肝移植后 hcc 复发中通过 hbv 整合子复制的三角肝炎病毒（hdv）

IF 4 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Digestive and Liver Disease Pub Date : 2024-09-01 DOI:10.1016/j.dld.2024.08.030

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引用次数: 0

摘要

一名感染 HCV/HBV-HDV/HIV 的男性吸毒者于 2012 年因 HCC 接受了肝移植手术（LT），当时他 52 岁。HCC 组织显示 HDV-RNA 高（88,400 拷贝/细胞），HBV-DNA 总量低（0.00001 c/c），HBVcccDNA0.00008 c/c），未检测到 HBV-RNA。高通量 HBV 整合测序（HBIS）确定了 657 个 HBV 整合位点。LT后，给予他克莫司、比特格韦/恩曲他滨/TAF和抗HBs免疫球蛋白，结果HBsAg、HDV-RNA和HCV-RNA阴性。2018年，观察到HBsAg逆转，检测不到HBV-DNA和HDV-RNA>19,000 c/ml.2019年，发生HDV相关肝炎。肝内 HBcAg、HBsAgHBV DNA、HBVcccDNA 和 HBV-RNA 均检测不到。肝脏中的 HDV RNA 浓度非常高（3,920,000 c/c），但血清中的浓度却很低（214 IU/mL）。CT 扫描（CT）怀疑左侧肾上腺有孤立的 HCC 复发，肾上腺切除术证实了这一点。肾上腺肿瘤中的实时 PCR 显示 HDV RNA 水平较高（5.5 c/c），但 HBV DNA（0.00009 c/c）和 HBVcccDNA（0.00001 c/c）水平较低。检测不到 HBV RNA。HBIS 发现了 3497 个 HBV 整合点，其中大部分包括 HBs 基因序列。肾上腺切除术后，HBsAg 和 HDV-RNA 检测不到。2021 年，CT 显示肝脏有两个 HCC 结节，右侧肾上腺有一个。2023 年，出现新的 HDV 肝炎，HDV-RNA>3,631,360 UI/ml，HBV-DNA <10UI/ml。针对 HCC 的进展，对右侧肾上腺进行了 RFA，并开始使用布来韦肽。3 个月后，HDV-RNA 为 48,638 c/ml，转氨酶正常。该病例表明，尽管 HBVcccDNA 水平较低，但肝外 HCC 复发中仍存在 HDV 复制。经过 RFA 和 BLV 治疗后，HDV RNA 水平下降，这表明 HCC 转移灶可能是 HBV 整合后 HBsAg 的产生地。

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Hepatitis delta virus (hdv) replication through hbv integrants in hcc recurrence after liver transplantation

A PWID man, HCV/HBV-HDV/HIV-infected, underwent liver transplantation (LT) for HCC in 2012 at the age of 52 years. HCC tissue showed high HDV-RNA (88,400 copies/cell), low total HBV-DNA (0.00001 c/c), and HBVcccDNA0.00008 c/c), without detectable HBV-RNA. High-throughput HBV integration sequencing (HBIS) identified 657 HBV integration sites.HBV integrants were predominantly represented by HBx gene sequences. After LT, Tacrolimus, Bictegravir/Emtricitabine/TAF, and anti-HBs immunoglobulin were administered, yielding HBsAg, HDV-RNA, and HCV-RNA negativity.

In 2018, HBsAg reversion was observed with undetectable HBV-DNA and HDV-RNA >19,000 c/ml.

In 2019, HDV-related hepatitis occurred. Intrahepatic HBcAg, HBsAgHBV DNA, HBVcccDNA, and HBV-RNA were undetectable. HDV RNA concentrations were very high in the liver (3,920,000 c/c) but low in the serum (214 IU/mL). CT scan (CTs) suspected an isolated HCC recurrence in the left adrenal gland, confirmed by adrenalectomy. Real-time PCR in the tumor from the adrenal gland revealed high levels of HDV RNA (5.5 c/c) but low levels of HBV DNA (0.00009 c/c) and HBVcccDNA (0.00001 c/c). HBV RNA was undetectable. HBIS identified 3497 HBV integrations, most of which included HBs gene sequences. After adrenalectomy, HBsAg and HDV-RNA became undetectable. Anti-HBs immunoglobulin was continued with Everolimus.

In 2021, CTs showed two HCC nodules in the liver and one in the right adrenal gland. TACE was performed, and TKI therapy was started.

In 2023, new HDV hepatitis occurred, with HDV-RNA>3,631,360 UI/ml and HBV-DNA <10UI/ml. For the progression of HCC, RFA on the right adrenal gland was performed, and Bulevirtide was started. After 3 months, HDV-RNA was 48,638 c/ml, and transaminases were normal.

This case demonstrates HDV replication in extrahepatic HCC recurrence, despite low levels of HBVcccDNA. The decreased HDV RNA levels after RFA and BLV therapy suggest that HCC metastases may serve as HBsAg production sites following HBV integration.

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来源期刊

Digestive and Liver Disease 医学-胃肠肝病学

CiteScore

6.10

自引率

2.20%

发文量

632

审稿时长

19 days

期刊介绍： Digestive and Liver Disease is an international journal of Gastroenterology and Hepatology. It is the official journal of Italian Association for the Study of the Liver (AISF); Italian Association for the Study of the Pancreas (AISP); Italian Association for Digestive Endoscopy (SIED); Italian Association for Hospital Gastroenterologists and Digestive Endoscopists (AIGO); Italian Society of Gastroenterology (SIGE); Italian Society of Pediatric Gastroenterology and Hepatology (SIGENP) and Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Digestive and Liver Disease publishes papers on basic and clinical research in the field of gastroenterology and hepatology. Contributions consist of: Original Papers Correspondence to the Editor Editorials, Reviews and Special Articles Progress Reports Image of the Month Congress Proceedings Symposia and Mini-symposia.