{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:46:24Z","timestamp":1782323184662,"version":"3.54.5"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T00:00:00Z","timestamp":1553817600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie, Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Untreated, chronic hepatitis C virus (HCV) infection may lead to progressive liver damage, which can be mitigated by successful treatment. This integrated analysis reports the safety, efficacy, and pharmacokinetics (PK) of the ribavirin-free, direct-acting, antiviral, fixed-dose combination of glecaprevir\/pibrentasvir (G\/P) in patients with chronic HCV genotype 1\u20136 infections and compensated liver disease, including patients with chronic kidney disease stages 4 or 5 (CKD 4\/5).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from 9 Phase II and III clinical trials, assessing the efficacy and safety of G\/P treatment for 8\u201316 weeks, were included. The presence of cirrhosis was determined at screening using a liver biopsy, transient elastography, or serum biomarkers. The objectives were to evaluate safety, the rate of sustained virologic response at post-treatment week 12 (SVR12), and steady-state PK by cirrhosis status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 2369 patients, 308 (13%) were Child-Pugh Class A, including 20 with CKD 4\/5. Overall, &lt;1% of patients experienced an adverse event (AE) that led to G\/P discontinuation or G\/P-related serious AEs (SAEs). The most common AEs were headache and fatigue, occurring at similar frequencies with and without cirrhosis. SAEs were more common in patients with CKD 4\/5, but all were unrelated to G\/P. There were no cases of drug-induced liver injury or clinically relevant hepatic decompensation. SVR12 rates were 96.4% (297\/308) with compensated cirrhosis and 97.5% (2010\/2061) without cirrhosis. PK analysis demonstrated a 2.2-fold increase in glecaprevir exposure, but not pibrentasvir exposure, in patients with compensated cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>G\/P was safe and efficacious in patients with compensated liver disease, including those with CKD 4\/5.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trials Registration<\/jats:title><jats:p>NCT02243280, NCT02243293, NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, and NCT02446717<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciz022","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T22:42:51Z","timestamp":1548283371000},"page":"1657-1664","source":"Crossref","is-referenced-by-count":34,"title":["Safety and Pharmacokinetics of Glecaprevir\/Pibrentasvir in Adults With Chronic Genotype 1\u20136 Hepatitis C Virus Infections and Compensated Liver Disease"],"prefix":"10.1093","volume":"69","author":[{"given":"Edward","family":"Gane","sequence":"first","affiliation":[{"name":"Auckland Clinical Studies, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Poordad","sequence":"additional","affiliation":[{"name":"The Texas Liver Institute, University of Texas Health Science Center, San Antonio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neddie","family":"Zadeikis","sequence":"additional","affiliation":[{"name":"AbbVie Inc., North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin","family":"Valdes","sequence":"additional","affiliation":[{"name":"AbbVie Inc., North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"AbbVie Inc., North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"AbbVie Inc., North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armen","family":"Asatryan","sequence":"additional","affiliation":[{"name":"AbbVie Inc., North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Wang","sequence":"additional","affiliation":[{"name":"AbbVie Inc., North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Stedman","sequence":"additional","affiliation":[{"name":"Christchurch Hospital and University of Otago, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Greenbloom","sequence":"additional","affiliation":[{"name":"Toronto Digestive Disease Associates, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Research and Education, Inc, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdy","family":"Elkhashab","sequence":"additional","affiliation":[{"name":"Toronto Liver Centre, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus-Alexander","family":"W\u00f6rns","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsmedizin der Johannes-Gutenberg Universit\u00e4t, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Tran","sequence":"additional","affiliation":[{"name":"University Hospital of Nice, Digestive Centre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Mulkay","sequence":"additional","affiliation":[{"name":"H\u00f4pital Centre Hospitalier Universitaire 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Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"2019103013395783500_CIT0001","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/j.1365-2036.2010.04370.x","article-title":"Systematic review: outcome of compensated cirrhosis due to chronic hepatitis C infection","volume":"32","author":"Alazawi","year":"2010","journal-title":"Aliment Pharmacol Ther"},{"key":"2019103013395783500_CIT0002","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/cid\/civ860","article-title":"All-cause mortality and progression risks to hepatic decompensation and hepatocellular carcinoma in patients infected with hepatitis C virus","volume":"62","author":"Xu","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2019103013395783500_CIT0003","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s40261-015-0338-y","article-title":"Achieving sustained virological response in 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