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直接作用抗病毒药物治疗后成功的丙型肝炎病毒复发,随后发生肝细胞癌肉瘤样改变:一例报告。

Hepatitis C virus relapse after successful treatment with direct-acting antivirals, followed by sarcomatous changes in hepatocellular carcinoma: a case report.

机构信息

Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan.

Department of Pathology, Mitsui Memorial Hospital, Tokyo, Japan.

出版信息

J Med Case Rep. 2020 May 27;14(1):62. doi: 10.1186/s13256-020-02392-y.

Abstract

BACKGROUND

Combination therapy of interferon and ribavirin has traditionally been used to eradicate hepatitis C virus. The sustained virologic response achieved with interferon-related therapy is persistent, and late relapses after achieving sustained virologic response at 24 weeks using this therapy are reportedly rare (< 1%). In 2014, interferon-free therapy with direct-acting antivirals was developed, and the rate of sustained virologic response was improved. However, the persistence thereof remains uncertain, and the appropriate follow-up period for hepatitis C virus-positive patients is under discussion.

CASE PRESENTATION

A 74-year-old Japanese man who had hepatitis C virus-related hepatocellular carcinoma and was successfully treated with radiofrequency ablation four times underwent direct-acting antiviral therapy with daclatasvir and asunaprevir; sustained virologic response at 24 weeks was confirmed. However, although he had no high risk factors for reinfection, hepatitis C virus ribonucleic acid was detected again 6 months after achieving sustained virologic response at 24 weeks. Moreover, he developed active hepatitis with an increased viral load. Five months after development of hepatitis, recurrent hepatocellular carcinoma emerged in segment II, where we had performed radiofrequency ablation 17 months previously. The recurrent hepatocellular carcinoma enlarged quite rapidly and induced multiple peritoneal disseminations and lung metastases. He died 3 months after the abrupt recurrence. A sarcomatous change in the hepatocellular carcinoma was identified during the autopsy.

CONCLUSIONS

Although sustained virologic response at 24 weeks has generally been regarded to denote complete eradication of hepatitis C virus, we present a patient in whom hepatitis C virus recurred 6 months after achieving sustained virologic response at 24 weeks with direct-acting antiviral therapy. In addition, a sarcomatous change in hepatocellular carcinoma emerged 5 months after active hepatitis developed due to late hepatitis C virus relapse in this case. The sarcomatous change in hepatocellular carcinoma is generally thought to be related to anticancer therapies, such as radiofrequency ablation. However, in this case, late viral relapse and active hepatitis in addition to the previous radiofrequency ablation could have been the trigger. There may be a need for follow-up of hepatitis C virus ribonucleic acid beyond sustained virologic response at 24 weeks with direct-acting antiviral therapy, owing to the possibility of late viral relapse and tumorigenesis.

摘要

背景

干扰素和利巴韦林的联合治疗传统上用于清除丙型肝炎病毒。用干扰素相关疗法获得的持续病毒学应答是持久的,据报道,用这种疗法在 24 周时达到持续病毒学应答后,晚期复发很少见(<1%)。2014 年,开发了无干扰素的直接作用抗病毒药物治疗,提高了持续病毒学应答率。然而,其持久性仍不确定,丙型肝炎病毒阳性患者的适当随访期仍在讨论中。

病例介绍

一名 74 岁日本男性患有丙型肝炎病毒相关肝细胞癌,曾成功接受 4 次射频消融治疗,随后接受达卡他韦和asunaprevir 的直接作用抗病毒治疗;在 24 周时确认达到持续病毒学应答。然而,尽管他没有再感染的高危因素,但在达到 24 周持续病毒学应答后 6 个月再次检测到丙型肝炎病毒核糖核酸。此外,他出现了活性肝炎,病毒载量增加。在肝炎发生 5 个月后,在我们 17 个月前进行射频消融的 II 段出现了复发性肝细胞癌。复发性肝细胞癌迅速增大,并导致多个腹膜播散和肺转移。在突然复发后 3 个月他死亡。尸检时发现肝细胞癌有肉瘤样改变。

结论

虽然 24 周时的持续病毒学应答通常被认为表示丙型肝炎病毒的完全清除,但我们报告了一名患者,在接受直接作用抗病毒治疗后,在达到 24 周持续病毒学应答后 6 个月丙型肝炎病毒复发。此外,在本例中,由于丙型肝炎病毒的晚期复发导致活动性肝炎发生后 5 个月,出现了肝细胞癌的肉瘤样改变。肝细胞癌的肉瘤样改变通常被认为与射频消融等抗癌治疗有关。然而,在本例中,除了以前的射频消融之外,晚期病毒复发和活动性肝炎可能是触发因素。由于可能存在晚期病毒复发和肿瘤发生的可能性,用直接作用抗病毒治疗达到 24 周持续病毒学应答后,可能需要对丙型肝炎病毒核糖核酸进行随访。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b1a/7251811/48a53b58f588/13256_2020_2392_Fig1_HTML.jpg

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