title: Impact of HCV core gene quasispecies on hepatocellular carcinoma risk among HALT-C trial patients.
abstract: Mutations at positions 70 and/or 91 in the core protein of genotype-1b, hepatitis C virus (HCV) are associated with hepatocellular carcinoma (HCC) risk in Asian patients. To evaluate this in a US population, the relationship between the percentage of 70 and/or 91 mutant HCV quasispecies in baseline serum samples of chronic HCV patients from the HALT-C trial and the incidence of HCC was determined by deep sequencing. Quasispecies percentage cut-points, ≥42% of non-arginine at 70 (non-R(70)) or ≥98.5% of non-leucine at 91 (non-L(91)) had optimal sensitivity at discerning higher or lower HCC risk. In baseline samples, 88.5% of chronic HCV patients who later developed HCC and 68.8% of matched HCC-free control patients had ≥42% non-R(70) quasispecies (P = 0.06). Furthermore, 30.8% of patients who developed HCC and 54.7% of matched HCC-free patients had quasispecies with ≥98.5% non-L(91) (P = 0.06). By Kaplan-Meier analysis, HCC incidence was higher, but not statistically significant, among patients with quasispecies ≥42% non-R(70) (P = 0.08), while HCC incidence was significantly reduced among patients with quasispecies ≥98.5% non-L(91) (P = 0.01). In a Cox regression model, non-R(70) ≥42% was associated with increased HCC risk. This study of US patients indicates the potential utility of HCV quasispecies analysis as a non-invasive biomarker of HCC risk.
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Shamy
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pendleton
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Eng
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Erin H
authors.initials: EH
authors.lastname: Doyle
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Bashir
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Branch
mesh_terms: D019943:Amino Acid Substitution; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000209:etiology / Q000821:virology; D005260:Female; D015870:Gene Expression; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D000074704:Quasispecies; D012367:RNA, Viral / Q000235:genetics*; D012306:Risk; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D014758:Viral Core Proteins