Korba Brent, Shetty Kirti, Medvedev Alexei, Viswanathan Prasanth, Varghese Rency, Zhou Bin, Roy Rabindra, Makambi Kepher, Ressom Habtom, Loffredo Christopher A
Department of Microbiology and Immunology, Georgetown University, Washington, DC 20057, USA.
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
J Gen Virol. 2015 Sep;96(9):2928-2937. doi: 10.1099/jgv.0.000219. Epub 2015 Jul 3.
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.
丙型肝炎病毒1b型（HCV GT1b）核心基因密码子70和91的特定序列变化与肝细胞癌（HCC）风险增加有关。基本上，之前所有的研究都是在患有各种肝病的亚洲人群中进行的，没有一项研究是专门针对感染GT1a的个体进行的。我们在美国一个多民族的HCV相关肝硬化人群中进行了一项试点研究，以确定这种关联是否也适用于感染GT1a的个体，并确定HCV核心基因中的其他序列变化是否与HCC风险相关。使用基于标准逆转录聚合酶链反应（RT-PCR）的方法分析了90名患有肝硬化的GT1 HCV携带者（42名患有HCC）血清中的HCV核心基因序列。将核苷酸序列数据与GenBank中可用的参考序列进行了比较。密码子91序列变化的频率在HCC（7/19）和非HCC（11/22）的GT1b携带者之间没有统计学差异。在GT1a携带者中，密码子91的序列变化比GT1b携带者少见，但在非HCC受试者中未观察到（4/23对0/26，P = 0.03，Fisher精确检验）。密码子70的序列变化在HCC和非HCC的GT1a和1b携带者之间分布没有差异。最重要的是，对于GT1a携带者，一组特定的其他密码子核苷酸变化在所有HCC患者中均有出现，但在任何非HCC患者中均未出现。该检测组在GT1a感染个体中早期检测HCC的效用需要在更大的人群中进行评估，包括纵向研究。
