Impact of HCV core gene quasispecies on hepatocellular carcinoma risk among HALT-C trial patients

Ahmed El-Shamy, Matthew Pendleton, Francis J. Eng, Erin H. Doyle, Ali Bashir, Andrea D. Branch

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16 Scopus citations


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.

Original languageEnglish
Article number27025
JournalScientific Reports
StatePublished - 1 Jun 2016


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