[en] [en] 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.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Billiet, Antoon ; Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, European Reference Network on liver disease (ERN Rare-Liver), Leuven, Belgium
Temmerman, Frederik; Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, European Reference Network on liver disease (ERN Rare-Liver), Leuven, Belgium
Coudyzer, Walter; Department of Radiology, University Hospitals KU Leuven, Leuven, Belgium
Van den Ende, Natalie; Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, European Reference Network on liver disease (ERN Rare-Liver), Leuven, Belgium
Colle, Isabelle; Department of Gastroenterology and Hepatology, Algemeen Stedelijk Ziekenhuis Aalst, Aalst, Belgium
Francque, Sven; Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium
De Maeght, Stephane; Department of Gastroenterology and Hepatology, Grand Hôpital De Charleroi Saint-Joseph, Charleroi, Belgium
Janssens, Filip; Department of Gastroenterology and Hepatology, Jessa Ziekenhuis, Hasselt, Belgium
Orlent, Hans; Department of Gastroenterology and Hepatology, AZ Sint Jan Brugge, Brugge, Belgium
Sprengers, Dirk; Department of Gastroenterology and Hepatology, GZA Antwerp, Antwerpen, Belgium
Delwaide, Jean ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gastroentérologie, hépatologie, onco. digestive ; Department of Gastroenterology and Hepatology, C.H.U. de Liège, Liège, Belgium
Decock, Sofie; Department of Gastroenterology and Hepatology, AZ Sint Lucas Brugge, Brugge, Belgium
De Vloo, Charlotte; Department of Gastroenterology and Hepatology, AZ Delta, Roeselare, Belgium
Moreno, Christophe; Department of Gastroenterology and Hepatology, ULB Erasme, Brussels, Belgium
van Malenstein, Hannah; Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, European Reference Network on liver disease (ERN Rare-Liver), Leuven, Belgium
van der Merwe, Schalk; Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, European Reference Network on liver disease (ERN Rare-Liver), Leuven, Belgium
Verbeek, Jef; Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, European Reference Network on liver disease (ERN Rare-Liver), Leuven, Belgium
Nevens, Frederik; Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, European Reference Network on liver disease (ERN Rare-Liver), Leuven, Belgium
Data acquisition: Ho Thien Anh (Université Catholique de Louvain, Brussels), Dephine Degré (ULB Erasme, Brussels), Thierry Gustot (ULB Erasme, Brussels), Jean-Pierre Mulkay (Saint Pierre Brussels); Geert Robaeys (Ziekenhuis Oost-Limburg, Genk); Peter Michielsen (UZ Antwerpen); Luc Lasser (CHU Brugman, Brussels), Mike Cool (AZ Damiaan Oostende). Collection of the database: Natalie Van den Ende, Mitch Malavolta. Financial support of Ipsen for construction of the database.
Temmerman F, Missiaen L, Bammens B, Laleman W, Cassiman D, Verslype C, et al. Systematic review: the pathophysiology and management of polycystic liver disease. Aliment Pharmacol Ther. 2011;34(7):702–713. https://doi.org/10.1111/j.1365-2036.2011.04783.x
Boerrigter MM, Bongers EMHF, Lugtenberg D, Nevens F, Drenth JPH. Polycystic liver disease genes: practical considerations for genetic testing. Eur J Med Genet. 2021;64(3):104160. https://doi.org/10.1016/j.ejmg.2021.104160
EASL clinical practice guidelines on management of cystic liver diseases. J Hepatol 2022. S0168-8278(22)00347-6.
van Aerts RMM, Kievit W, de Jong ME, Ahn C, Bañales JM, Reiterová J, et al. Severity in polycystic liver disease is associated with aetiology and female gender: results of the International PLD Registry. Liver. 2019;39(3):575–582. https://doi.org/10.1111/liv.13965
van Aerts RMM, Bernts LHP, Gevers TJG, Kievit W, Koopmans L, Nieboer TE, et al. Estrogen-containing oral contraceptives are associated with polycystic liver disease severity in premenopausal patients. Clin Pharmacol Ther. 2019;106(6):1338–1345. https://doi.org/10.1002/cpt.1553
Gevers TJ, Inthout J, Caroli A, Ruggenenti P, Hogan MC, Torres VE, et al. Young women with polycystic liver disease respond best to somatostatin analogues: a pooled analysis of individual patient data. Gastroenterology. 2013;145(2):357–365. https://doi.org/10.1053/j.gastro.2013.04.055
Chebib FT, Jung Y, Heyer CM, Irazabal MV, Hogan MC, Harris PC, et al. Effect of genotype on the severity and volume progression of polycystic liver disease in autosomal dominant polycystic kidney disease. Nephrol Dial Transpl. 2016;31(6):952–960. https://doi.org/10.1093/ndt/gfw008
Temmerman F, Dobbels F, Ho TA, Pirson Y, Vanslembrouck R, Coudyzer W, et al. Development and validation of a polycystic liver disease complaint-specific assessment (POLCA). J Hepatol. 2014;61(5):1143–1150. https://doi.org/10.1016/j.jhep.2014.06.024
Wijnands TF, Neijenhuis MK, Kievit W, Nevens F, Hogan MC, Torres VE, et al. Evaluating health-related quality of life in patients with polycystic liver disease and determining the impact of symptoms and liver volume. Liver Int. 2014;34(10):1578–1583. https://doi.org/10.1111/liv.12430
Qian Q, Li A, King BF, Kamath PS, Lager DJ, Huston J, 3rd, et al. Clinical profile of autosomal dominant polycystic liver disease. Hepatology. 2003;37(1):164–171. https://doi.org/10.1053/jhep.2003.50006
Temmerman F, Ho TA, Vanslembrouck R, Coudyzer W, Billen J, Dobbels F, et al. Lanreotide reduces liver volume, but might not improve muscle wasting or weight loss, in patients with symptomatic polycystic liver disease. Clin Gastroenterol Hepatol. 2015;13(13):2353–2359. https://doi.org/10.1016/j.cgh.2015.05.039
Bernts LHP, Drenth JPH, Tjwa E. Management of portal hypertension and ascites in polycystic liver disease. Liver Int. 2019;39(11):2024–2033. https://doi.org/10.1111/liv.14245
D’Agnolo HM, Kievit W, van Munster KN, van der Laan JJ, Nevens F, Drenth JP. Center is an important indicator for choice of invasive therapy in polycystic liver disease. Transpl Int. 2017;30(1):76–82. https://doi.org/10.1111/tri.12875
van Keimpema L, Nevens F, Vanslembrouck R, van Oijen MG, Hoffmann AL, Dekker HM, et al. Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology. 2009;137(5):1661–1668. https://doi.org/10.1053/j.gastro.2009.07.052
Hogan MC, Masyuk TV, Page LJ, Kubly VJ, Bergstralh EJ, Li X, et al. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J Am Soc Nephrol. 2010;21(6):1052–1061. https://doi.org/10.1681/asn.2009121291
Griffiths J, Mills MT, Ong AC. Long-acting somatostatin analogue treatments in autosomal dominant polycystic kidney disease and polycystic liver disease: a systematic review and meta-analysis. BMJ Open. 2020;10(1):e032620. https://doi.org/10.1136/bmjopen-2019-032620
Suwabe T, Barrera FJ, Rodriguez-Gutierrez R, Ubara Y, Hogan MC. Somatostatin analog therapy effectiveness on the progression of polycystic kidney and liver disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One. 2021;16(9):e0257606. https://doi.org/10.1371/journal.pone.0257606
Neijenhuis MK, Gevers TJ, Nevens F, Hogan MC, Torres VE, Kievit W, et al. Somatostatin analogues improve health-related quality of life in polycystic liver disease: a pooled analysis of two randomised, placebo controlled trials. Aliment Pharmacol Ther. 2015;42(5):591–598. https://doi.org/10.1111/apt.13301
Pirenne J, Aerts R, Yoong K, Gunson B, Koshiba T, Fourneau I, et al. Liver transplantation for polycystic liver disease. Liver Transpl. 2001;7(3):238–245. https://doi.org/10.1053/jlts.2001.22178
van Keimpema L, Nevens F, Adam R, Porte RJ, Fikatas P, Becker T, et al. Excellent survival after liver transplantation for isolated polycystic liver disease: an Liver Transplant Registry study. Transpl Int. 2011;24(12):1239–1245. https://doi.org/10.1111/j.1432-2277.2011.01360.x
Neijenhuis MK, Gevers TJ, Hogan MC, Kamath PS, Wijnands TF, van den Ouweland RC, et al. Development and validation of a disease-specific questionnaire to assess patient-reported symptoms in polycystic liver disease. Hepatology. 2016;64(1):151–160. https://doi.org/10.1002/hep.28545
Temmerman F, Gevers T, Ho TA, Vanslembrouck R, Coudyzer W, van Pelt J, et al. Safety and efficacy of different lanreotide doses in the treatment of polycystic liver disease: pooled analysis of individual patient data. Aliment Pharmacol Ther. 2013;38(4):397–406. https://doi.org/10.1111/apt.12384
van Gastel MDA, Edwards ME, Torres VE, Erickson BJ, Gansevoort RT, Kline TL. Automatic measurement of kidney and liver volumes from MRimages of patients affected by autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2019;30(8):1514–1522. https://doi.org/10.1681/asn.2018090902
D’Agnolo HMA, Casteleijn NF, Gevers TJG, de Fijter H, van Gastel MDA, Messchendorp AL, et al. The association of combined total kidney and liver volume with pain and gastrointestinal symptoms in patients with later stage autosomal dominant polycystic kidney disease. Am J Nephrol. 2017;46(3):239–248. https://doi.org/10.1159/000479436
Tandon P, Ney M, Irwin I, Ma MM, Gramlich L, Bain VG, et al. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl. 2012;18(10):1209–1216. https://doi.org/10.1002/lt.23495
Arrazola L, Moonka D, Gish RG, Everson GT. Model for end-stage liver disease (MELD) exception for polycystic liver disease. Liver Transpl. 2006;12(S3):S110–S111. https://doi.org/10.1002/lt.20974
Caroli A, Antiga L, Cafaro M, Fasolini G, Remuzzi A, Remuzzi G, et al. Reducing polycystic liver volume in ADPKD: effects of somatostatin analogue octreotide. Clin J Am Soc Nephrol. 2010;5(5):783–789. https://doi.org/10.2215/cjn.05380709
Pisani A, Sabbatini M, Imbriaco M, Riccio E, Rubis N, Prinster A, et al. Long-term effects of octreotide on liver volume in patients with polycystic kidney and liver disease. ALADIN study group. Clin Gastroenterol Hepatol. 2016;14(7):1022–1030. https://doi.org/10.1016/j.cgh.2015.12.049
van Aerts RMM, Kievit W, D'Agnolo HMA, Blijdorp CJ, Casteleijn NF, Dekker SEI, et al. Lanreotide reduces liver growth in patients with autosomal dominant polycystic liver and kidney disease. Gastroenterology. 2019;157(2):481–491. https://doi.org/10.1053/j.gastro.2019.04.018
Aapkes SE, Barten TRM, Coudyzer W, Drenth JPH, Geijselaers IMA, Ter Grote SAM, et al. Validation of a semi-automatic method to measure total liver volumes in polycystic liver disease on computed tomography - high speed and accuracy. Eur Radiol. 2023. https://doi.org/10.1007/s00330-022-09346-6
Van Keimpema L, De Koning DB, Van Hoek B, Van Den Berg AP, Van Oijen MG, De Man RA, et al. Patients with isolated polycystic liver disease referred to liver centres: clinical characterization of 137 cases. Liver Int. 2011;31(1):92–98. https://doi.org/10.1111/j.1478-3231.2010.02247.x
