乙型肝炎病毒相关性B细胞非霍奇金淋巴瘤的发生率及其临床特点的初步探讨

A preliminary investigation on the incidence of HBV-associated B-NHL and its clinical characteristics

摘要:

目的 了解乙型肝炎病毒（hepatitis B virus，HBV）感染对B细胞非霍奇金淋巴瘤（B-cell non-Hodgkin's lymphoma，B-NHL）发生和临床特点的影响。方法 对照分析非霍奇金淋巴瘤（non-Hodgkin's lymphoma，NHL）患者中乙型肝炎病毒表面抗原（hapatitis bsurface antigen，HBsAg）的携带率及HBV感染状态，比较不同类型B-NHL患者HBsAg阳性率差异及HBsAg阳性弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma，DLBCL）与HBsAg 阴性DLBCL的临床特征、化疗反应和2年生存率。结果 共纳入597例NHL患者为NHL组，其中B-NHL 461例，T细胞非霍奇金淋巴瘤103例。B-NHL患者HBV感染率（17.1%）明显高于对照组（5.7%），差异有统计学意义（P=0.003）。T细胞非霍奇金淋巴瘤患者HBsAg阳性率（10.7%）与对照组（5.7%）无统计学差异（P=0.796）。对影响351例DLBCL患者总生存率的单因素分析结果显示，女性、年龄≥60岁、HBsAg阳性、肝功能异常、血清乳酸脱氢酶（lactate dehydrogenase，LDH）升高、Ann Arbor期Ⅲ~Ⅳ期以及国际预后指数（international prognostic index，IPI）评分3~5分是不利因素（均Ｐ<0.05），而获得缓解是有利因素。Cox 回归分析显示患者年龄、HBsAg状态、Ann Arbor分期、治疗反应是影响患者预后的独立危险因素。与HBsAg阴性DLBCL比较，HBsAg阳性DLBCL患者发病年龄更轻（P=0.017），IPI评分较高（P=0.036）、Ann Arbor分期较晚（P=0.001）。HBsAg阳性DLBCL患者化疗有效率（完全缓解+部分缓解）和2年生存率显著低于HBsAg阴性DLBCL患者（P=0.026，P=0.031）。但2组乳酸脱氢酶升高率和脾脏受累率无显著差异。结论 HBsAg阳性患者可能有更高的风险患B-NHL，且HBV可能对B-NHL的临床特征和预后有负面影响。HBV不仅增加B-NHL的风险，还可加重病情，降低化疗效果，影响患者的远期预后。

Abstract:

Objective To investigate the prevalence of HBsAg in B-cell non-Hodgkin’s lymphoma（B-NHL） and the effect of hepatitis B virus（HBV） infection on the clinical features of B-NHL.Methods The carrier rate of hapatitis bsurface antigen（HBsAg） and hepatitis B infection status in patients with non-Hodgkin’s lymphoma（NHL） were analyzed，and the differences in HBsAg positivity rate and HBsAg positive diffuse large B-cell lymphoma（DLBCL），chemotherapy response and 2-year survival rate of HBsAg positive DLBCL and HBsAg negative DLBCL were compared.Results A total of 597 eligible NHL patients were enrolled as the NHL group，including 461 B-NHL patients and 103 T-cell non-Hodgkin’s lymphoma（T-NHL） patients. HBV infection rate in B-NHL patients（17.1%） was significantly higher than that in the control group（5.7%）（P=0.003）. However，there was no significant difference in the HBsAg positive rates of T-NHL patients（10.7%） as compared with the control group（5.7%）（P=0.796）. Univariate analysis of the overall survival rate of 351 DLBCL patients showed that female，≥ 60 years old，HBsAg positive，abnormal liver function， elevated serum lactate dehydrogenase（LDH），Ann Arbor stage III–IV and International Prognostic Index（IPI） scores of 3–5 were unfavorable factors（all P<0.05），while remission was a favorable factor. Cox regression analysis showed that patient age，HBsAg status，Ann Arbor stage， and response to treatment were independent risk factors affecting patient prognosis. Compared with HBsAg negative DLBCL，HBsAg positive DLBCL patients were younger at onset（P=0.017）， with higher IPI scores（P=0.036），and at later Ann Arbor stage（P=0.001）. The effective rate of chemotherapy（complete remission + partial remission） and the 2-year survival rate of patients with HBsAg positive DLBCL were significantly lower than those of patients with HBsAg negative DLBCL（P=0.026，P=0.031）. However，there were no significant differences in LDH elevation rate and spleen involvement rate between the two groups.Conclusion HBsAg positive patients may be at higher risk for B-NHL，and HBV may negatively affect the clinical features and prognosis of B-NHL. HBV not only increases the risk of B-NHL，but also aggravates the disease， reduces the effect of chemotherapy， and affects the long-term prognosis of patients.