A survey on the detection of hepatitis B virus (HBV) in blood samples of patients with hepatocellular carcinoma (HCC) in China.

Abstract

e16178 Background: China is the country with the highest occurrence of HCC, accounting for about 45.3% of the new cases in the world. HBV can cause chronic infection and potentially leads to the occurrence of HCC. Generally, HBV genomic segments are able to be integrated into the host’s genome, then affect the expression of host genes, form carcinogenic proteins and cause chromosomal aberrations in host cells. HCC tumor tissue samples have more integration sites of HBV on the genome compared with para-cancerous tissues. It suggests that HBV is likely to be continuously enriched and integrated in the host genome during the development of HCC, and promotes the occurrence of HCC. There is plenty of tumor molecular information in the blood plasma of patients. Features of virus integration patterns and relatively quantitative level of virus DNA in the blood plasma should be intriguing to study. Methods: 216 blood samples of 178 HCC Chinese patients were collected. Circulating cell-free DNA (cfDNA) was processed by hybridization-based target enrichment and sequenced by next-generation sequencing (NGS) technique using Haplox HapOnco 680 panel. Results: In the blood of 178 HCC patients, the cfDNA of a total of 58 patients was detected with HBV genome fragments integration. These HBV genome fragments mainly belong to two subtypes, HBV-B and HBV-C, of which single HBV-B type was detected in 18 cases, accounting for 31% of HBV integrated infections, single HBV-C type was detected in 39 cases, accounting for 67.2% of HBV integrated infections. Additionally, HBV-B and HBV-C were co-integrated in 1 case. In the integrated host genome, the average number of breakpoints produced by HBV-B infection was 3.158, and the most frequent integration site was ANKRD26P1 (6 times). The average number of breakpoints produced by HBV-C integration was 3.65, and the most frequent integration site was TERT (15 times). There was no significant difference in the number of breakpoints produced between HBV-B and HBV-C groups (p=0.49). In the total of 58 HBV-B datasets and 64 HBV-C datasets, the average abundance of integrated HBV-B reads was 5.6e-05, and the average abundance of HBV-C was 5.04e-0.5, and there was no significant difference between them (p = 0.71). Conclusions: Approximately one third of the 178 HCC patients were detected positive for HBV integrationin their blood samples, with the ratio of subtypes HBV-B and HBV-C roughly 1:2. HBV-B is slightly lower than HBV-C in the number of average breakpoint, but the difference is not significant. Similarly, the overall abundance of HBV-B and HBV-C of integrated reads in blood is also quite similar. However, the hotspot integration sites of HBV-B and HBV-C on the host genome are quite different.