{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:23:31Z","timestamp":1790915011649,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A clear evidence on the benefits of somatostatin analogues (SA) on liver outcome in patients affected by polycystic liver disease is still lacking. We performed a meta-analysis of RCTs and a trial sequential analysis (TSA) evaluating the effects of SA in adult patients with polycystic liver disease on change in liver volume. As secondary outcome, we evaluated the effects on quality of life as measured by SF36-questionnaire. Six RCTs were selected with an overall sample size of 332 adult patients with polycystic liver disease (mean age: 46\u00a0years). Mean liver volume at baseline was 3289\u00a0ml in SA group and 3089\u00a0ml in placebo group. Overall, unstandardized mean difference in liver volume was \u2212\u2009176\u00a0ml (95%CI, \u2212\u2009406, 54; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.133). Heterogeneity was low (I<jats:sup>2<\/jats:sup>:0%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.992). However, we performed a moderator analysis and we found that a higher eGFR significantly correlates to a more pronounced effect of SA on liver volume reduction (<jats:italic>p<\/jats:italic>\u2009=\u20090.036). Cumulative Z-curve in TSA did not reach either significance and futility boundaries or required information size. Three RCTs have evaluated Quality of life parameters measured by SF36-QOL questionnaire for a total of 124 patients; no significant difference was found on the effect of SA on QOL parameters when compared with placebo. The present meta-analysis revealed a potential effect of SA on reduction of liver volume and quality of life parameters, but results did not reach a statistical significance. These data could be explained by the need of further studies, as demonstrated through TSA, to reach an adequate sample size to confirm the beneficial outcomes of SAs treatment.<\/jats:p>","DOI":"10.1038\/s41598-021-02812-z","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T11:06:13Z","timestamp":1638788773000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The effects of somatostatin analogues on liver volume and quality of life in polycystic liver disease: a meta-analysis of randomized controlled trials"],"prefix":"10.1038","volume":"11","author":[{"given":"Carlo","family":"Garofalo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Capuano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Pennino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"De Gregorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Riccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Provenzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Crocetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Buonanno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savio Domenico","family":"Pandolfo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Andreucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pisani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"issue":"6","key":"2812_CR1","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1016\/j.ajhg.2016.05.004","volume":"98","author":"B Porath","year":"2016","unstructured":"Porath, B. et al. Mutations in GANAB, encoding the glucosidase II\u03b1 subunit, cause autosomal-dominant polycystic kidney and liver disease. Am. J. Hum. Genet. 98(6), 1193\u20131207 (2016).","journal-title":"Am. J. Hum. Genet."},{"issue":"5","key":"2812_CR2","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.ajhg.2018.03.013","volume":"102","author":"E Cornec-Le Gall","year":"2018","unstructured":"Cornec-Le Gall, E. et al. Monoallelic mutations to DNAJB11 cause atypical autosomal-dominant polycystic kidney disease. Am. J. Hum. Genet. 102(5), 832\u2013844 (2018).","journal-title":"Am. J. Hum. Genet."},{"issue":"8","key":"2812_CR3","first-page":"1356","volume":"32","author":"CJ Willey","year":"2017","unstructured":"Willey, C. J. et al. Prevalence of autosomal dominant polycystic kidney disease in the European Union. Nephrol. Dial. Transplant. 32(8), 1356\u20131363 (2017).","journal-title":"Nephrol. Dial. Transplant."},{"issue":"9569","key":"2812_CR4","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1016\/S0140-6736(07)60601-1","volume":"369","author":"VE Torres","year":"2007","unstructured":"Torres, V. E., Harris, P. C. & Pirson, Y. Autosomal dominant polycystic kidney disease. Lancet 369(9569), 1287\u20131301 (2007).","journal-title":"Lancet"},{"issue":"10","key":"2812_CR5","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.1681\/ASN.2018050493","volume":"29","author":"MB Lanktree","year":"2018","unstructured":"Lanktree, M. B. et al. Prevalence estimates of polycystic kidney and liver disease by population sequencing. J. Am. Soc. Nephrol. 29(10), 2593\u20132600 (2018).","journal-title":"J. Am. Soc. Nephrol."},{"issue":"4","key":"2812_CR6","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.jhep.2017.11.024","volume":"68","author":"RMM van Aerts","year":"2018","unstructured":"van Aerts, R. M. M., van de Laarschot, L. F. M., Banales, J. M. & Drenth, J. P. H. Clinical management of polycystic liver disease. J. Hepatol. 68(4), 827\u2013837 (2018).","journal-title":"J. Hepatol."},{"key":"2812_CR7","doi-asserted-by":"publisher","first-page":"64","DOI":"10.2215\/CJN.00080605","volume":"1","author":"KT Bae","year":"2006","unstructured":"Bae, K. T. et al. Magnetic resonance imaging evaluation of hepatic cysts in early autosomal dominant polycystic kidney disease: the consortium for radiologic imaging studies of polycystic kidney disease cohort. Clin. J. Am. Soc. Nephrol. 1, 64\u201369 (2006).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"issue":"3","key":"2812_CR8","first-page":"179","volume":"4","author":"GT Everson","year":"2008","unstructured":"Everson, G. T. Polycystic liver disease. Gastroenterol. Hepatol. (N Y). 4(3), 179\u2013181 (2008).","journal-title":"Gastroenterol. Hepatol. (N Y)."},{"issue":"8","key":"2812_CR9","doi-asserted-by":"publisher","first-page":"950","DOI":"10.2174\/1389450116666150427161743","volume":"18","author":"TV Masyuk","year":"2017","unstructured":"Masyuk, T. V., Masyuk, A. I. & La Russo, N. F. Therapeutic targets in polycystic liver disease. Curr. Drug Targets. 18(8), 950\u2013957 (2017).","journal-title":"Curr. Drug Targets."},{"issue":"10","key":"2812_CR10","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1111\/liv.12430","volume":"34","author":"TFM Wijnands","year":"2014","unstructured":"Wijnands, T. F. M. 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. 34(10), 1578\u20131583 (2014).","journal-title":"Liver Int."},{"issue":"6","key":"2812_CR11","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1111\/j.1523-1755.2005.00748.x","volume":"68","author":"G Fuiano","year":"2005","unstructured":"Fuiano, G. et al. Early detection of progressive renal dysfunction in patients with coronary artery disease. Kidney Int. 68(6), 2773\u20132780 (2005).","journal-title":"Kidney Int."},{"issue":"7","key":"2812_CR12","doi-asserted-by":"publisher","first-page":"314","DOI":"10.3389\/fcell.2019.00314","volume":"3","author":"M Provenzano","year":"2019","unstructured":"Provenzano, M. et al. Unraveling cardiovascular risk in renal patients: a new take on old tale. Front. Cell Dev. Biol. 3(7), 314 (2019).","journal-title":"Front. Cell Dev. Biol."},{"issue":"6","key":"2812_CR13","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1002\/hep.24036","volume":"52","author":"JP Drenth","year":"2010","unstructured":"Drenth, J. P., Chrispijn, M., Nagorney, D. M., Kamath, P. S. & Torres, V. E. Medical and surgical treatment options for polycystic liver disease. Hepatology 52(6), 2223\u20132230 (2010).","journal-title":"Hepatology"},{"issue":"3","key":"2812_CR14","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1097\/MOG.0b013e328343433f","volume":"27","author":"TJ Gevers","year":"2011","unstructured":"Gevers, T. J. & Drenth, J. P. Somatostatin analogues for treatment of polycystic liver disease. Curr. Opin. Gastroenterol. 27(3), 294\u2013300 (2011).","journal-title":"Curr. Opin. Gastroenterol."},{"issue":"7","key":"2812_CR15","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1111\/j.1365-2036.2011.04783.x","volume":"34","author":"F Temmerman","year":"2011","unstructured":"Temmerman, F. et al. Systematic review: the pathophysiology and management of polycystic liver disease. Aliment. Pharmacol. Ther. 34(7), 702\u2013713 (2011).","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"5","key":"2812_CR16","doi-asserted-by":"publisher","first-page":"783","DOI":"10.2215\/CJN.05380709","volume":"5","author":"A Caroli","year":"2010","unstructured":"Caroli, A. et al. Reducing polycystic liver volume in ADPKD: effects of somatostatin analogue octreotide. Clin. J. Am. Soc. Nephrol. 5(5), 783\u2013789 (2010).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"issue":"6","key":"2812_CR17","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1681\/ASN.2009121291","volume":"21","author":"MC Hogan","year":"2010","unstructured":"Hogan, M. C. et al. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J. Am. Soc. Nephrol. 21(6), 1052\u20131061 (2010).","journal-title":"J. Am. Soc. Nephrol."},{"issue":"5","key":"2812_CR18","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1053\/j.gastro.2009.07.052","volume":"137","author":"L van Keimpema","year":"2009","unstructured":"van Keimpema, L. et al. Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 137(5), 1661\u20131668 (2009).","journal-title":"Gastroenterology"},{"issue":"5","key":"2812_CR19","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1053\/j.gastro.2019.04.018","volume":"157","author":"RMM van Aerts","year":"2019","unstructured":"van Aerts, R. M. M., Kievit, W., D'Agnolo, H. M. A., Blijdorp, C. J., Casteleijn, N. F. et al. DIPAK-1 Investigators. Lanreotide Reduces Liver Growth In Patients With Autosomal Dominant Polycystic Liver and Kidney Disease. Gastroenterology 157(2), 481\u2013491.e7 (2019).","journal-title":"Gastroenterology"},{"key":"2812_CR20","doi-asserted-by":"crossref","unstructured":"Pisani, A., Sabbatini, M, Imbriaco, M. et al.; ALADIN Study Group. Long-term effects of octreotide on liver volume in patients with polycystic kidney and liver disease. Clin. Gastroenterol. Hepatol. 14(7), 1022\u20131030.e4 (2016).","DOI":"10.1016\/j.cgh.2015.12.049"},{"issue":"1","key":"2812_CR21","doi-asserted-by":"publisher","first-page":"e032620","DOI":"10.1136\/bmjopen-2019-032620","volume":"10","author":"J Griffiths","year":"2020","unstructured":"Griffiths, J., Mills, M. T. & Ong, A. C. Long-acting somatostatin analogue treatments in autosomal dominant polycystic kidney disease and polycystic liver disease: a systematic review and meta-analysis. BMJ Open 10(1), e032620 (2020).","journal-title":"BMJ Open"},{"issue":"9","key":"2812_CR22","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.2215\/CJN.13661119","volume":"15","author":"MC Hogan","year":"2020","unstructured":"Hogan, M. C. et al. Pansomatostatin agonist pasireotide long-acting release for patients with autosomal dominant polycystic kidney or liver disease with severe liver involvement: a randomized clinical trial. Clin. J. Am. Soc. Nephrol. 15(9), 1267\u20131278 (2020).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"2812_CR23","doi-asserted-by":"crossref","unstructured":"Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G.; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 6, e1000097 (2009).","DOI":"10.1371\/journal.pmed.1000097"},{"key":"2812_CR24","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928","volume":"343","author":"JP Higgins","year":"2011","unstructured":"Higgins, J. P. et al. The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials. BMJ 343, d5928. https:\/\/doi.org\/10.1136\/bmj.d5928 (2011).","journal-title":"BMJ"},{"key":"2812_CR25","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JP Higgins","year":"2003","unstructured":"Higgins, J. P., Thompson, S. G., Deeks, J. J. & Altman, D. G. Measuring inconsistency in meta-analyses. BMJ 327, 557\u2013560 (2003).","journal-title":"BMJ"},{"key":"2812_CR26","first-page":"15","volume":"8","author":"A Tobias","year":"1999","unstructured":"Tobias, A. Assessing the influence of a single study in the meta-analysis estimate. Stata Tech. Bull. 8, 15\u201317 (1999).","journal-title":"Stata Tech. Bull."},{"key":"2812_CR27","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1002\/sim.1040","volume":"21","author":"HC Van Houwelingen","year":"2002","unstructured":"Van Houwelingen, H. C., Arends, L. R. & Stijnen, T. Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat. Med. 21, 589\u2013624 (2002).","journal-title":"Stat. Med."},{"key":"2812_CR28","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.2307\/2533446","volume":"50","author":"CB Begg","year":"1994","unstructured":"Begg, C. B. & Mazumdar, M. Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 1088\u20131101 (1994).","journal-title":"Biometrics"},{"key":"2812_CR29","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrgastro.2012.254","volume":"10","author":"TJ Gevers","year":"2013","unstructured":"Gevers, T. J. & Drenth, J. P. Diagnosis and management of polycystic liver disease. Nat. Rev. Gastroenterol. Hepatol. 10, 101\u2013108 (2013).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"9","key":"2812_CR30","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1750-1172-9-69","volume":"01","author":"WR Cnossen","year":"2014","unstructured":"Cnossen, W. R. & Drenth, J. P. Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management. Orphanet. J. Rare Dis. 01(9), 69 (2014).","journal-title":"Orphanet. J. Rare Dis."},{"issue":"5","key":"2812_CR31","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1111\/apt.13301","volume":"42","author":"MK Neijenhuis","year":"2015","unstructured":"Neijenhuis, M. K. 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. 42(5), 591\u2013598 (2015).","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"3","key":"2812_CR32","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1111\/liv.13965","volume":"39","author":"RMM van Aerts","year":"2019","unstructured":"van Aerts, R. M. M. et al. Severity in polycystic liver disease is associated with aetiology and female gender: results of the International PLD Registry. Liver Int. 39(3), 575\u2013582 (2019).","journal-title":"Liver Int."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02812-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02812-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02812-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T17:56:01Z","timestamp":1670090161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02812-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,6]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2812"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-02812-z","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,6]]},"assertion":[{"value":"17 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23500"}}