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This systematic review and meta\u2010analysis compared the efficacy and safety of two pan\u2010genotypic direct\u2010acting antiviral regimens, glecaprevir\/pibrentasvir (GLE\/PIB) and sofosbuvir\/velpatasvir (SOF\/VEL), for treating chronic HCV GT6. We followed PRISMA guidelines and searched PubMed, Embase, and the Cochrane Library for trials and studies. The primary outcome was the 12\u2010week sustained virologic response (SVR\n                    <jats:sub>12<\/jats:sub>\n                    ). We performed single\u2010arm meta\u2010analyses of proportions using methods robust for proportion data with prevalent boundary values and calculated the pooled risk difference (RD) for head\u2010to\u2010head comparisons. Twenty\u2010seven studies published between 2015 and 2025, comprising 1522 patients (451 GLE\/PIB and 1071 SOF\/VEL), were included. The pooled single\u2010arm SVR\n                    <jats:sub>12<\/jats:sub>\n                    rate for SOF\/VEL was a highly consistent 99.0% (95% Confidence Interval (CI): 98.2%\u201399.4%). The initial pooled rate for GLE\/PIB was 95.6% (95% CI: 93.2%\u201397.1%) with significant heterogeneity; however, a sensitivity analysis removing outlier studies yielded a rate of 99.2% (95% CI: 97.2%\u201399.8%) with no heterogeneity. Direct comparison across two studies found no significant difference in efficacy (pooled RD: 0.01, 95% CI: \u22120.01 to 0.02). Both regimens were exceptionally well\u2010tolerated, with treatment discontinuation rates near zero. GLE\/PIB and SOF\/VEL are clinically equivalent to treating HCV GT6, achieving near\u2010universal cure rates with excellent safety profiles. Regimen selection should consider practical factors such as GLE\/PIB's shorter 8\u2010week duration, comorbidities like cirrhosis, drug interaction profiles, and local cost\u2010effectiveness, rather than minor efficacy differences.\n                  <\/jats:p>","DOI":"10.1002\/rmv.70074","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:23:34Z","timestamp":1761218614000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Glecaprevir\/Pibrentasvir Versus Sofosbuvir\/Velpatasvir for Hepatitis C Virus Genotype 6: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"35","author":[{"given":"Duong Hoang Huy","family":"Le","sequence":"first","affiliation":[{"name":"Center of Excellence in Clinical Virology Department of Pediatrics Faculty of Medicine Chulalongkorn University  Bangkok Thailand"},{"name":"Medical Biochemistry &amp; Molecular Biology Department Fundamental Sciences and Basic Medical Sciences Pham Ngoc Thach University of Medicine  Ho Chi Minh Vietnam"},{"name":"Biomedical Research Center Pham Ngoc Thach University of Medicine  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinh Chuong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology University Medical Center  Ho Chi Minh City Vietnam"},{"name":"Faculty of Medicine Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sitthichai","family":"Kanokudom","sequence":"additional","affiliation":[{"name":"Center of Excellence in Clinical Virology Department of Pediatrics Faculty of Medicine Chulalongkorn University  Bangkok Thailand"},{"name":"Center of Excellence in Osteoarthritis and Musculoskeleton Faculty of Medicine Chulalongkorn University King Chulalongkorn Memorial Hospital Thai Red Cross Society  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiratchaya","family":"Puenpa","sequence":"additional","affiliation":[{"name":"Center of Excellence in Clinical Virology Department of Pediatrics Faculty of Medicine Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pornjarim","family":"Nilyanimit","sequence":"additional","affiliation":[{"name":"Center of Excellence in Clinical Virology Department of Pediatrics Faculty of Medicine Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anh Ngoc","family":"Tran","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sittisak","family":"Honsawek","sequence":"additional","affiliation":[{"name":"Center of Excellence in Osteoarthritis and Musculoskeleton Faculty of Medicine Chulalongkorn University King Chulalongkorn Memorial Hospital Thai Red Cross Society  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Poovorawan","sequence":"additional","affiliation":[{"name":"Center of Excellence in Clinical Virology Department of Pediatrics Faculty of Medicine Chulalongkorn University  Bangkok Thailand"},{"name":"Fellow of the Royal Society of Thailand (FRS[T]) the Royal Society of Thailand, Sanam Sueapa  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/livers4020013"},{"key":"e_1_2_13_3_1","unstructured":"World Health Organization (WHO) \u201cHepatitis C\u201d: [Updated on 9 April 2024]. 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