Hepatitis Virus Diversity Research Unit (HVDRU), Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
Arch Virol. 2020 Aug;165(8):1815-1825. doi: 10.1007/s00705-020-04686-4. Epub 2020 Jun 5.
In South Africa (SA), hepatitis B virus (HBV) infection is strongly associated with hepatocellular carcinoma (HCC). As HBV genotypes/subgenotypes and mutations can influence disease manifestation and progression, our aim was to molecularly characterize HBV in Black cancer patients, with and without HCC. The basal core promoter/precore (BCP/PC) and complete surface (S) regions of HBV isolates were amplified and sequenced from 55 HCC cases and 22 non-HCC cancer controls. Phylogenetic analysis of 43 polymerase/complete S region amplicons showed that the majority (88.4%) clustered with subgenotype A1, 4.7% with A2, and 7% with A3. The following mutations were significantly more frequent in HCC cases than in controls (p < 0.05): in the BCP/PC 1753C/G (22.5% vs. 0%), 1764A (69.4% vs. 38.1%), and T64C (51.5% vs. 20%) in the preS2, which results in a F22L substitution. PreS1 and preS2 start codon mutants were detected only in HCC cases, occurring in two and 16 isolates, respectively. PreS deletion mutants were isolated from 11 HCC cases, which had a HBV viral load > 10,000 IU/mL and were significantly younger than non-HCC controls (34 ± 7.1 vs. 41.2 ± 9.5 years, p = 0.05). The 1762T/1764A double mutation was detected in the majority (90.9%) of the isolates from HCC cases with preS deletions. Black HBV carriers were mainly infected with subgenotype A1, with HCC cases carrying BCP/PC and preS mutant strains that are associated with hepatocarcinogenesis. This is the first study to compare the molecular characteristics of HBV from HCC and non-HCC cancer patients in SA.
在南非（SA），乙型肝炎病毒（HBV）感染与肝细胞癌（HCC）密切相关。由于 HBV 基因型/亚型和突变会影响疾病的表现和进展，我们的目的是对有和没有 HCC 的黑人癌症患者的 HBV 进行分子特征分析。从 55 例 HCC 病例和 22 例非 HCC 癌症对照中扩增和测序了 HBV 分离株的基本核心启动子/前核心（BCP/PC）和完整表面（S）区域。43 个聚合酶/完整 S 区扩增子的系统发育分析显示，大多数（88.4%）与亚基因型 A1 聚类，4.7%与 A2 聚类，7%与 A3 聚类。与对照组相比，以下突变在 HCC 病例中更为频繁（p<0.05）：BCP/PC 中的 1753C/G（22.5%比 0%）、1764A（69.4%比 38.1%）和 T64C（51.5%比 20%），这导致 F22L 取代。在 preS2 中检测到 preS2 起始密码子突变体仅在 HCC 病例中，分别发生在 2 个和 16 个分离株中。在 11 例 HCC 病例中分离到 preS 缺失突变体，这些病例的 HBV 病毒载量>10,000IU/mL，且明显比非 HCC 对照组年轻（34±7.1 岁比 41.2±9.5 岁，p=0.05）。在 HCC 病例中有 preS 缺失的大多数（90.9%）分离株中检测到 1762T/1764A 双重突变。黑人 HBV 携带者主要感染亚基因型 A1，HCC 病例携带与肝癌发生相关的 BCP/PC 和 preS 突变株。这是第一项比较南非 HCC 和非 HCC 癌症患者 HBV 分子特征的研究。
