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      非霍奇金淋巴瘤合并HBV感染患者的临床特征及预后相关因素分析 Translated title: Analysis of clinical characteristics and prognostic factors in patients with non-Hodgkin lymphoma and HBV infection

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          Abstract

          目的

          探讨非霍奇金淋巴瘤(NHL)合并HBV感染患者的临床特征及预后相关因素,为临床精准诊治和预后评估提供依据。

          方法

          收集2012年8月至2016年7月313例初诊NHL患者资料,采用ELISA法检测患者HBV血清学标志物,采用全自动微粒子化学发光免疫分析法定量检测HBV DNA(≥1×10 5拷贝/ml为高拷贝组,1×10 3~<1×10 5拷贝/ml为低拷贝组),结合患者的临床特征,分析其HBV感染与预后的关系,并与普通人群HBV检出率(来源于全国HBV血清流行病学资料)进行对比。

          结果

          ①NHL患者组HBsAg阳性率为12.5%(39/313),高于普通人群的7.2%( χ 2=14.596, P<0.001);HBV既往感染者(HBsAg阴性但HBcAb阳性)114例(36.4%),发生率较普通人群(34.1%)略高。②HBsAg阳性组和阴性组比较,B细胞型(87.2%对70.3%, P=0.027)、Ann Arbor分期Ⅲ~Ⅳ期(69.2%对34.6%, P<0.001)、IPI评分3~5分(74.4%对50.0%, P=0.004)、LDH水平升高(79.5%对47.8%, P<0.001)、肝脏受累(45.5%对31.7%, P=0.006)患者的比例均较高,差异均有统计学意义。③HBV既往感染组(114例)与非感染组(160例)比较,Ann Arbor分期Ⅲ~Ⅳ期( P=0.023)、IPI评分3~5分( P=0.035)患者的比例组间差异均有统计学意义。④HBV DNA阳性组(30例)与阴性组(71例)比较,Ann Arbor分期Ⅲ~Ⅳ期( P=0.011)、IPI评分3~5分( P=0.03)、LDH水平升高( P=0.025)及肝脏受累( P<0.001)患者的比例组间差异均有统计学意义;以1×10 5拷贝/ml为界将30例阳性组患者划分为HBV DNA高拷贝组(23例)和低拷贝组(7例),结果显示两组患者的上述临床特征差异无统计学意义( P值均>0.05)。

          结论

          NHL患者的HBV感染率明显高于普通人群,HBV感染和B细胞型NHL关系更密切;合并HBV感染、HBV DNA阳性患者Ann Arbor分期晚、IPI评分高、LDH水平高、易发生肝脏受累,其预后偏差。

          Translated abstract

          Objective

          To explore the clinical characteristics and prognostic factors of the patients with non-Hodgkin's Lymphoma (NHL) complicated with HBV infection, so as to provide a basis for clinical accurate diagnosis and prognosis evaluation.

          Methods

          The data of 313 newly diagnosed NHL patients from August 2012 to July 2016 were collected. The HBV serological markers were detected by ELISA, and HBV DNA was quantified by full automatic microparticle chemiluminescence immunoassay (≥1×10 5 copies/ml as high copy group, 1×10 3–<1×10 5 copies/ml as low copy group). The relationship between HBV infection and prognosis was analyzed combined with the clinical features of the patients, and the HBV detection rate was compared with that of the common population (from the national HBV sero epidemiological data).

          Results

          ①The positive rate of HBsAg in NHL patients was 12.5% (39/313), which was higher than 7.2% in the general population ( χ 2=14.596, P<0.001). HBV infection in the past (HBsAg negative but HBcAb positive) in 114 cases (36.4%), the incidence was slightly higher than that in the general population (34.1%). ②Compared HBsAg positive group with the negative group, the proportion of B cell type (87.2% vs 70.3%, P=0.027), Ann Arbor stage Ⅲ–Ⅳ(69.2% vs 34.6%, P<0.001), IPI score 3–5 (74.4% vs 50%, P=0.004), LDH level (79.5% vs 47.8%, P<0.001) and liver involvement (45.5% vs 31.7%, P=0.006) were all higher. The difference was statistically significant. ③Compared the HBV infected group (114 cases) with the non-infected group (160 cases), the difference had statistical significance in the proportion of Ann Arbor stage Ⅲ–Ⅳ ( P=0.023) and IPI score 3–5 scores P=0.035). ④Compared HBV DNA positive group (30 cases) with negative group (71 cases), Ann Arbor stage Ⅲ–Ⅳ ( P=0.011), IPI score 3–5 score ( P=0.030), LDH level ( P=0.025) and liver involvement ( P<0.001) in the proportion of patients had statistical significance. The positive patients were divided into HBV DNA high and low copy groups with 1×10 5 copies of /ml as the boundary. The results showed that there was no statistical difference between the two groups ( P>0.05).

          Conclusion

          The HBV infection rate of NHL patients is significantly higher than that of the general population, and HBV infection is more closely related to B cell type NHL. Patients with HBV infection and HBV DNA positive had late Ann Arbor stage, high IPI score, high LDH level and liver involvement, and the prognosis is poor.

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          Most cited references21

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          Hepatitis B virus-associated diffuse large B-cell lymphoma: unique clinical features, poor outcome, and hepatitis B surface antigen-driven origin

          While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known more than this epidemiologic evidence. We studied a cohort of 587 patients with DLBCL for HBV infection status, clinicopathologic features, and the immunoglobulin variable region in HBV surface antigen (HBsAg)-positive patients. Eighty-one (81/587, 13.8%) patients were HBsAg-positive. Compared with HBsAg-negative DLBCL, HBsAg-positive DLBCL displayed a younger median onset age (45 vs. 55 years), more frequent involvement of spleen or retroperitoneal lymph node (40.7% vs. 16.0% and 61.7% vs. 31.0% respectively, both p < 0.001), more advanced disease (stage III/IV: 76.5% vs 59.5%, p = 0.003), and significantly worse outcome (2-year overall survival: 47% versus 70%, p < 0.001). In HBsAg-positive DLBCL patients, almost all (45/47, 96%) amino acid sequences of heavy and light chain complementarity determining region 3 exhibited a high homology to antibodies specific for HBsAg, and the majority (45/50, 90%) of IgHV and IgLV genes were mutated. We conclude that 13.8% of DLBCL cases are HBV-associated in HBV-endemic China and show unique clinical features and poor outcomes. Furthermore, our study strongly suggests that HBV-associated DLBCL might arise from HBV antigen-selected B cells.
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            High prevalence of hepatitis B virus infection in B-cell non-Hodgkin's lymphoma.

            In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.
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              Hepatitis B and C viruses and risk of non-Hodgkin lymphoma: a case-control study in Italy

              Background Hepatitis C virus (HCV) has been consistently associated to non-Hodgkin lymphoma (NHL); conversely, few studies have evaluated a comprehensive serological panel of hepatitis B virus (HBV) in NHL etiology. Methods We conducted a case-control study in Italy in 1999–2014, enrolling 571 incident, histologically confirmed NHLs and 1004 cancer-free matched controls. Study subjects provided serum for HCV and HBV testing and for HCV RNA. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were estimated by logistic regression, adjusting for potential confounders. Results Circulating HCV RNA was detected in 63 (11.1 %) NHL cases and 35 (3.5 %) controls (OR = 3.51, 95 % CI: 2.25–5.47). Chronic HBV infection (i.e., positive to HBV surface antigen - HBsAg+) was found in 3.7 % of cases and 1.7 % of controls (OR = 1.95, 95 % CI: 1.00–3.81); a significantly elevated OR was observed for B-cell NHL (2.11, 95 % CI: 1.07–4.15). People with serological evidence of past HCV or HBV infection, vaccination against HBV, or detectable antibodies against HBV core antigen (anti-HBc+) alone were not at increased NHL risk. Conclusions Our results support a role of chronic HCV infection in NHL in Italy and suggest an involvement of HBV infection. Associations were clearest for B-cell NHL and diffuse large B-cell lymphoma. Prevention and treatment of HCV and HBV infection may diminish NHL incidence, notably in areas with high prevalence of hepatitis viruses infection.
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                Author and article information

                Journal
                Zhonghua Xue Ye Xue Za Zhi
                Zhonghua Xue Ye Xue Za Zhi
                CJH
                Chinese Journal of Hematology
                Editorial office of Chinese Journal of Hematology (No. 288, Nanjing road, Heping district, Tianjin )
                0253-2727
                2707-9740
                July 2018
                : 39
                : 7
                : 563-568
                Affiliations
                [1]450003 郑州,河南省人民医院血液病研究所Institute of Hematology of Henan People's Hospital, Zhengzhou 450003, China
                Author notes

                张令(锦州医科大学在读研究生)

                通信作者:朱尊民(Zhu Zunmin),Email: zhuzm1964@ 123456163.com
                Article
                cjh-39-07-563
                10.3760/cma.j.issn.0253-2727.2018.07.007
                7342218
                30122015
                dcc26e72-735b-43c8-b2f3-6ea8e4c58b00
                2018年版权归中华医学会所有Copyright © 2018 by Chinese Medical Association

                This work is licensed under a Creative Commons Attribution 3.0 License (CC-BY-NC). The Copyright own by Publisher. Without authorization, shall not reprint, except this publication article, shall not use this publication format design. Unless otherwise stated, all articles published in this journal do not represent the views of the Chinese Medical Association or the editorial board of this journal.

                History
                : 24 January 2018
                Funding
                基金项目:河南省卫计委科技攻关项目(2011020144)
                Fund Program: Science and Technology Tackling Project of Henan Provincial Health Planning Commission(2011020144)
                Categories
                论著

                淋巴瘤,非霍奇金,乙型肝炎病毒,lymphoma, non-hodgkin's,hepatitis b virus

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