| Author |
Korba, Brent Shetty, Kirti Medvedev, Alexei Viswanathan, Prasanth Varghese, Rency Zhou, Bin Roy, Rabindra Makambi, Kepher Ressom, Habtom Loffredo, Christopher A. |
| Description |
Country affiliation: United States Author Affiliation: Korba B ( 1âDepartment of Microbiology and Immunology, Georgetown University, Washington, DC 20057, USA 2âLombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.); Shetty K ( 3âDivision of Gastroenterology & Hepatology, Johns Hopkins University, Sibley Memorial Hospital, Washington, DC 20016, USA.); Medvedev A ( 1âDepartment of Microbiology and Immunology, Georgetown University, Washington, DC 20057, USA.); Viswanathan P ( 1âDepartment of Microbiology and Immunology, Georgetown University, Washington, DC 20057, USA.); Varghese R ( 4âDepartment of Oncology, Georgetown University, Washington, DC 20057, USA.); Zhou B ( 4âDepartment of Oncology, Georgetown University, Washington, DC 20057, USA.); Roy R ( 4âDepartment of Oncology, Georgetown University, Washington, DC 20057, USA.); Makambi K ( 5âDepartment of Biostatistics, Georgetown University, Washington, DC 20057, USA.); Ressom H ( 4âDepartment of Oncology, Georgetown University, Washington, DC 20057, USA.); Loffredo CA ( 5âDepartment of Biostatistics, Georgetown University, Washington, DC 20057, USA 4âDepartment of Oncology, Georgetown University, Washington, DC 20057, USA.) |
| Abstract |
Specific sequence changes in codons 70 and 91 of the hepatitis C virus genotype 1b (HCV GT1b) core gene have been associated with increased risk of hepatocellular carcinoma (HCC). Essentially all previous studies were conducted in Asian populations with a wide range of liver disease, and none were conducted specifically in GT1a-infected individuals. We conducted a pilot study in a multiethnic population in the USA with HCV-related cirrhosis to determine if this association extended to GT1a-infected individuals and to determine if other sequence changes in the HCV core gene were associated with HCC risk. HCV core gene sequences from sera of 90 GT1 HCV carriers with cirrhosis (42 with HCC) were analysed using standard RT-PCR-based procedures. Nucleotide sequence data were compared with reference sequences available from GenBank. The frequency of sequence changes in codon 91 was not statistically different between HCC (7/19) and non-HCC (11/22) GT1b carriers. In GT1a carriers, sequence changes in codon 91 were observed less often than in GT1b carriers but were not observed in non-HCC subjects (4/23 vs 0/26, P = 0.03, Fisher's exact test). Sequence changes in codon 70 were not distributed differently between HCC and non-HCC GT1a and 1b carriers. Most importantly, for GT1a carriers, a panel of specific nucleotide changes in other codons was collectively present in all subjects with HCC, but not in any of the non-HCC patients. The utility of this test panel for early detection of HCC in GT1a-infected individuals needs to be assessed in larger populations, including longitudinal studies. |
