{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:49:34Z","timestamp":1780584574357,"version":"3.54.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background and aims<\/jats:title>\n<jats:p>To evaluate the ability of pretreatment liver stiffness measurements (pLSM) to predict hepatocellular carcinoma (HCC), incident decompensation and all-cause mortality in chronic hepatitis C (CHC) patients who achieved sustained virological response (SVR) after treatment with direct-acting antivirals (DAAs).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>773 CHC patients with SVR after DAA treatment and no prior liver complications were identified retrospectively. Optimized cut-off of 17.5 kPa for incident HCC was selected by maximum Youden\u2019s index. Patients were grouped by pLSM: &lt;10 kPa [reference], 10\u201317.4 kPa and \u226517.5 kPa. Primary outcomes were incident hepatocellular carcinoma and secondary outcomes were incident decompensated cirrhosis and all-cause mortality, analyzed using cox-regression.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Median follow-up was 36 months and 43.5% (336) had cirrhosis (LSM&gt;12.5 kPa). The median pLSM was 11.6 kPa (IQR 6.7\u201317.8, range 2.5\u201375) and pLSM of &lt;10 kPa, 10\u201317.4 kPa and 17.5\u201375 kPa was seen in 41.5%, 32.2% and 26.3%. During a median follow-up time of 36 months, 11 (1.4%) developed HCC, 14 (1.5%) developed decompensated cirrhosis, and 38 (4.9%) patients died. A pLSM of 17.5 kPa identified patients with a high risk of HCC with a negative predictive value of 98.9% and incidence rate of HCC in the 17.5\u201375 kPa group of 1.40\/100 person years compared to 0.14\/100 person years and 0.12\/100 person years in the 10\u201317.4 kPa and &lt;10 kPa groups, p&lt;0.001.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Pretreatment LSM predicts risk of HCC, decompensation and all-cause mortality in patients with SVR after DAA treatment. Patients with a pLSM &lt;17.5 kPa and no other risk factors for chronic liver disease appear not to benefit from HCC surveillance for the first 3 years after treatment. Longer follow-up is needed to clarify if they can be safely excluded from post treatment HCC screening hereafter.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0243725","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T19:37:09Z","timestamp":1607629029000},"page":"e0243725","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Low incidence of HCC in chronic hepatitis C patients with pretreatment liver stiffness measurements below 17.5 kilopascal who achieve SVR following DAAs"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7019-2269","authenticated-orcid":true,"given":"Jacob","family":"S\u00f8holm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne Fuglsang","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"M\u00f6ssner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit Thorup","family":"R\u00f8ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Lauersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper Bach","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3133-2724","authenticated-orcid":true,"given":"Nina","family":"Weis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toke 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with direct-acting antivirals","volume":"14","author":"I Rodriguez-Osorio","year":"2019","journal-title":"PloS one"},{"issue":"4","key":"pone.0243725.ref006","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.jhep.2016.06.019","article-title":"Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis","volume":"65","author":"MCM Cheung","year":"2016","journal-title":"Journal of hepatology"},{"key":"pone.0243725.ref007","article-title":"The dynamic effect of direct-acting antiviral treatments on the risk of hepatocellular carcinoma in patients with cirrhosis and chronic hepatitis C","author":"C Lusivika-Nzinga","year":"2019","journal-title":"Journal of viral hepatitis"},{"key":"pone.0243725.ref008","article-title":"EASL Recommendations on Treatment of Hepatitis C 2018","year":"2018","journal-title":"Journal of hepatology"},{"issue":"2","key":"pone.0243725.ref009","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1053\/j.gastro.2018.10.033","article-title":"What Are the Benefits of a Sustained Virologic Response to Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection?","volume":"156","author":"GN Ioannou","year":"2019","journal-title":"Gastroenterology"},{"issue":"5","key":"pone.0243725.ref010","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/joim.12972","article-title":"We know DAAs work, so now what? Simplifying models of care to enhance the hepatitis C cascade","volume":"286","author":"JV Lazarus","year":"2019","journal-title":"Journal of internal medicine"},{"issue":"7","key":"pone.0243725.ref011","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1053\/j.gastro.2011.02.058","article-title":"Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C","volume":"140","author":"J Vergniol","year":"2011","journal-title":"Gastroenterology"},{"issue":"10","key":"pone.0243725.ref012","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/apt.12307","article-title":"Non-invasive tests for fibrosis and liver stiffness predict 5-year survival of patients chronically infected with hepatitis B virus.","volume":"37","author":"V de Ledinghen","year":"2013","journal-title":"Alimentary pharmacology & therapeutics"},{"issue":"1","key":"pone.0243725.ref013","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/hep.27069","article-title":"Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C","volume":"60","author":"J Vergniol","year":"2014","journal-title":"Hepatology (Baltimore, Md)"},{"issue":"3","key":"pone.0243725.ref014","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.jhep.2015.05.022","article-title":"Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension","volume":"63","author":"R. de Franchis","year":"2015","journal-title":"Journal of hepatology"},{"key":"pone.0243725.ref015","first-page":"1","article-title":"Longitudinal evaluation of liver stiffness and outcomes in patients with chronic hepatitis C before and after short- and long-term IFN-free antiviral treatment","author":"C Stasi","year":"2019","journal-title":"Current medical research and opinion"},{"key":"pone.0243725.ref016","article-title":"Non-invasive prediction of liver related events in HCV compensated advanced chronic liver disease patients after oral antivirals","author":"M Pons","year":"2019","journal-title":"Journal of hepatology"},{"issue":"4","key":"pone.0243725.ref017","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jhep.2016.06.015","article-title":"Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals","volume":"65","author":"F Conti","year":"2016","journal-title":"Journal of hepatology"},{"issue":"6","key":"pone.0243725.ref018","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.cgh.2018.10.038","article-title":"Associated With Increased Risk of De Novo or Recurrent Hepatocellular Carcinoma in Patients With Cirrhosis Treated With Direct-Acting Antivirals for HCV Infection","volume":"17","author":"E Degasperi","year":"2019","journal-title":"FactorsClinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association"},{"issue":"6","key":"pone.0243725.ref019","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.dld.2018.02.010","article-title":"Hepatocellular carcinoma risk assessment by the measurement of liver stiffness variations in HCV cirrhotics treated with direct acting antivirals","volume":"50","author":"F Ravaioli","year":"2018","journal-title":"Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver"},{"key":"pone.0243725.ref020","unstructured":"Denmark S. Population in Denmark 2019 [cited 2019 8th October]. Available from: https:\/\/www.dst.dk\/en\/Statistik\/emner\/befolkning-og-valg\/befolkning-og-befolkningsfremskrivning\/folketal."},{"key":"pone.0243725.ref021","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/1471-2334-12-178","article-title":"Hepatitis C prevalence in Denmark -an estimate based on multiple national registers","volume":"12","author":"PB Christensen","year":"2012","journal-title":"BMC infectious diseases"},{"issue":"42","key":"pone.0243725.ref022","first-page":"2521","article-title":"The Danish Database for Hepatitis B and C","volume":"174","author":"N Weis","year":"2012","journal-title":"Ugeskrift for laeger"},{"issue":"3","key":"pone.0243725.ref023","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1002\/hep.25993","article-title":"Determination of reliability criteria for liver stiffness evaluation by transient elastography","volume":"57","author":"J Boursier","year":"2013","journal-title":"Hepatology (Baltimore, Md)"},{"issue":"8","key":"pone.0243725.ref024","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s10654-014-9930-3","article-title":"The Danish Civil Registration System as a tool in epidemiology","volume":"29","author":"M Schmidt","year":"2014","journal-title":"European journal of epidemiology"},{"issue":"7 Suppl","key":"pone.0243725.ref025","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1177\/1403494811401482","article-title":"The Danish National Patient Register","volume":"39","author":"E Lynge","year":"2011","journal-title":"Scandinavian journal of public health"},{"key":"pone.0243725.ref026","unstructured":"Authorities TDH. The Registry of Drug Abusers Undergoing Treatment 2019 [cited 2019 05\/08 2019]. Available from: https:\/\/sundhedsdatastyrelsen.dk\/da\/registre-og-services\/om-de-nationale-sundhedsregistre\/sygedomme-laegemidler-og-behandlinger\/stofmisbrugere-i-behandling."},{"issue":"7 Suppl","key":"pone.0243725.ref027","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1177\/1403494810393562","article-title":"The Danish Cancer Registry","volume":"39","author":"ML Gjerstorff","year":"2011","journal-title":"Scandinavian journal of public health"},{"issue":"7 Suppl","key":"pone.0243725.ref028","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1177\/1403494810393563","article-title":"The Danish Pathology Register","volume":"39","author":"B Bjerregaard","year":"2011","journal-title":"Scandinavian journal of public health"},{"issue":"7 Suppl","key":"pone.0243725.ref029","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1177\/1403494810394717","article-title":"The Danish National Prescription Registry","volume":"39","author":"HW Kildemoes","year":"2011","journal-title":"Scandinavian journal of public health"},{"key":"pone.0243725.ref030","unstructured":"Authorities TDH. National Registry of Alcohol Treatment 2019 [updated 10\/5\/2019; cited 2019 05\/08\/2019]. Available from: https:\/\/sundhedsdatastyrelsen.dk\/da\/registre-og-services\/om-de-nationale-sundhedsregistre\/sygedomme-laegemidler-og-behandlinger\/alkoholbehandlingsregisteret."},{"key":"pone.0243725.ref031","article-title":"Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study","author":"G Shiha","year":"2020","journal-title":"Journal of viral hepatitis"},{"issue":"2","key":"pone.0243725.ref032","doi-asserted-by":"crossref","first-page":"e0212036","DOI":"10.1371\/journal.pone.0212036","article-title":"Combining liver stiffness with hyaluronic acid provides superior prognostic performance in chronic hepatitis C","volume":"14","author":"JF Hansen","year":"2019","journal-title":"PloS one"},{"issue":"9","key":"pone.0243725.ref033","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/j.cgh.2018.12.018","article-title":"Cost Effectiveness of Hepatocellular Carcinoma Surveillance After a Sustained Virologic Response to Therapy in Patients With Hepatitis C Virus Infection and Advanced Fibrosis","volume":"17","author":"H Farhang Zangneh","year":"2019","journal-title":"Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association"},{"issue":"6","key":"pone.0243725.ref034","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1002\/hep.24545","article-title":"Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities","volume":"54","author":"JC Trinchet","year":"2011","journal-title":"Hepatology (Baltimore, Md)"},{"issue":"4","key":"pone.0243725.ref035","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1002\/hep.28895","article-title":"An assessment of benefits and harms of hepatocellular carcinoma surveillance in patients with cirrhosis","volume":"65","author":"O Atiq","year":"2017","journal-title":"Hepatology (Baltimore, Md)"},{"issue":"11","key":"pone.0243725.ref036","doi-asserted-by":"crossref","first-page":"e111912","DOI":"10.1371\/journal.pone.0111912","article-title":"Liver stiffness measurement among patients with chronic hepatitis B and C: results from a 5-year prospective study","volume":"9","author":"KM Christiansen","year":"2014","journal-title":"PloS one"},{"key":"pone.0243725.ref037","unstructured":"Echosens. Fibroscan recommendations. 2019 [cited 2020 16 01]. 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