Zhang Wenjing, Du Fan, Wang Li, Bai Tao, Zhou Xiang, Mei Heng
Department of Hematology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Clin Transl Hepatol. 2023 Oct 28;11(5):1256-1266. doi: 10.14218/JCTH.2022.00079S. Epub 2023 May 30.
Over the last decade, epidemiological studies have discovered a link between hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). The regression of HCV-associated NHL after HCV eradication is the most compelling proof supporting HCV infection's role in lymphoproliferative diseases. HBV infection was found to significantly enhance the incidence of NHL, according to the epidemiological data. The exact mechanism of HCV leading to NHL has not been fully clarified, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HCV and cytokines; (2) Direct mechanisms: oncogenic effects mediated by intracellular HCV proteins; (3) hit-and-run mechanism: permanent genetic B lymphocytes damage by the transitional entry of HCV. The specific role of HBV in the occurrence of NHL is still unclear, and the research on its mechanism is less extensively explored than HCV, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HBV; (2) Direct mechanisms: oncogenic effects mediated by intracellular HBV DNA. In fact, it is reasonable to consider direct-acting antivirals (DAAs) as first-line therapy for indolent HCV-associated B-NHL patients who do not require immediate chemotherapy. Chemotherapy for NHL is affected by HBV infection and replication. At the same time, chemotherapy can also activate HBV replication. Following recent guidelines, all patients with HBsAg positive/HBV DNA≥2,000 IU/mL should be treated for HBV. The data on epidemiology, interventional studies, and molecular mechanisms of HCV and HBV-associated B-NHL are systematically summarized in this review.
在过去十年中，流行病学研究发现丙型肝炎病毒（HCV）和乙型肝炎病毒（HBV）感染与非霍奇金淋巴瘤（NHL）之间存在关联。HCV根除后HCV相关NHL的消退是支持HCV感染在淋巴增殖性疾病中作用的最有说服力的证据。根据流行病学数据，发现HBV感染会显著提高NHL的发病率。HCV导致NHL的确切机制尚未完全阐明，主要有以下几种可能机制：（1）间接机制：细胞外HCV和细胞因子对B淋巴细胞的刺激；（2）直接机制：细胞内HCV蛋白介导的致癌作用；（3）打了就跑机制：HCV的过渡性进入对B淋巴细胞造成永久性基因损伤。HBV在NHL发生中的具体作用仍不清楚，对其机制的研究不如HCV广泛，主要有以下几种可能机制：（1）间接机制：细胞外HBV对B淋巴细胞的刺激；（2）直接机制：细胞内HBV DNA介导的致癌作用。事实上，对于不需要立即化疗的惰性HCV相关B-NHL患者，将直接抗病毒药物（DAAs）视为一线治疗是合理有效的。NHL的化疗会受到HBV感染和复制的影响。同时，化疗也可激活HBV复制。根据最新指南，所有HBsAg阳性/HBV DNA≥2000 IU/mL的患者均应接受HBV治疗。本文系统总结了HCV和HBV相关B-NHL的流行病学、干预性研究及分子机制方面的数据。
