Analysis of HBV Genome Integration in Patients With HBV-Previously Infected NBNC-HCC

IF 3.7 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Research Pub Date : 2026-07-07 Epub Date: 2026-03-24 DOI:10.1111/hepr.70163

Tomoya Saito, Rigel Suzuki, Akhinur Rahman, Kento Mori, Samiul Alam Rajib, Nobuhiro Kobayashi, Yoichi Yamamoto, Sharmin Nahar Sithi, Takaya Ichikawa, Tatsuya Orimo, Tatsuhiko Kakisaka, Lihan Liang, Naganori Nao, Saori Suzuki, Tomokazu Tamura, Yorifumi Satou, Akinobu Taketomi, Takasuke Fukuhara

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引用次数: 0

Abstract

Aim

The incidence of non-B non-C hepatocellular carcinoma (NBNC-HCC), which is negative for Hepatitis B surface antigen and Hepatitis C virus antibodies, is on the rise. Relatively higher numbers of NBNC-HCC patients are Hepatitis B core antibody (HBcAb) positive, suggesting that previous HBV infection may play a role in NBNC-HCC development, though the exact mechanisms are unclear. This study aimed to investigate whether HBV genomes are integrated into the host genome of HBcAb-positive NBNC-HCC cases and how these integrations may contribute to cancer development and progression.

Methods

HBV detection PCR using HBV-specific primers on DNA extracted from HBcAb-positive NBNC-HCC tissue samples was performed. Positive samples were further examined for HBV integration sites using Viral DNA-Capture sequencing Approach. Additionally, Hepatitis B core–related antigen (HBcrAg) serum levels were measured to assess whether they could be predictive for HBV detection PCR results.

Results

Among 90 HBcAb-positive NBNC-HCC samples, HBV genome amplification was detected in 19 samples, and differences in HBcrAg status were observed according to HBV detection PCR results. Eighteen of these samples showed HBV integration. The HBV genome was integrated near the TERT gene in 7 samples, resulting in significantly increased TERT mRNA levels, in the KMT2B gene (3 samples), and downstream of the LOC441666 gene (2 samples).

Conclusion

The integration sites we identified in our samples have been previously reported in HBV-related HCC, suggesting that HBV integration may also contribute to hepatocarcinogenesis in HBcAb-positive NBNC-HCC. Furthermore, HBcrAg could serve as a potential, noninvasive marker for detecting the HBV genome in these cases.

Abstract Image

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HBV-既往感染的NBNC-HCC患者的HBV基因组整合分析

目的：乙型肝炎表面抗原和丙型肝炎病毒抗体阴性的非乙型非丙型肝细胞癌（NBNC-HCC）的发病率呈上升趋势。乙型肝炎核心抗体（HBcAb）阳性的NBNC-HCC患者相对较多，提示先前的HBV感染可能在NBNC-HCC的发展中起作用，尽管确切的机制尚不清楚。本研究旨在探讨HBV基因组是否整合到hbcab阳性的NBNC-HCC病例的宿主基因组中，以及这些整合如何促进癌症的发生和进展。方法：采用HBV特异性引物对hbcab阳性的NBNC-HCC组织样本提取的DNA进行HBV检测PCR。阳性样本使用病毒dna捕获测序方法进一步检测HBV整合位点。此外，还测量了乙型肝炎核心相关抗原（HBcrAg）血清水平，以评估它们是否可以预测HBV检测PCR结果。结果：90例hbcab阳性的NBNC-HCC样本中，有19例检测到HBV基因组扩增，根据HBV检测PCR结果观察HBcrAg状态的差异。其中18个样本显示HBV整合。在7个样本中，HBV基因组在TERT基因附近整合，导致KMT2B基因（3个样本）和LOC441666基因下游（2个样本）的TERT mRNA水平显著升高。结论：我们在样本中发现的整合位点之前已经在HBV相关的HCC中报道过，这表明HBV整合也可能有助于hbcab阳性的NBNC-HCC的肝癌发生。此外，在这些病例中，HBcrAg可以作为一种潜在的、无创的检测HBV基因组的标记物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hepatology Research 医学-胃肠肝病学

CiteScore

8.30

自引率

14.30%

发文量

124

审稿时长

1 months

期刊介绍： Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.