBelgium
| | - Schalk van der Merwe
- Department of Gastroenterology and HepatologyUniversity Hospitals KU LeuvenEuropean Reference Network on liver disease (ERN Rare‐Liver)LeuvenBelgium
| | - Jef Verbeek
- Department of Gastroenterology and HepatologyUniversity Hospitals KU LeuvenEuropean Reference Network on liver disease (ERN Rare‐Liver)LeuvenBelgium
| | - Frederik Nevens
- Department of Gastroenterology and HepatologyUniversity Hospitals KU LeuvenEuropean Reference Network on liver disease (ERN Rare‐Liver)LeuvenBelgium
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12
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Barten TRM, Staring CB, Hogan MC, Gevers TJG, Drenth JPH. Expanding the clinical application of the polycystic liver disease questionnaire: determination of a clinical threshold to select patients for therapy. HPB (Oxford) 2023; 25:890-897. [PMID: 37095030 DOI: 10.1016/j.hpb.2023.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 03/04/2023] [Accepted: 04/10/2023] [Indexed: 04/26/2023]
Abstract
BACKGROUND Polycystic liver disease (PLD) causes symptoms resulting from cystic volume expansion. The PLD-specific questionnaire (PLD-Q) captures symptom burden. This study aims to develop a threshold to identify patients with symptoms requiring further exploration and possibly intervention. METHODS We recruited PLD patients with completed PLD-Qs during their patient journey. We evaluated baseline PLD-Q scores in (un)treated PLD patients to determine a threshold of clinical importance. We assessed our threshold's discriminative ability with receiver operator characteristic statistics, Youden Index, sensitivity, specificity, positive and negative predictive value parameters. RESULTS We included 198 patients with a balanced proportion of treated (n=100) and untreated patients (n=98, PLD-Q scores 49 vs 19, p<0.001; median total liver volume 5827 vs 2185 ml, p<0.001). We established the PLD-Q threshold at 32 points. A score of ≥32 differentiates treated from untreated patients with an area under the ROC of 0.856, Youden Index 0.564, sensitivity of 85.0%, specificity of 71.4%, positive predictive value of 75.2%, and negative predictive value of 82.4%. Similar metrics were observed in predefined subgroups and an external cohort. CONCLUSION We established the PLD-Q threshold at 32 points with high discriminative ability to identify symptomatic patients. Patients with a score ≥32 should be eligible for treatment or inclusion in trials.
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Affiliation(s)
- Thijs R M Barten
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands; European Reference Network RARE-LIVER, Germany.
| | - Christian B Staring
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Marie C Hogan
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester MN, USA
| | - Tom J G Gevers
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands; European Reference Network RARE-LIVER, Germany; Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands; European Reference Network RARE-LIVER, Germany
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13
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Apple B, Sartori G, Moore B, Chintam K, Singh G, Anand PM, Strande NT, Mirshahi T, Triffo W, Chang AR. Individuals heterozygous for ALG8 protein-truncating variants are at increased risk of a mild cystic kidney disease. Kidney Int 2023; 103:607-615. [PMID: 36574950 PMCID: PMC10012037 DOI: 10.1016/j.kint.2022.11.025] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 11/10/2022] [Accepted: 11/23/2022] [Indexed: 12/25/2022]
Abstract
ALG8 protein-truncating variants (PTVs) have previously been described in patients with polycystic liver disease and in some cases cystic kidney disease. Given a lack of well-controlled studies, we determined whether individuals heterozygous for ALG8 PTVs are at increased risk of cystic kidney disease in a large, unselected health system-based observational cohort linked to electronic health records in Pennsylvania (Geisinger-Regeneron DiscovEHR MyCode study). Out of 174,172 patients, 236 were identified with ALG8 PTVs. Using ICD-based outcomes, patients with these variants were significantly at increased risk of having any kidney/liver cyst diagnosis (Odds Ratio 2.42, 95% confidence interval: 1.53-3.85), cystic kidney disease (3.03, 1.26-7.31), and nephrolithiasis (1.89, 1.96-2.97). To confirm this finding, blinded radiology review of computed tomography and magnetic resonance imaging studies was completed in a matched cohort of 52 thirty-plus year old ALG8 PTV heterozygotes and related non-heterozygotes. ALG8 PTV heterozygotes were significantly more likely to have cystic kidney disease, defined as four or more kidney cysts (57.7% vs. 7.7%), or bilateral kidney cysts (69.2% vs. 15.4%), but not one or more liver cyst (11.5% vs. 7.7%). In publicly available UK Biobank data, ALG8 PTV heterozygotes were at significantly increased risk of ICD code N28 (other disorders of kidney/ureter) (3.85% vs. 1.33%). ALG8 PTVs were not associated with chronic kidney disease or kidney failure in the MyCode study or the UK Biobank data. Thus, PTVs in ALG8 result in increased risk of a mild cystic kidney disease phenotype.
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Affiliation(s)
- Benjamin Apple
- Department of Medicine, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, USA
| | - Gino Sartori
- Department of Radiology, Geisinger, Danville, Pennsylvania, USA
| | - Bryn Moore
- Department of Genomic Health, Geisinger, Danville, Pennsylvania, USA
| | - Kiran Chintam
- Department of Nephrology, Geisinger, Danville, Pennsylvania, USA
| | - Gurmukteshwar Singh
- Department of Nephrology, Geisinger, Danville, Pennsylvania, USA; Center for Kidney Health Research, Department of Population Health Sciences, Geisinger, Danville, Pennsylvania, USA
| | - Prince Mohan Anand
- Department of Nephrology, Medical University of South Carolina, Lancaster, South Carolina, USA
| | - Natasha T Strande
- Department of Genomic Health, Geisinger, Danville, Pennsylvania, USA; Autism and Developmental Medicine Institute, Geisinger, Danville, Pennsylvania, USA
| | - Tooraj Mirshahi
- Department of Genomic Health, Geisinger, Danville, Pennsylvania, USA
| | - William Triffo
- Department of Radiology, Geisinger, Danville, Pennsylvania, USA
| | - Alexander R Chang
- Department of Nephrology, Geisinger, Danville, Pennsylvania, USA; Center for Kidney Health Research, Department of Population Health Sciences, Geisinger, Danville, Pennsylvania, USA.
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14
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Mirza H, Besse W, Somlo S, Weinreb J, Kenney B, Jain D. An update on ductal plate malformations and fibropolycystic diseases of the liver. Hum Pathol 2023; 132:102-113. [PMID: 35777701 DOI: 10.1016/j.humpath.2022.06.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 06/22/2022] [Indexed: 02/07/2023]
Abstract
A variety of cystic and fibrocystic lesions can occur in the liver, which may be single or multiple and etiologically can be acquired or have genetic underpinnings. Although the morphology of ductal plate development and various associated malformations has been well described, the genetic etiologies of many of these disorders are still poorly understood. Multiple clinical phenotypes in the liver are proposed to originate from ductal plate malformations: congenital hepatic fibrosis, Caroli's disease, Von Meyenburg complex, and the liver cysts of autosomal dominant polycystic kidney and liver diseases. Although many of the patients with these disorders, particularly with isolated liver involvement remain asymptomatic, some develop portal hypertension or symptoms from cyst enlargement. Development of hepatocellular malignancy is a risk in a small subset. Recent advances have made it now possible for some of these phenotypes to be genetically defined, and intriguingly animal models of adult polycystic liver disease suggest that abnormal organ development is not required. This review describes the current understanding, genetic underpinning, and key clinicopathologic and imaging features of these fibropolycystic liver diseases.
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Affiliation(s)
- Haris Mirza
- Department of Pathology, Yale School of Medicine, New Haven CT 06520, USA
| | - Whitney Besse
- Department of Internal Medicine (Section of Nephrology), Yale School of Medicine, New Haven CT 06520, USA
| | - Stefan Somlo
- Department of Internal Medicine (Section of Nephrology), Yale School of Medicine, New Haven CT 06520, USA; Department of Genetics, Yale School of Medicine, New Haven CT 06520, USA
| | - Jeffrey Weinreb
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven CT 06520, USA
| | - Barton Kenney
- Department of Pathology, Middlesex Health, Middletown CT 06457, USA
| | - Dhanpat Jain
- Department of Pathology, Yale School of Medicine, New Haven CT 06520, USA.
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15
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Drenth J, Barten T, Hartog H, Nevens F, Taubert R, Torra Balcells R, Vilgrain V, Böttler T. EASL Clinical Practice Guidelines on the management of cystic liver diseases. J Hepatol 2022; 77:1083-1108. [PMID: 35728731 DOI: 10.1016/j.jhep.2022.06.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 06/01/2022] [Indexed: 02/07/2023]
Abstract
The advent of enhanced radiological imaging techniques has facilitated the diagnosis of cystic liver lesions. Concomitantly, the evidence base supporting the management of these diseases has matured over the last decades. As a result, comprehensive clinical guidance on the subject matter is warranted. These Clinical Practice Guidelines cover the diagnosis and management of hepatic cysts, mucinous cystic neoplasms of the liver, biliary hamartomas, polycystic liver disease, Caroli disease, Caroli syndrome, biliary hamartomas and peribiliary cysts. On the basis of in-depth review of the relevant literature we provide recommendations to navigate clinical dilemmas followed by supporting text. The recommendations are graded according to the Oxford Centre for Evidence-Based Medicine system and categorised as 'weak' or 'strong'. We aim to provide the best available evidence to aid the clinical decision-making process in the management of patients with cystic liver disease.
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16
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Norcia LF, Watanabe EM, Hamamoto Filho PT, Hasimoto CN, Pelafsky L, de Oliveira WK, Sassaki LY. Polycystic Liver Disease: Pathophysiology, Diagnosis and Treatment. Hepat Med 2022; 14:135-161. [PMID: 36200122 PMCID: PMC9528914 DOI: 10.2147/hmer.s377530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 09/07/2022] [Indexed: 11/25/2022] Open
Abstract
Polycystic liver disease (PLD) is a clinical condition characterized by the presence of more than 10 cysts in the liver. It is a rare disease Of genetic etiology that presents as an isolated disease or assoc\iated with polycystic kidney disease. Ductal plate malformation, ciliary dysfunction, and changes in cell signaling are the main factors involved in its pathogenesis. Most patients with PLD are asymptomatic, but in 2-5% of cases the disease has disabling symptoms and a significant reduction in quality of life. The diagnosis is based on family history of hepatic and/or renal polycystic disease, clinical manifestations, patient age, and polycystic liver phenotype shown on imaging examinations. PLD treatment has evolved considerably in the last decades. Somatostatin analogues hold promise in controlling disease progression, but liver transplantation remains a unique curative treatment modality.
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Affiliation(s)
- Luiz Fernando Norcia
- Department of Surgery, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil
| | - Erika Mayumi Watanabe
- Department of Radiology, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil
| | - Pedro Tadao Hamamoto Filho
- Department of Neurology, Psychology and Psychiatry, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil
| | - Claudia Nishida Hasimoto
- Department of Surgery, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil
| | - Leonardo Pelafsky
- Department of Surgery, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil
| | - Walmar Kerche de Oliveira
- Department of Surgery, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil
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17
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Sierks D, Schönauer R, Friedrich A, Hantmann E, de Fallois J, Linder N, Fischer J, Herber A, Bergmann C, Berg T, Halbritter J. Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis. JHEP Rep 2022; 4:100579. [PMID: 36246085 PMCID: PMC9563211 DOI: 10.1016/j.jhepr.2022.100579] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 08/18/2022] [Accepted: 08/22/2022] [Indexed: 11/16/2022] Open
Affiliation(s)
- Dana Sierks
- Division of Nephrology, Department of Internal Medicine, Leipzig University Medical Center, Leipzig, Germany
| | - Ria Schönauer
- Division 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
| | - Anja Friedrich
- Medizinische Genetik Mainz, Limbach Genetics, Mainz, Germany
| | - Elena Hantmann
- Division of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Jonathan de Fallois
- Division of Nephrology, Department of Internal Medicine, Leipzig University Medical Center, Leipzig, Germany
| | - Nikolas Linder
- Department of Radiology, Leipzig University Medical Center, Germany
| | - Janett Fischer
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Germany
| | - Adam Herber
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Germany
| | | | - Thomas Berg
- Division 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, Germany
| | - Jan Halbritter
- Division 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.
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18
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Yoo JJ, Jo HI, Jung EA, Lee JS, Kim SG, Kim YS, Kim BK. Evidence of nonsurgical treatment for polycystic liver disease. Ther Adv Chronic Dis 2022; 13:20406223221112563. [PMID: 35898920 PMCID: PMC9310217 DOI: 10.1177/20406223221112563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Polycystic liver disease (PCLD) is the most common extrarenal manifestation of polycystic kidney disease. There is an urgent need to assess the efficacy and safety of nonsurgical modalities to relieve symptoms and decrease the severity of PCLD. Herein, we aimed to evaluate the efficacy of the nonsurgical treatment of PCLD and the quality of life of affected patients. METHODS PubMed, Ovid, MEDLINE, EMBASE, and the Cochrane Library were searched for studies on the nonsurgical modalities, either medications or radiological intervention to manage PCLD. Treatment efficacy, adverse events (AEs), and patient quality of life were evaluated. RESULTS In total, 27 studies involving 1037 patients were selected. After nonsurgical treatment, liver volume decreased by 259 ml/m [mean change (Δ) of 6.22%] and the effect was higher in the radiological intervention group [-1617 ml/m (-15.49%)] than in the medication group [-151 ml/m (-3.78%)]. The AEs and serious AEs rates after overall nonsurgical treatment were 0.50 [95% confidence interval (CI): 0.33-0.67] and 0.04 (95% CI: 0.01-0.07), respectively. The results of the SF-36 questionnaire showed that PCLD treatment improved physical function [physical component summary score of 4.18 (95% CI: 1.54-6.83)] but did not significantly improve mental function [mental component summary score of 0.91 (95% CI: -1.20 to 3.03)]. CONCLUSION Nonsurgical treatment was effective and safe for PCLD, but did not improve the quality of life in terms of mental health. Radiological intervention directly reduces hepatic cysts, and thus they should be considered for immediate symptom relief in patients with severe symptoms, whereas medication might be considered for maintenance treatment. REGISTRATION NUMBER PROSPERO (International Prospective Register of Systematic Reviews) CRD42021279597.
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Affiliation(s)
- Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang
University Bucheon Hospital, College of Medicine, Soonchunhyang University,
Bucheon, Republic of Korea
| | - Hye In Jo
- Department of Internal Medicine, Soonchunhyang
University Bucheon Hospital, College of Medicine, Soonchunhyang University,
Bucheon, Republic of Korea
| | - Eun-Ae Jung
- Medical Library, Soonchunhyang University
Bucheon Hospital, Bucheon, Republic of Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei
University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei
University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Cancer, Severance Hospital, Seoul,
Republic of Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang
University Bucheon Hospital, College of Medicine, Soonchunhyang University,
Bucheon, Republic of Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang
University Bucheon Hospital, College of Medicine, Soonchunhyang University,
Bucheon, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei
University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722,
Republic of Korea
- Institute of Gastroenterology, Yonsei
University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Cancer, Severance Hospital,
Seoul, Republic of Korea
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19
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Sharbidre K, Zahid M, Venkatesh SK, Bhati C, Lalwani N. Imaging of fibropolycystic liver disease. Abdom Radiol (NY) 2022; 47:2356-2370. [PMID: 35670875 DOI: 10.1007/s00261-022-03565-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 05/14/2022] [Accepted: 05/17/2022] [Indexed: 11/01/2022]
Abstract
Fibropolycystic liver diseases (FLDs) make up a rare spectrum of heritable hepatobiliary diseases resulting from congenital ductal plate malformations (DPMs) due to the dysfunction of proteins expressed on the primary cilia of cholangiocytes. The embryonic development of the ductal plate is key to understanding this spectrum of diseases. In particular, DPMs can result in various degrees of intrahepatic duct involvement and a wide spectrum of cholangiopathies, including congenital hepatic fibrosis, Caroli disease, polycystic liver disease, and Von Meyenberg complexes. The most common clinical manifestations of FLDs are portal hypertension, cholestasis, cholangitis, and (in rare cases) cholangiocarcinoma. This article reviews recent updates in the pathophysiology, imaging, and clinical management of FLDs.
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Affiliation(s)
- Kedar Sharbidre
- Department of Abdominal Imaging, University of Alabama at Birmingham, Birmingham, AB, USA.
| | - Mohd Zahid
- Department of Abdominal Imaging, University of Alabama at Birmingham, Birmingham, AB, USA
| | | | - Chandra Bhati
- Department of Transplant Surgery, University of Maryland Medical Center, Baltimore, ML, USA
| | - Neeraj Lalwani
- Department of Abdominal Imaging, Virginia Commonwealth University, Richmond, VA, USA
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20
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Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder that leads to chronic kidney disease and end-stage kidney disease (ESKD). Polycystic liver disease (PCLD) is the most common extrarenal manifestation of ADPKD. Though isolated PCLD and PCLD due to ADPKD are genetically distinct, they follow a similar clinical course of hepatomegaly from multiple cysts with preserved liver function. Tolvaptan use in ADPKD can slow down the deterioration of renal function and growth of cysts. Somatostatin analogs can slow the growth of polycystic livers but the effect is short-lived. The only curative therapy for PCLD is liver transplantation. Renal transplantation can significantly improve survival in patients with ESKD due to ADPKD.
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Affiliation(s)
- Rebecca Roediger
- Division of Liver Disease, Department of Medicine, Icahn School of Medicine, 1 Gustave L Levy Place, Box 1123, New York, NY 10029, USA.
| | - Douglas Dieterich
- Division of Liver Disease, Department of Medicine, Icahn School of Medicine, 1 Gustave L Levy Place, Box 1123, New York, NY 10029, USA
| | - Pramodh Chanumolu
- Division of Nephrology, Department of Medicine, Icahn School of Medicine, 1 Gustave L Levy Place, Box 1123, New York, NY 10029, USA
| | - Priya Deshpande
- Division of Nephrology, Department of Medicine, Icahn School of Medicine, 1 Gustave L Levy Place, Box 1123, New York, NY 10029, USA
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21
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Smith TW, Goldberg A, Lu AD. Preserving the organ donor pool and suprahepatic vena cava: Case series of transverse hepatectomy for polycystic liver disease. Ann Hepatol 2021; 20:100118. [PMID: 31543466 DOI: 10.1016/j.aohep.2019.06.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 05/10/2019] [Accepted: 06/23/2019] [Indexed: 02/04/2023]
Abstract
Management of symptomatic polycystic liver disease (PLD) has remained primarily unchanged since the early 20th century when multiple case reports described management of non-parasitic liver cysts. In 1968, Lin et al. described the fenestration procedure, "aspiration of the cysts, incision, partial excision with or without external drainage, or marsupilization and anastomosis to the gastrointestinal tract". Further surgical options have included cyst sclerotherapy, laparoscopic cyst aspiration, partial hepatectomy, and orthotopic liver transplant (OLT). Recently there has been discussion of medical management with somatostatin analogs to reduce hepatomegaly in PLD with varying success. There is no current consensus on treatment or standard of care for symptomatic PLD, it is largely up to surgeon preference and ability; however, there has been a movement toward early OLT with Model for End-Stage Liver Disease (MELD) score exception points. This case series reviews two female patients with normal renal and hepatic function with symptomatic PLD treated with transverse hepatectomy. We propose that patients suffering from symptomatic PLD, with retained renal and hepatic function, can be treated with transverse hepatectomy conserving limited donor livers for decompensated patients; moreover, transverse hepatectomy does not disrupt the major suprahepatic vena cava preserving potential surgical access for future OLT.
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Affiliation(s)
- Thomas W Smith
- Department of Surgery, Loyola University Medical Center, Maywood, IL, United States.
| | - Ari Goldberg
- Department of Radiology, Loyola University Medical Center, Maywood, IL, United States
| | - Amy D Lu
- Department of Surgery, Loyola University Medical Center, Maywood, IL, United States
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22
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Heterogeneous liver. Rev Med Interne 2021; 43:187-188. [PMID: 34563394 DOI: 10.1016/j.revmed.2021.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 08/28/2021] [Indexed: 11/22/2022]
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23
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Sureka B, Rastogi A, Bihari C, Bharathy KGS, Sood V, Alam S. Imaging in ductal plate malformations. Indian J Radiol Imaging 2021; 27:6-12. [PMID: 28515578 PMCID: PMC5385778 DOI: 10.4103/0971-3026.202966] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Ductal plate malformations are a heterogenous group of congenital fibrocystic liver diseases resulting from insult to the ductal plate at various stages of embryogenesis. As a result various biliary malformations, cysts, hamartomas and congenital hepatic fibrosis may be seen. We present a radiological pictorial of ductal plate malformations, accurate diagnosis of which is important for clinical management.
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Affiliation(s)
- Binit Sureka
- Department of Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kishore G S Bharathy
- Department of HPB Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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24
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Boillot O, Cayot B, Guillaud O, Crozet-Chaussin J, Hervieu V, Valette PJ, Dumortier J. Partial major hepatectomy with cyst fenestration for polycystic liver disease: Indications, short and long-term outcomes. Clin Res Hepatol Gastroenterol 2021; 45:101670. [PMID: 33722781 DOI: 10.1016/j.clinre.2021.101670] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/18/2021] [Accepted: 02/26/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVE Symptomatic polycystic liver disease (PLD) with massive hepatomegaly represents a challenging surgical issue. In this work, we focused on early and long term outcomes after partial hepatectomy with cyst fenestration (PHCF) in selected patients. METHODS All patients who had PHCF for treatment of PLD between January 2003 and December 2019 in our center were included in this study. PHCF was undertaken if at least one hepatic section was relatively spared from PLD, afferent and efferent hepatic vasculature was patent, and liver function was maintained. RESULTS Twenty nine patients (25 women) with a mean age of 54.6 ± 9 years underwent PHCF. Major hepatectomy was performed in all cases with 4.3 ± 0.8 resected segments. Overall perioperative morbidity (Clavien ≥ II) and mortality rates were 41.4.6% and 13.8% respectively. Significant postoperative liver volume reduction was 52.8% within the first year and 55.5% thereafter. From preoperative evaluation, performance status (PS) normalized or improved in 84% of patients. After a mean follow-up time of 70.8 ± 65 months, overall patient survival was 82.7%. In univariate analysis, PS, initial liver volume, operative time and transfusion were associated with post-operative complications and PS, preoperative cyst infection, portal hypertension, transfusion, postoperative sepsis and persistent ascites were associated with mortality. CONCLUSIONS Our study confirms that in spite of significant morbidity rate, PHCF allows a massive reduction of liver volume in selected patients with symptomatic PLD and is highly and durably effective for the reduction of liver volume and improvement of quality of life.
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Affiliation(s)
- Olivier Boillot
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Pavillon D, 69437 Lyon Cedex 03, France; Université Claude Bernard Lyon 1, France.
| | - Bénédicte Cayot
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Pavillon D, 69437 Lyon Cedex 03, France
| | - Olivier Guillaud
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Pavillon D, 69437 Lyon Cedex 03, France; Ramsay Générale de Santé, Clinique de la Sauvegarde, Lyon, France
| | - Jessica Crozet-Chaussin
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Pavillon D, 69437 Lyon Cedex 03, France
| | - Valérie Hervieu
- Service d'anatomopathologie, Hôpital Femme Mère Enfant, Bron, France
| | - Pierre-Jean Valette
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Pavillon D, 69437 Lyon Cedex 03, France; Université Claude Bernard Lyon 1, France
| | - Jérôme Dumortier
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Pavillon D, 69437 Lyon Cedex 03, France; Université Claude Bernard Lyon 1, France
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25
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Lee CH, Ahn C, Ryu H, Kang HS, Jeong SK, Jung KH. Clinical Factors Associated with the Risk of Intracranial Aneurysm Rupture in Autosomal Dominant Polycystic Kidney Disease. Cerebrovasc Dis 2021; 50:339-346. [PMID: 33706308 DOI: 10.1159/000513709] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 12/01/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The occurrence of intracranial aneurysms is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the healthy population. However, research concerning the factors related to the risk of intracranial aneurysm rupture in patients with ADPKD is still insufficient. OBJECTIVES The aim of the study was to investigate the prevalence of intracranial aneurysms and aneurysmal subarachnoid hemorrhage (SAH) and to analyze the systemic factors associated with high-risk aneurysms in patients with ADPKD. METHODS We screened patients who underwent cerebral angiography between January 2007 and May 2017 in the ADPKD registry. Patients were examined for the presence of intracranial aneurysms and subsequently reclassified into 3 groups based on the risk of aneurysmal rupture: the aneurysm-negative (group 1), low-risk aneurysm (group 2), or high-risk aneurysm (group 3). Various systemic factors were compared, and independent factors associated with high-risk aneurysms were analyzed. RESULTS Among the 926 patients, 148 (16.0%) had intracranial aneurysms and 11 (1.2%) had previous aneurysmal SAH. Patients with intracranial aneurysms were further classified into group 2 (low-risk aneurysms, 15.5%) or group 3 (high-risk aneurysms, 84.5%). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, p = 0.004), female sex (OR 3.13, 95% CI 1.94-5.0 6, p < 0.001), dolichoectasia (OR 8.57, 95% CI 1.53-48.17, p = 0.015), and mitral inflow deceleration time (DT) (OR 1.01, 95% CI 1.00-1.01, p = 0.046) were independently associated with high-risk aneurysms, whereas hypercholesterolemia (OR 0.46, 95% CI 0.29-0.72, p = 0.001) was negatively associated. CONCLUSION In the present study among patients with ADPKD, the prevalence of intracranial aneurysms and aneurysmal SAH was 16 and 1.2%, respectively. Age, female sex, dolichoectasia, and mitral inflow DT were positively associated with high-risk aneurysms, whereas hypercholesterolemia was negatively associated. A subsequent large-scaled longitudinal study is needed to define the plausibility of the clinical parameters.
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Affiliation(s)
- Chan-Hyuk Lee
- Department of Neurology, Jeonbuk National University Hospital and Medical School, Jeonju, Republic of Korea.,Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
| | - Curie Ahn
- Department of Nephrology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyunjin Ryu
- Department of Nephrology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyun-Seung Kang
- Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Seul-Ki Jeong
- Visual Intelligence Laboratory, Seul-Ki Jeong Neurology Clinic, Seoul, Republic of Korea
| | - Keun-Hwa Jung
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea,
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26
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Laparoscopic hepatic lobectomy for symptomatic polycystic liver disease. HPB (Oxford) 2021; 23:56-62. [PMID: 32451237 DOI: 10.1016/j.hpb.2020.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 04/15/2020] [Accepted: 04/20/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Laparoscopic fenestration has largely replaced open fenestration of liver cysts. However, most hepatectomies for polycystic liver disease (PCLD) are performed open. Outcomes data on laparoscopic hepatectomy for PCLD are lacking. METHODS Patients who underwent surgery for PCLD at a single institution between 2010 and 2019 were reviewed and grouped by operative approach. Pre- and post-operative volumes were calculated for patients who underwent resection. Primary outcomes were: volume reduction, re-admission and postoperative complications. RESULTS Twenty-six patients were treated for PCLD: 13 laparoscopic fenestration, nine laparoscopic hepatectomy, three open hepatectomy and one liver transplantation. Median length of stay for patients after laparoscopic resection was 3 days (IQR 2-3). The only complication was post-operative atrial fibrillation in one patient. There were no readmissions. Overall volume reduction was 51% (range 22-69) for all resections, 32% (range 22-46) after open resection and 56% (range 39-69) after laparoscopic resection. CONCLUSION Volume reduction achieved through laparoscopic approach exceeded open volume reduction at this institution and is comparable to volume reduction in previously published open resection series. Adequate volume reduction can be accomplished by laparoscopic means with acceptable postoperative morbidity.
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27
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Wang J, Yang H, Guo R, Sang X, Mao Y. Association of a novel PKHD1 mutation in a family with autosomal dominant polycystic liver disease. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:120. [PMID: 33569422 PMCID: PMC7867901 DOI: 10.21037/atm-20-3318] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Background Autosomal dominant polycystic liver disease (ADPLD) is characterized by multiple cysts in the liver without (or only occasional) renal cysts. At least seven genes are associated with high risk for developing ADPLD; however, clear genetic involvement is undetermined in more than 50% of ADPLD patients. Methods To identify additional ADPLD-associated genes, we collected 18 unrelated Chinese ADPLD cases, and performed whole exome sequencing on all the participants. After filtering the sequencing data against the human gene mutation database (HGMD) professional edition, we identified new mutations. We then sequenced this gene in family members of the patient. Results Among the 18 ADPLD cases analyzed by whole exome sequencing, we found 2 cases with a PRKCSH mutation (~11.1%), 2 cases with a PKD2 mutation (~11.1%), 1 case with both PKHD1 and PKD1 mutations (~5.6%), 1 case with GANAB mutation (~5.6%), 1 case with PKHD1 mutation (~5.6%), and 1 case with PKD1 mutations (~5.6%). We identified a new PKHD1 missense mutation in an ADPLD family, in which both patients showed innumerable small hepatic cysts, as reported previously. Additionally, we found that PRKCSH and SEC63 mutation frequencies were lower in the Chinese population compared with those in European and American populations. Conclusions We report a family with ADPLD associated with a novel PKHD1 mutation (G1210R). The genetic profile of ADPLD in the Chinese population is different from that in European and American populations, suggesting that further genetic research on genetic mutation of ADPLD in the Chinese population is warranted.
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Affiliation(s)
- Jiaru Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Huayu Yang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ruohan Guo
- Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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28
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Suwabe T, Chamberlain AM, Killian JM, King BF, Gregory AV, Madsen CD, Wang X, Kline TL, Chebib FT, Hogan MC, Kamath PS, Harris PC, Torres VE. Epidemiology of autosomal-dominant polycystic liver disease in Olmsted county. JHEP Rep 2020; 2:100166. [PMID: 33145487 PMCID: PMC7593615 DOI: 10.1016/j.jhepr.2020.100166] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 07/15/2020] [Accepted: 07/22/2020] [Indexed: 12/25/2022] Open
Abstract
Background & Aims Isolated autosomal-dominant polycystic liver disease (ADPLD) is generally considered a rare disease. However, the frequency of truncating mutations to ADPLD genes in large, population sequencing databases is 1:496. With the increasing use of abdominal imaging, incidental detection of hepatic cysts and ADPLD has become more frequent. The present study was performed to ascertain the incidence and point prevalence of ADPLD in Olmsted County, MN, USA, and how these are impacted by the increasing utilisation of abdominal imaging. Methods The Rochester Epidemiology Project and radiology databases of Mayo Clinic and Olmsted Medical Center were searched to identify all subjects meeting diagnostic criteria for definite, likely, or possible ADPLD. Annual incidence rates were calculated using incident cases during 1980–2016 as numerator, and age- and sex-specific estimates of the population of Olmsted County as denominator. Point prevalence was calculated using prevalence cases as numerator, and age- and sex-specific estimates of the population of Olmsted County on 1 January 2010 as denominator. Results The incidence rate and point prevalence of combined definite and likely ADPLD were 1.01 per 100,000 person-years and 9.5 per 100,000 population, respectively. Only 15 of 35 definite and likely incident ADPLD cases had received a diagnostic code, and only 8 had clinically significant hepatomegaly. The incidence rates were much higher when adding possible cases, mainly identified through radiology databases, particularly in recent years and in older patients because of the increased utilisation of imaging studies. Conclusions Clinically significant isolated ADPLD is a rare disease with a prevalence <1:10,000 population. The overall prevalence of ADPLD, however, to a large extent not clinically significant, is likely much higher and closer to the reported genetic prevalence. Lay summary Isolated autosomal-dominant polycystic liver disease (ADPLD) is generally considered a rare disease. However, we demonstrate that it is a relatively common disease, which is rarely (<1:10,000 population) clinically significant.
Isolated autosomal-dominant polycystic liver disease (ADPLD) is generally considered a rare disease. Truncating mutations to ADPLD genes are fairly common (1:496) in large, population sequencing databases. We identified 35 individuals meeting diagnostic criteria for definite or likely ADPLD and 99 additional patients with possible ADPLD. The point prevalence of definite or likely ADPLD on 01/01/2010 was 9.5/100,000 or 36.0/100,000 population if adding possible cases. Clinically significant isolated ADPLD is rare (<1:10,000 population), but the overall prevalence is likely much higher.
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Affiliation(s)
- Tatsuya Suwabe
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | | | - Jill M Killian
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Bernard F King
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Adriana V Gregory
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Charles D Madsen
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Xiaofang Wang
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | | | - Fouad T Chebib
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Marie C Hogan
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Peter C Harris
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Vicente E Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
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Wilson EM, Choi J, Torres VE, Somlo S, Besse W. Large Deletions in GANAB and SEC63 Explain 2 Cases of Polycystic Kidney and Liver Disease. Kidney Int Rep 2020; 5:727-731. [PMID: 32405593 PMCID: PMC7210741 DOI: 10.1016/j.ekir.2020.01.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/09/2020] [Accepted: 01/20/2020] [Indexed: 11/29/2022] Open
Affiliation(s)
- Elena M Wilson
- Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Jungmin Choi
- Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.,Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
| | - Vicente E Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
| | - Stefan Somlo
- Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, Connecticut, USA.,Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA
| | - Whitney Besse
- Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, Connecticut, USA
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30
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Li QQ, Guo XZ, Li HY, Qi XS. Portal hypertension in a patient with biliary hamartomas: A case report. World J Clin Cases 2020; 8:1745-1751. [PMID: 32420308 PMCID: PMC7211530 DOI: 10.12998/wjcc.v8.i9.1745] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/26/2020] [Accepted: 04/17/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Biliary hamartomas (BH) are a rare benign disease caused by malformation of the intrahepatic bile ducts. BH are occasionally diagnosed, but often lack obvious clinical symptoms. They are usually diagnosed by biopsy and imaging tests in clinical practice. Few studies have reported the association of BH with portal hypertension. CASE SUMMARY A 40-year-old man was repeatedly admitted to our hospital due to hematochezia. The source of bleeding was considered to be gastroesophageal varices and portal hypertensive gastropathy by endoscopy. He had no history of hepatitis virus infection, alcohol abuse, drug-induced liver injury, or autoimmune liver disease. He underwent magnetic resonance imaging, which showed rounded, irregular, low-signal-T1 and high-signal-T2 lesions diffusely distributed on the liver, that were not communicated with the biliary system on magnetic resonance cholangiopancreatography. According to the imaging examination, the patient was considered to have a diagnosis of BH with portal hypertension. CONCLUSION Based on the present case report, BH may be a potential etiology of portal hypertension.
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Affiliation(s)
- Qian-Qian Li
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
- Postgraduate College, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Xiao-Zhong Guo
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
| | - Hong-Yu Li
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
| | - Xing-Shun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
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31
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Zhang ZY, Wang ZM, Huang Y. Polycystic liver disease: Classification, diagnosis, treatment process, and clinical management. World J Hepatol 2020; 12:72-83. [PMID: 32231761 PMCID: PMC7097502 DOI: 10.4254/wjh.v12.i3.72] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 02/06/2020] [Accepted: 03/01/2020] [Indexed: 02/06/2023] Open
Abstract
Polycystic liver disease (PLD) is a rare hereditary disease that independently exists in isolated PLD, or as an accompanying symptom of autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease with complicated mechanisms. PLD currently lacks a unified diagnostic standard. The diagnosis of PLD is usually made when the number of hepatic cysts is more than 20. Gigot classification and Schnelldorfer classification are now commonly used to define severity in PLD. Most PLD patients have no clinical symptoms, and minority with severe complications need treatments. Somatostatin analogues, mammalian target of rapamycin inhibitor, ursodeoxycholic acid and vasopressin-2 receptor antagonist are the potentially effective medical therapies, while cyst aspiration and sclerosis, transcatheter arterial embolization, fenestration, hepatic resection and liver transplantation are the options of invasion therapies. However, the effectiveness of these therapies except liver transplantation are still uncertain. Furthermore, there is no unified strategy to treat PLD between medical centers at present. In order to better understand recent study progresses on PLD for clinical practice and obtain potential directions for future researches, this review mainly focuses on the recent progress in PLD classification, clinical manifestation, diagnosis and treatment. For information, we also provided medical treatment processes of PLD in our medical center.
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Affiliation(s)
- Ze-Yu Zhang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha 410000, Hunan Province, China
| | - Zhi-Ming Wang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha 410000, Hunan Province, China
| | - Yun Huang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha 410000, Hunan Province, China
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Matsubara T, Kozaka K, Matsui O, Nakanuma Y, Uesaka K, Inoue D, Yoneda N, Yoshida K, Kitao A, Yokka A, Koda W, Gabata T, Kobayashi S. Peribiliary glands: development, dysfunction, related conditions and imaging findings. Abdom Radiol (NY) 2020; 45:416-436. [PMID: 31707436 DOI: 10.1007/s00261-019-02298-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Peribiliary glands are minute structures that are distributed along the intrahepatic large bile ducts, extrahepatic bile duct, and cystic duct. These glands regulate many physiological functions, such as enzyme secretion. Pancreatic exocrine tissues and enzymes are often observed in peribiliary glands; thus, peribiliary glands are involved in enzyme secretion. As such, these glands can be affected by conditions such as IgG4-related sclerosing cholangitis based on commonalities with their pancreatic counterparts. Cystic changes in peribiliary glands can occur de novo, as part of a congenital syndrome, or secondary to insults such as alcoholic cirrhosis. Biliary tree stem/progenitor cells have recently been identified in peribiliary glands. These cells are involved in turnover and regeneration of biliary epithelia as well as in sclerosing reactions in some pathological conditions, such as primary sclerosing cholangitis and hepatolithiasis. Notably, hepatolithiasis is involved in mucin secretion by the peribiliary glands. Additionally, these cells are associated with the manifestation of several neoplasms, including intraductal papillary neoplasm, cystic micropapillary neoplasm, and cholangiocarcinoma. Normal peribiliary glands themselves are particularly small structures that cannot be recognized using any available imaging modalities; however, these glands are closely associated with several diseases, as mentioned above, which have typical imaging features. Therefore, knowledge of the basic pathophysiology of peribiliary glands is helpful for understanding biliary diseases associated with the peribiliary glands.
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Besse W, Chang AR, Luo JZ, Triffo WJ, Moore BS, Gulati A, Hartzel DN, Mane S, Torres VE, Somlo S, Mirshahi T. ALG9 Mutation Carriers Develop Kidney and Liver Cysts. J Am Soc Nephrol 2019; 30:2091-2102. [PMID: 31395617 DOI: 10.1681/asn.2019030298] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 06/26/2019] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND Mutations in PKD1 or PKD2 cause typical autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic kidney disease. Dominantly inherited polycystic kidney and liver diseases on the ADPKD spectrum are also caused by mutations in at least six other genes required for protein biogenesis in the endoplasmic reticulum, the loss of which results in defective production of the PKD1 gene product, the membrane protein polycystin-1 (PC1). METHODS We used whole-exome sequencing in a cohort of 122 patients with genetically unresolved clinical diagnosis of ADPKD or polycystic liver disease to identify a candidate gene, ALG9, and in vitro cell-based assays of PC1 protein maturation to functionally validate it. For further validation, we identified carriers of ALG9 loss-of-function mutations and noncarrier matched controls in a large exome-sequenced population-based cohort and evaluated the occurrence of polycystic phenotypes in both groups. RESULTS Two patients in the clinically defined cohort had rare loss-of-function variants in ALG9, which encodes a protein required for addition of specific mannose molecules to the assembling N-glycan precursors in the endoplasmic reticulum lumen. In vitro assays showed that inactivation of Alg9 results in impaired maturation and defective glycosylation of PC1. Seven of the eight (88%) cases selected from the population-based cohort based on ALG9 mutation carrier state who had abdominal imaging after age 50; seven (88%) had at least four kidney cysts, compared with none in matched controls without ALG9 mutations. CONCLUSIONS ALG9 is a novel disease gene in the genetically heterogeneous ADPKD spectrum. This study supports the utility of phenotype characterization in genetically-defined cohorts to validate novel disease genes, and provide much-needed genotype-phenotype correlations.
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Affiliation(s)
| | | | | | | | | | | | - Dustin N Hartzel
- Biomedical and Translational Informatics, Geisinger Clinic, Danville, Pennsylvania; and
| | - Shrikant Mane
- Genetics, Yale University School of Medicine, New Haven, Connecticut
| | | | - Vicente E Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Stefan Somlo
- Departments of Internal Medicine (Nephrology) and .,Genetics, Yale University School of Medicine, New Haven, Connecticut
| | - Tooraj Mirshahi
- Biomedical and Translational Informatics, Geisinger Clinic, Danville, Pennsylvania; and
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Bezençon J, Beaudoin JJ, Ito K, Fu D, Roth SE, Brock WJ, Brouwer KLR. Altered Expression and Function of Hepatic Transporters in a Rodent Model of Polycystic Kidney Disease. Drug Metab Dispos 2019; 47:899-906. [PMID: 31160314 PMCID: PMC6657211 DOI: 10.1124/dmd.119.086785] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 05/30/2019] [Indexed: 12/18/2022] Open
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a common form of inherited polycystic kidney disease (PKD) and is a leading cause of kidney failure. Fluid-filled cysts develop in the kidneys of patients with ADPKD, and cysts often form in their liver and other organs. Previous data have shown that bile acids are increased in the liver of polycystic kidney (PCK) rats, a rodent model of PKD; these changes may be associated with alterations in liver transporter expression and function. However, the impact of PKD on hepatic transporters has not been characterized. Therefore, this preclinical study was designed to investigate hepatic transporter expression and function in PCK compared with wild-type (WT) Sprague-Dawley rats. Transporter gene expression was measured by quantitative polymerase chain reaction, and protein levels were quantified by Western blot and liquid chromatography-tandem mass spectroscopy (LC-MS/MS)-based proteomic analysis in rat livers. Transporter function was assessed in isolated perfused livers (IPLs), and biliary and hepatic total glutathione content was measured. Protein expression of Mrp2 and Oatp1a4 was decreased 3.0-fold and 2.9-fold, respectively, in PCK rat livers based on Western blot analysis. Proteomic analysis confirmed a decrease in Mrp2 and a decrease in Oatp1a1 expression (PCK/WT ratios, 0.368 ± 0.098 and 0.563 ± 0.038, respectively; mean ± S.D.). The biliary excretion of 5(6)-carboxy-2',7'-dichlorofluorescein, a substrate of Oatp1a1, Mrp2, and Mrp3, was decreased 28-fold in PCK compared with WT rat IPLs. Total glutathione was significantly reduced in the bile of PCK rats. Differences in hepatic transporter expression and function may contribute to altered disposition of Mrp2 and Oatp substrates in PKD.
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Affiliation(s)
- Jacqueline Bezençon
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (J.B., J.J.B., K.I., D.F., K.L.R.B.); DMPK Research Department, Teijin Pharma Limited, Hino, Tokyo, Japan (K.I.); Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland (S.E.R.); and Brock Scientific Consulting, Montgomery Village, Maryland (W.J.B.)
| | - James J Beaudoin
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (J.B., J.J.B., K.I., D.F., K.L.R.B.); DMPK Research Department, Teijin Pharma Limited, Hino, Tokyo, Japan (K.I.); Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland (S.E.R.); and Brock Scientific Consulting, Montgomery Village, Maryland (W.J.B.)
| | - Katsuaki Ito
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (J.B., J.J.B., K.I., D.F., K.L.R.B.); DMPK Research Department, Teijin Pharma Limited, Hino, Tokyo, Japan (K.I.); Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland (S.E.R.); and Brock Scientific Consulting, Montgomery Village, Maryland (W.J.B.)
| | - Dong Fu
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (J.B., J.J.B., K.I., D.F., K.L.R.B.); DMPK Research Department, Teijin Pharma Limited, Hino, Tokyo, Japan (K.I.); Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland (S.E.R.); and Brock Scientific Consulting, Montgomery Village, Maryland (W.J.B.)
| | - Sharin E Roth
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (J.B., J.J.B., K.I., D.F., K.L.R.B.); DMPK Research Department, Teijin Pharma Limited, Hino, Tokyo, Japan (K.I.); Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland (S.E.R.); and Brock Scientific Consulting, Montgomery Village, Maryland (W.J.B.)
| | - William J Brock
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (J.B., J.J.B., K.I., D.F., K.L.R.B.); DMPK Research Department, Teijin Pharma Limited, Hino, Tokyo, Japan (K.I.); Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland (S.E.R.); and Brock Scientific Consulting, Montgomery Village, Maryland (W.J.B.)
| | - Kim L R Brouwer
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (J.B., J.J.B., K.I., D.F., K.L.R.B.); DMPK Research Department, Teijin Pharma Limited, Hino, Tokyo, Japan (K.I.); Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland (S.E.R.); and Brock Scientific Consulting, Montgomery Village, Maryland (W.J.B.)
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Zhang W, Blumenfeld JD, Prince MR. MRI in autosomal dominant polycystic kidney disease. J Magn Reson Imaging 2019; 50:41-51. [PMID: 30637853 DOI: 10.1002/jmri.26627] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 12/05/2018] [Accepted: 12/08/2018] [Indexed: 12/15/2022] Open
Abstract
Magnetic resonance imaging (MRI) is increasingly used in autosomal dominant polycystic kidney disease (ADPKD) for diagnosis, classification, assessment of disease progression and treatment response, and for identifying complications. Herein we review the role of MRI in the management of patients with ADPKD. We show how MRI-derived total kidney volume is a biomarker for assessing ADPKD severity and predicting decline in renal function. We also demonstrate the MR appearances of common complications. Level of Evidence: 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:41-51.
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Affiliation(s)
- Weiguo Zhang
- Department of Radiology, Weill Cornell Medicine, New York, New York, USA
| | - Jon D Blumenfeld
- Rogosin Institute, and Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Martin R Prince
- Department of Radiology, Weill Cornell Medicine, New York, New York, USA
- Columbia College of Physicians and Surgeons, New York, New York, USA
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Martin WP, Vaughan LE, Yoshida K, Takahashi N, Edwards ME, Metzger A, Senum SR, Masyuk TV, LaRusso NF, Griffin MD, El-Zoghby Z, Harris PC, Kremers WK, Nagorney DM, Kamath PS, Torres VE, Hogan MC. Bacterial Cholangitis in Autosomal Dominant Polycystic Kidney and Liver Disease. Mayo Clin Proc Innov Qual Outcomes 2019; 3:149-159. [PMID: 31193902 PMCID: PMC6543502 DOI: 10.1016/j.mayocpiqo.2019.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 03/12/2019] [Accepted: 03/20/2019] [Indexed: 12/24/2022] Open
Abstract
Objective To describe first episodes of bacterial cholangitis complicating autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD) and to identify risk factors for cholangitis episodes among patients with ADPKD-associated polycystic liver disease (PLD). Patients and Methods We searched the electronic medical records at our tertiary referral center for episodes of cholangitis in patients with ADPKD or ADPLD from January 1, 1996, through June 30, 2017. Cases were categorized as suspected or definite cholangitis by expert review. Clinical, laboratory, and radiologic data were manually abstracted. A nested case-control study was conducted to investigate risk factors for cholangitis in patients with ADPKD. Results We identified 29 cases of definite or suspected cholangitis complicating PLD (24 with ADPKD-associated PLD and 5 with ADPLD). Among patients with definite cholangitis in ADPKD-associated PLD (n=19) vs ADPLD (n=4), the mean ± SD age was 62.4±12.2 vs 55.1±8.6 years, and 9 (47.4%) vs 0 (0%), respectively, were male. The odds of gallstones (odds ratio [OR], 21.6; 95% CI, 3.17-927; P<.001), prior cholecystectomy (OR, 12.2; 95% CI, 1.59-552; P=.008), duodenal diverticulum (OR, 13.5; 95% CI, 2.44 to not estimable; P=.004), type 2 diabetes mellitus (OR, 6.41; 95% CI, 1.01 to not estimable; P=.05), prior endoscopic retrograde cholangiopancreatography (OR, 14.0; 95% CI, 1.80-631; P=.005), and prior kidney transplant (OR, 8.06; 95% CI, 1.72-76.0; P=.004) were higher in patients with ADPKD-associated PLD with definite cholangitis compared to controls. Conclusion Gallstones, prior cholecystectomy, duodenal diverticulosis, type 2 diabetes mellitus, prior endoscopic retrograde cholangiopancreatography, and prior kidney transplant constituted risk factors for cholangitis among patients with ADPKD-associated PLD.
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Key Words
- ADPKD, autosomal dominant polycystic kidney disease
- ADPLD, autosomal dominant polycystic liver disease
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- CT, computed tomography
- ERCP, endoscopic retrograde cholangiopancreatography
- ICD-10, International Classification of Diseases,Tenth Revision
- ICD-9, International Classification of Diseases,Ninth Revision
- MCR, Mayo Clinic, Rochester, MN
- MRI, magnetic resonance imaging
- OR, odds ratio
- PET, positron emission tomography
- PLD, polycystic liver disease
- T2DM, type 2 diabetes mellitus
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Affiliation(s)
- William P Martin
- Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Dublin, Republic of Ireland
| | - Lisa E Vaughan
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN
| | | | | | - Marie E Edwards
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Andrew Metzger
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Sarah R Senum
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Tetyana V Masyuk
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | - Matthew D Griffin
- Nephrology Services, Galway University Hospitals, Saolta University Healthcare Group, Galway, Republic of Ireland
| | - Ziad El-Zoghby
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Peter C Harris
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Walter K Kremers
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN
| | - David M Nagorney
- Department of Internal Medicine, and Division of Subspecialty General Surgery, Department of General Surgery, Mayo Clinic, Rochester, MN
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Vicente E Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Marie C Hogan
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
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van Aerts RMM, Kievit W, de Jong ME, Ahn C, Bañales JM, Reiterová J, Nevens F, Drenth JPH. Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry. Liver Int 2019; 39:575-582. [PMID: 30225933 DOI: 10.1111/liv.13965] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Revised: 07/26/2018] [Accepted: 09/09/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Polycystic liver disease (PLD) occurs in two genetic disorders, autosomal-dominant polycystic kidney disease (ADPKD) and autosomal-dominant polycystic liver disease (ADPLD). The aim of this study is to compare disease severity between ADPKD and ADPLD by determining the association between diagnosis and height-adjusted total liver volume (hTLV). METHODS We performed a cross-sectional analysis with hTLV as endpoint. Patients were identified from the International PLD Registry (>10 liver cysts) and included in our analysis when PLD diagnosis was made prior to September 2017, hTLV was available before volume-reducing therapy (measured on computed tomography or magnetic resonance imaging) and when patients were tertiary referred. Data from the registry were retrieved for age, diagnosis (ADPKD or ADPLD), gender, height and hTLV. RESULTS A total of 360 patients (ADPKD n = 241; ADPLD n = 119) met our inclusion criteria. Female ADPKD patients had larger hTLV compared with ADPLD (P = 0.008). In a multivariate regression analysis, ADPKD and lower age at index CT were independently associated with larger hTLV in females, whereas in males a higher age was associated with larger hTLV. Young females (≤51 years) had larger liver volumes compared with older females (>51 years) in ADPKD. CONCLUSION Aetiology is presented as a new risk factor associated with PLD severity. Young females with ADPKD represent a subgroup of PLD patients with the most severe phenotype expressed in hTLV.
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Affiliation(s)
- René M M van Aerts
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Wietske Kievit
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Michiel E de Jong
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Jesús M Bañales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute-Donostia University Hospital, IKERBASQUE, CIBERehd, University of the Basque Country (UPV/EHU), San Sebastián, Spain
| | - Jana Reiterová
- Department of Nephrology, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Leuven, Belgium
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
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Polyhedral Fenestration Technique Used for Combined Partial Hepatectomy and Cyst Fenestration for Polycystic Liver Disease: A Small Case Series. Int Surg 2019. [DOI: 10.9738/intsurg-d-17-00124.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective:
To assess the safety and efficacy of “polyhedral fenestration technique” (PFT), which we newly developed, in combined hepatectomy and cyst fenestration (CHCF) for symptomatic polycystic liver disease (PLD).
Summary of background data:
CHCF for PLD has been reportedly less efficacious for its invasiveness because 50% to 70% patients suffered recurrent symptoms after CHCF.
Methods:
Patient characteristics, intra- and early postoperative variables were compared between 5 PLD patients undergoing CHCF performed with PFT (PLD group) and 95 patients with diseases other than PLD receiving hepatectomy without biliary reconstruction during the same period (Control group) to assess safety of PFT. Chronological changes in total liver volume (TLV) measured by computed tomography (CT) volumetry as well as recurrent symptoms after CHCF were investigated to assess long-term outcomes.
Results:
Although ≧ Clavien-Dindo grade 2 complications were more common in the PLD group than in the Control group (PLD vs Control, 5/5[100%] vs 27/95[28%], p=0.004), patient characteristics, intra-, and early postoperative variables, including ≧ Clavien-Dindo grade 3 complications, were comparable among the 2 groups. Postoperative observational period of the 5 PLD patients ranged 30 to 88 months with a median of 63. CT volumetry revealed that TLV continued to reduce up to 1 year after surgery and thereafter retained less than 0.5 times of preoperative TLV in all patients. Recurrent liver enlargement or recurrent symptoms were not observed in any of the 5 PLD patients.
Conclusions:
Although our case series was very small, newly-developed PFT in CHCF for PLD yielded acceptable safety and excellent long-term outcomes.
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Initial experience with the use of tris-acryl gelatin microspheres for transcatheter arterial embolization for enlarged polycystic liver. Clin Exp Nephrol 2019; 23:825-833. [DOI: 10.1007/s10157-019-01714-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 02/01/2019] [Indexed: 12/30/2022]
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Aussilhou B, Dokmak S, Dondero F, Joly D, Durand F, Soubrane O, Belghiti J. Treatment of polycystic liver disease. Update on the management. J Visc Surg 2018; 155:471-481. [DOI: 10.1016/j.jviscsurg.2018.07.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Lin S, Shang TY, Wang MF, Lin J, Ye XJ, Zeng DW, Huang JF, Zhang NW, Wu YL, Zhu YY. Polycystic kidney and hepatic disease 1 gene mutations in von Meyenburg complexes: Case report. World J Clin Cases 2018; 6:296-300. [PMID: 30211211 PMCID: PMC6134282 DOI: 10.12998/wjcc.v6.i9.296] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Revised: 05/04/2018] [Accepted: 06/07/2018] [Indexed: 02/05/2023] Open
Abstract
Von Meyenburg complexes (VMCs) are a rare type of ductal plate malformation. We herein report two Chinese families with VMCs, and the suspicious gene mutation of this disease. Proband A was a 62-year-old woman with abnormal echographic presentation of the liver. She received magnetic resonance imaging (MRI) examination and liver biopsy, and the results showed she had VMCs. Histologically proved hepatocellular carcinoma was found 1 year after the diagnosis of VMCs. Proband B was a 57-year-old woman with intrahepatic diffuse lesions displayed by abdominal ultrasonography. Her final diagnoses were VMCs, congenital hepatic fibrosis, and hepatitis B surface e antigen-negative chronic hepatitis B after a series of examinations. Then, all the family members of both proband A and proband B were screened for VMCs by MRI or ultrasonography. The results showed that four of the 11 family members from two families, including two males and two females, were diagnosed with VMCs. DNA samples were extracted from the peripheral blood of those 11 individuals of two VMCs pedigrees and subjected to polymerase chain reaction amplification of the polycystic kidney and hepatic disease 1 (PKHD1) gene. Two different mutation loci were identified. Heterozygous mutations located in exon 32 (c.4280delG, p.Gly1427ValfsX6) in family A and exon 28 (c.3118C>T, p.Arg1040Ter) in family B were detected. We speculate that PKHD1 gene mutations may be responsible for the development of VMCs.
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Affiliation(s)
- Su Lin
- Liver Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Tian-Yu Shang
- Liver Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Ming-Fang Wang
- Liver Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Jian Lin
- Department of Hepato-Biliary-Pancreatic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Xiao-Jian Ye
- Department of Ultrasound, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Da-Wu Zeng
- Liver Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Jiao-Feng Huang
- Liver Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Nan-Wen Zhang
- Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yi-Long Wu
- Liver Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yue-Yong Zhu
- Liver Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
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Lanktree MB, Haghighi A, Guiard E, Iliuta IA, Song X, Harris PC, Paterson AD, Pei Y. Prevalence Estimates of Polycystic Kidney and Liver Disease by Population Sequencing. J Am Soc Nephrol 2018; 29:2593-2600. [PMID: 30135240 DOI: 10.1681/asn.2018050493] [Citation(s) in RCA: 185] [Impact Index Per Article: 26.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 07/27/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Estimating the prevalence of autosomal dominant polycystic kidney disease (ADPKD) is challenging because of age-dependent penetrance and incomplete clinical ascertainment. Early studies estimated the lifetime risk of ADPKD to be about one per 1000 in the general population, whereas recent epidemiologic studies report a point prevalence of three to five cases per 10,000 in the general population. METHODS To measure the frequency of high-confidence mutations presumed to be causative in ADPKD and autosomal dominant polycystic liver disease (ADPLD) and estimate lifetime ADPKD prevalence, we used two large, population sequencing databases, gnomAD (15,496 whole-genome sequences; 123,136 exome sequences) and BRAVO (62,784 whole-genome sequences). We used stringent criteria for defining rare variants in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5), and potential cystic disease modifiers; evaluated variants for quality and annotation; compared variants with data from an ADPKD mutation database; and used bioinformatic tools to predict pathogenicity. RESULTS Identification of high-confidence pathogenic mutations in whole-genome sequencing provided a lower boundary for lifetime ADPKD prevalence of 9.3 cases per 10,000 sequenced. Estimates from whole-genome and exome data were similar. Truncating mutations in ADPLD genes and genes of potential relevance as cyst modifiers were found in 20.2 cases and 103.9 cases per 10,000 sequenced, respectively. CONCLUSIONS Population whole-genome sequencing suggests a higher than expected prevalence of ADPKD-associated mutations. Loss-of-function mutations in ADPLD genes are also more common than expected, suggesting the possibility of unrecognized cases and incomplete penetrance. Substantial rare variation exists in genes with potential for phenotype modification in ADPKD.
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Affiliation(s)
- Matthew B Lanktree
- Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Amirreza Haghighi
- Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Elsa Guiard
- Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Ioan-Andrei Iliuta
- Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Xuewen Song
- Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Peter C Harris
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Andrew D Paterson
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; and.,Divisions of Epidemiology and.,Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - York Pei
- Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada;
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Hadžić N, Strazzabosco M. Fibropolycystic Liver Diseases and Congenital Biliary Abnormalities. SHERLOCK'S DISEASES OF THE LIVER AND BILIARY SYSTEM 2018:308-327. [DOI: 10.1002/9781119237662.ch16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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Besse W, Choi J, Ahram D, Mane S, Sanna-Cherchi S, Torres V, Somlo S. A noncoding variant in GANAB explains isolated polycystic liver disease (PCLD) in a large family. Hum Mutat 2018; 39:378-382. [PMID: 29243290 DOI: 10.1002/humu.23383] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Revised: 11/16/2017] [Accepted: 12/11/2017] [Indexed: 12/12/2022]
Abstract
Expanded mutation detection and novel gene discovery for isolated polycystic liver disease (PCLD) are necessary as 50% of cases do not have identified mutations in the seven published disease genes. We investigated a family with five affected siblings for which no loss-of-function variants were identified by whole exome sequencing analysis. SNP genotyping and linkage analysis narrowed the candidate regions to ∼8% of the genome, which included two published PCLD genes in close proximity to each other, GANAB and LRP5. Based on these findings, we re-evaluated the exome sequencing data and identified a novel intronic nine base pair deletion in the vicinity of the GANAB exon 24 splice donor that had initially been discarded by the sequence analysis pipelines. We used a minigene assay to show that this deletion leads to skipping of exon 24 in cell lines and primary human cholangiocytes. These findings prompt genomic evaluation beyond the coding region to enhance mutation detection in PCLD and to avoid premature implication of other genes in linkage disequilibrium.
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Affiliation(s)
- Whitney Besse
- Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - Jungmin Choi
- Department of Genetics, Yale University School of Medicine, New Haven, Connecticut
| | - Dina Ahram
- Department of Medicine, Columbia University, New York, New York
| | - Shrikant Mane
- Department of Genetics, Yale University School of Medicine, New Haven, Connecticut
| | | | - Vicente Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Stefan Somlo
- Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.,Department of Genetics, Yale University School of Medicine, New Haven, Connecticut
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Quaglia A, Roberts EA, Torbenson M. Developmental and Inherited Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2018:111-274. [DOI: 10.1016/b978-0-7020-6697-9.00003-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Wong MY, McCaughan GW, Strasser SI. An update on the pathophysiology and management of polycystic liver disease. Expert Rev Gastroenterol Hepatol 2017; 11:569-581. [PMID: 28317394 DOI: 10.1080/17474124.2017.1309280] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Polycystic liver disease (PLD) is characterized by the presence of multiple cholangiocyte-derived hepatic cysts that progressively replace liver tissue. They are classified as an inherited ciliopathy /cholangiopathy as pathology exists at the level of the primary cilia of cholangiocytes. Aberrant expression of the proteins in primary cilia can impair their structures and functions, thereby promoting cystogenesis. Areas covered: This review begins by looking at the epidemiology of PLD and its natural history. It then describes the pathophysiology and corresponding potential treatment strategies for PLD. Expert commentary: Traditionally, therapies for symptomatic PLD have been limited to symptomatic management and surgical interventions. Such techniques are not completely effective, do not alter the natural history of the disease, and are linked with high rate of re-accumulation of cysts. As a result, there has been a push for drugs targeted at abnormal cellular signaling cascades to address deregulated proliferation, cell dedifferentiation, apoptosis and fluid secretion. Currently, the only available drug treatments that halt disease progression and improve quality of life in PLD patients are somatostatin analogues. Numerous preclinical studies suggest that targeting components of the signaling pathways that influence cyst development can ameliorate growth of hepatic cysts.
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Affiliation(s)
- May Yw Wong
- a AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital and University of Sydney , Sydney , Australia
| | - Geoffrey W McCaughan
- a AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital and University of Sydney , Sydney , Australia
| | - Simone I Strasser
- a AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital and University of Sydney , Sydney , Australia
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Besse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. J Clin Invest 2017; 127:1772-1785. [PMID: 28375157 PMCID: PMC5409105 DOI: 10.1172/jci90129] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 02/09/2017] [Indexed: 02/06/2023] Open
Abstract
Dominantly inherited isolated polycystic liver disease (PCLD) consists of liver cysts that are radiologically and pathologically identical to those seen in autosomal dominant polycystic kidney disease, but without clinically relevant kidney cysts. The causative genes are known for fewer than 40% of PCLD index cases. Here, we have used whole exome sequencing in a discovery cohort of 102 unrelated patients who were excluded for mutations in the 2 most common PCLD genes, PRKCSH and SEC63, to identify heterozygous loss-of-function mutations in 3 additional genes, ALG8, GANAB, and SEC61B. Similarly to PRKCSH and SEC63, these genes encode proteins that are integral to the protein biogenesis pathway in the endoplasmic reticulum. We inactivated these candidate genes in cell line models to show that loss of function of each results in defective maturation and trafficking of polycystin-1, the central determinant of cyst pathogenesis. Despite acting in a common pathway, each PCLD gene product demonstrated distinct effects on polycystin-1 biogenesis. We also found enrichment on a genome-wide basis of heterozygous mutations in the autosomal recessive polycystic kidney disease gene PKHD1, indicating that adult PKHD1 carriers can present with clinical PCLD. These findings define genetic and biochemical modulators of polycystin-1 function and provide a more complete definition of the spectrum of dominant human polycystic diseases.
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Affiliation(s)
| | - Ke Dong
- Department of Internal Medicine, and
| | - Jungmin Choi
- Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA
| | | | | | - Murim Choi
- Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA
| | | | | | | | - James Knight
- Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Shrikant Mane
- Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Esa Tahvanainen
- Department of Medical Genetics, University of Helsinki, Helsinki, Finland
| | - Pia Tahvanainen
- Department of Medical Genetics, University of Helsinki, Helsinki, Finland
| | | | - Richard P. Lifton
- Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Terry Watnick
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - York P. Pei
- Division of Nephrology, University Health Network, Toronto, Ontario, Canada
| | - Vicente E. Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
| | - Stefan Somlo
- Department of Internal Medicine, and
- Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA
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Rajoriya N, Tripathi D, Leithead JA, Gunson BK, Lord S, Ferguson JW, Hirschfield GM. Portal hypertension in polycystic liver disease patients does not affect wait-list or immediate post-liver transplantation outcomes. World J Gastroenterol 2016; 22:9966-9973. [PMID: 28018103 PMCID: PMC5143763 DOI: 10.3748/wjg.v22.i45.9966] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Revised: 09/28/2016] [Accepted: 11/14/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To establish the impact of portal hypertension (PH) on wait-list/post-transplant outcomes in patients with polycystic liver disease (PCLD) listed for liver transplantation. METHODS A retrospective single-centre case controlled study of consecutive patients listed for liver transplantation over 12 years was performed from our centre. PH in the PCLD cohort was defined by the one or more of following parameters: (1) presence of radiological or endoscopic documented varices from our own centre or the referral centre; (2) splenomegaly (> 11 cm) on radiology in absence of splenic cysts accounting for increased imaging size; (3) thrombocytopenia (platelets < 150 × 109/L); or (4) ascites without radiological evidence of hepatic venous outflow obstruction from a single cyst. RESULTS Forty-seven PCLD patients (F: M = 42: 5) were listed for liver transplantation (LT) (single organ, n = 35; combined liver-kidney transplantation, n = 12) with 19 patients (40.4%) having PH. When comparing the PH group with non-PH group, the mean listing age (PH group, 50.6 (6.4); non-PH group, 47.1 (7.4) years; P = 0.101), median listing MELD (PH group, 12; non-PH group, 11; P = 0.422) median listing UKELD score (PH group, 48; non-PH group, 46; P = 0.344) and need for renal replacement therapy (P = 0.317) were similar. In the patients who underwent LT alone, there was no difference in the duration of ICU stay (PH, 3 d; non-PH, 2 d; P = 0.188), hospital stay length (PH, 9 d; non-PH, 10 d; P = 0.973), or frequency of renal replacement therapy (PH, 2/8; non-PH, 1/14; P = 0.121) in the immediate post-transplantation period. CONCLUSION Clinically apparent portal hypertension in patients with PCLD listed for liver transplantation does not appear to have a major impact on wait-list or peri-transplant morbidity.
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Utilization of Distilled Water Lavage for Localized Fluid Collection After Combined Hepatectomy and Cyst Fenestration for Polycystic Liver Disease. Int Surg 2016. [DOI: 10.9738/intsurg-d-16-00254.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Ascites necessitating persistent drainage or paracentesis after drain removal has been found among early postoperative complications after combined hepatectomy and cyst fenestration (CHCF) for polycystic liver disease (PLD). It has been reportedly observed in 20% to 70% of cases and seemed to easily cause recurrent symptoms unless properly treated. We utilized distilled water lavage for treating localized fluid collection after combined hepatectomy and cyst fenestration for PLD. A 63-year-old female patient underwent CHCF for PLD, which caused severe abdominal fullness. Early postoperative course was uneventful until 10 days after surgery when the patient suffered sudden abdominal fullness and resultant severe anorexia because of right subphrenic massive localized monolocular fluid collection diagnosed by abdominal computed tomography—although total liver volume was reduced to less than half of that before surgery. Percutaneous drainage relieved symptoms immediately, but the drainage tube could not be removed because of massive outflow. Then we utilized distilled water lavage for treating this condition. After that, drain outflow dramatically reduced and the drainage tube was successfully removed. Total liver volume of the patient continued to reduce up to 1 year after surgery and retained less than one-third of preoperative total liver volume thereafter. Sustained reduction of total liver volume in the present case suggested a sclerosant effect of hypotonic cytocidal property of distilled water for cyst endothelium and/or retrieved effectiveness of fenestration. Hence, we consider this approach to be useful for patients with PLD receiving CHCF and thus present it here.
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50
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Matsuura R, Honda K, Hamasaki Y, Doi K, Noiri E, Nangaku M. The Longitudinal Study of Liver Cysts in Patients With Autosomal Dominant Polycystic Kidney Disease and Polycystic Liver Disease. Kidney Int Rep 2016; 2:60-65. [PMID: 29142941 PMCID: PMC5678648 DOI: 10.1016/j.ekir.2016.09.061] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 09/22/2016] [Accepted: 09/27/2016] [Indexed: 12/13/2022] Open
Abstract
Introduction Although polycystic liver disease (PCLD) is one of the extrarenal complications in patients with autosomal dominant polycystic kidney disease (ADPKD), longitudinal changes and the association with total liver volume (TLV) have not been clearly elucidated yet. Methods Patients with ADPKD were chosen who underwent computed tomography or magnetic resonance imaging twice or more during August 2003 through December 2015. TLV, each cyst volume, and the proportion of parenchyma were measured. The natural history of liver cysts and the association between TLV and liver cysts were evaluated. To compare with liver cysts in ADPKD patients with PCLD, simple liver cysts in patients without ADPKD were also evaluated. Results TLV at baseline and its growth rate in all the patients with ADPKD, whose serum creatinine, estimated glomerular filtration rate, and total kidney volume were 1.45 mg/dl (0.76–2.32 mg/dl), 38.5 ml/min per 1.73 m2 (18.7–57.9 ml/min per 1.73 m2), and 1394 ml (773–2861 ml), were 1431 ml (1062–1749 ml) and −0.95%/yr (−3.16 to 4.94%/yr), respectively, in the observation period (median, 1063 days). Neither TLV nor its growth rate was significantly different between ADPKD patients with PCLD and those without PCLD. The growth rate of 79 liver cysts was 39.5%/yr (17.5–80.8%/yr) in PCLD patients with ADPKD. It was significantly larger than that of 60 simple liver cysts in the non-ADPKD group, 11.0%/yr (−2.2 to 33.1%/yr). Moreover, the proportion of parenchyma reduced, whereas that of total cyst volume increased significantly (P = 0.001). Discussion The reduction of parenchyma was accompanied by the growth of liver cysts during time course in PCLD patients with ADPKD.
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Affiliation(s)
- Ryo Matsuura
- Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan
| | - Kenjiro Honda
- Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan
| | - Yoshifumi Hamasaki
- Department of Hemodialysis and Apheresis, The University of Tokyo Hospital, Tokyo, Japan
| | - Kent Doi
- Department of Emergency and Critical Care Medicine, The University of Tokyo, Tokyo, Japan
| | - Eisei Noiri
- Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan
| | - Masaomi Nangaku
- Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan.,Department of Hemodialysis and Apheresis, The University of Tokyo Hospital, Tokyo, Japan
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