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Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study. Seto Wai-Kay,Chan Thomas S Y,Hwang Yu-Yan,Wong Danny Ka-Ho,Fung James,Liu Kevin Sze-Hang,Gill Harinder,Lam Yuk-Fai,Lie Albert K W,Lai Ching-Lung,Kwong Yok-Lam,Yuen Man-Fung Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving rituximab-containing chemotherapy have not been well described. PATIENTS AND METHODS:HBsAg-negative, anti-HBc-positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered. RESULTS:Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients. CONCLUSION:A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs-negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications. 10.1200/JCO.2014.56.7081
Analysis of the immunity effects after enhanced hepatitis B vaccination on patients with lymphoma. Zhuang Wei-Huang,Wang Ya-Ping Leukemia & lymphoma The purpose of the study was to evaluate the immunity effects after vaccinating different doses and frequencies of hepatitis B vaccines by calculating the seroconversion rates of HBsAb in patients with lymphoma. Clinical data of 315 patients from January 2010 to August 2018 were analyzed. According to different doses and frequencies, the patients were divided into three groups: low-dose group, high-dose group, and high-dose and high-frequency group. The highest seroconversion rate of HBsAb was 82.3% in the high-dose and high-frequency group ( < .05). Multivariate logistic regression analysis showed that the dose and frequency of vaccination ( < .001, OR = 2.663), sex ( < .006, OR = 3.106), the Ann Arbor stage ( < .001, OR = 0.195) and whether the chemotherapy regimen contained ibrutinib or not ( < .008, OR = 8.115) are independent factors affecting the immunity effects of hepatitis B vaccine in patients with lymphoma. Increasing doses and frequencies of hepatitis B vaccination may improve the immune response in patients with lymphoma. 10.1080/10428194.2019.1672053
Treatment to prevent hepatitis B virus reactivation in patients with lymphoma receiving chemotherapy--reply. Lin Tongyu,Huang He,Li Xueying JAMA 10.1001/jama.2015.1444
Risk of all-type cancer, hepatocellular carcinoma, non-Hodgkin lymphoma and pancreatic cancer in patients infected with hepatitis B virus. Andersen E S,Omland L H,Jepsen P,Krarup H,Christensen P B,Obel N,Weis N, Journal of viral hepatitis The increased risk of hepatocellular carcinoma (HCC) among patients infected with hepatitis B virus (HBV) is well established; however, long-term risk estimates are needed. Recently, it has been suggested that HBV is associated with non-Hodgkin lymphoma (NHL) and pancreatic cancer (PC). The aim of this Danish nationwide cohort study was to evaluate the association between HBV infection and all-type cancer, HCC, NHL and PC. A cohort of patients infected with HBV (n = 4345) and an age- and sex-matched population-based comparison cohort of individuals (n = 26,070) without a positive test for HBV were linked to The Danish Cancer Registry to compare the risk of all-type cancer, HCC, NHL and PC among the two groups. The median observation period was 8.0 years. Overall, the incidence rate ratio (IRR) for all-type cancer among HBV-infected patients was 1.1 (95% confidence intervals (CI) 0.9-1.3). The IRR of HCC was 17.4 (CI 5.5-54.5), whereas the IRR of PC and NHL was 0.9 (CI 0.3-2.5) and 1.2 (CI 0.4-3.6), respectively. HBV-infected patients had a 10-year risk of 0.24% (Cl 0.12-0.44) for HCC, whereas the comparison cohort had a 10-year risk of 0.03% (Cl 0.02-0.07) for HCC. The risk of all-type cancer, NHL and PC was not higher in the HBV-infected cohort compared to non-HBV infected. We found a 17-fold higher risk of HCC for HBV-infected individuals. 10.1111/jvh.12391
Hepatitis B virus infection and risk of lymphoma: results of a serological analysis within the European case-control study Epilymph. Becker Nikolaus,Schnitzler Paul,Boffetta Paolo,Brennan Paul,Foretova Lenka,Maynadié Marc,Nieters Alexandra,Staines Anthony,Benavente Yolanda,Cocco Pierluigi,de Sanjose Silvia Journal of cancer research and clinical oncology BACKGROUND:We have recently reported from Epilymph, a multicentre case-control study of lymphoma conducted in six European countries, a significant association between NHL and self-reported history of past or present HBV infection based on questionnaire data from face-to-face interviews. METHODS:To corroborate this observation, we used the data and blood specimen from Epilymph to investigate the associations between serological indicators of HBV infection with risk of Hodgkin lymphoma, non-Hodgkin lymphoma (NHL) and specific lymphoma entities. For 1,518 cases and 1,496 controls with sufficient amount of serum or plasma, we tested HBs-antigen, anti-HBc and anti-HBs to distinguish between current or past infection and immunity by vaccination. Statistical analysis was carried out with unconditional logistic regression. RESULTS:We found a positive association of a past HBV infection with multiple myeloma (MM, OR = 1.97, 95 % CL = 1.16-3.37). Non-significant associations were found between past HBV infection and B-cell chronic lymphocytic leukaemia (B-CLL, OR = 1.33, 95 % CL = 0.82-2.16) and T-cell NHL (OR = 1.59, 95 % CL = 0.65-3.90), as well as between current HBV infection and NHL (OR = 1.49, 95 % CL = 0.65-3.41), B-NHL (OR = 1.58, 95 % CL = 0.69-3.64) and diffuse large B-cell lymphoma (DLBCL, OR = 1.50, 95 % CL = 0.47-4.82). Subjects having self-reported HBV infection were serological positive in 75 % of cases and 80 % of controls. For vaccination, the corresponding figures were 49 and 54 %, respectively. CONCLUSION:The present results support previous reports of an association between a history of HBV infection with an elevated lymphoma risk and add multiple myeloma to the list of potentially virus-associated lymphoma entities. 10.1007/s00432-012-1279-y
Hepatitis B virus screening before chemotherapy for lymphoma: a cost-effectiveness analysis. Zurawska Urszula,Hicks Lisa K,Woo Gloria,Bell Chaim M,Krahn Murray,Chan Kelvin K,Feld Jordan J Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:Hepatitis B virus (HBV) reactivation is a potentially fatal complication of chemotherapy that can be largely prevented with antiviral prophylaxis. It remains unclear whether HBV screening is cost effective. METHODS:A decision model was developed to compare the clinical outcomes, costs, and cost effectiveness of three HBV screening strategies for patients with lymphoma before R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy: screen all patients for hepatitis B surface antigen (HBsAg; Screen-All), screen patients identified as being at high risk for HBV infection (Screen-HR), and screen no one (Screen-None). Patients testing positive were administered antiviral therapy until 6 months after completion of chemotherapy. Those not screened were initiated on antiviral therapy only if HBV hepatitis occurred. Probabilities of HBV and lymphoma outcomes were derived from systematic literature review. A third-party payer perspective was adopted, costs were expressed in 2011 Canadian dollars, and a 1-year time horizon was used. RESULTS:Screen-All was the dominant strategy. It was least costly at $32,589, compared with $32,598 for Screen-HR and $32,657 for Screen-None. It was also associated with the highest 1-year survival rate at 84.99%, compared with 84.96% for Screen-HR and 84.86% for Screen-None. The analysis was sensitive to the prevalence of HBsAg positivity in the low-risk population, with Screen-HR becoming least costly when this value was ≤ 0.20%. CONCLUSION:In patients receiving R-CHOP for lymphoma, screening all patients for HBV reduces the rate of HBV reactivation (10-fold) and is less costly than screening only high-risk patients or screening no patients. 10.1200/JCO.2011.40.7510
Hepatitis B infection increases the risk of non-Hodgkin lymphoma: a meta-analysis of observational studies. Dalia Samir,Chavez Julio,Castillo Jorge J,Sokol Lubomir Leukemia research Hepatitis B virus (HBV) infection is a major public health problem and the association between HBV infection and non-Hodgkin lymphoma (NHL) is unclear. The primary aim of our study was to evaluate the association between HBV infection assessed by a positive hepatitis B surface antigen (HBsAg) and the incidence of NHL and subtypes using a meta-analysis of epidemiological studies. The random effects model was used to calculate the outcome. Our search yielded 17 case-control and 5 cohort studies, including over 40,000 NHL cases. HBV infected individuals had an OR of 2.24 (95% CI 1.80-2.78; p ≤ 0.001) of developing NHL. In high HBV prevalent countries, there were increased odds of diffuse large B-cell lymphoma and a trend toward increased odds of developing follicular and T-cell lymphoma. Future research is needed to better understand the biological mechanisms responsible for lymphomagenesis in patients with HBV infection. 10.1016/j.leukres.2013.06.007
Gene Rearrangements Are Closely Associated with Poor Survival of Diffuse Large B Cell Lymphoma with Hepatitis B Virus Infection. BioMed research international The aim of this study was to identify clinical adverse prognostic factors affecting overall survival (OS) of diffuse large B cell (DLBCL) patients with hepatitis B virus (HBV) infection. In this study, 30 DLBCL patients with HBV infection and 51 DLBCL patients with HBV-free were reviewed retrospectively. As of July 2016, the median follow-up period was 26.4 months (3.0~65.0 months). The median OS of patients in HBV infection group was 38.6 months, while that of patients in HBV-free group was not reached ( = 0.042); the median progression-free survival (PFS) of patients in HBV infection group was worse than that in HBV-free group, 18.5 months and 38.5 months ( = 0.118), respectively. The rate of and gene rearrangements in HBV infection group was significantly higher than that in HBV-free group, 20.0% versus 3.9% ( = 0.019) and 23.3% versus 5.9% ( = 0.021), respectively. Multivariable analysis indicated that IPI ( = 0.002), chemotherapy regimens ( = 0.017), and gene rearrangements ( = 0.004) were independent adverse prognostic factors for all DLBCL patients in this study. Results demonstrated that the poor survival of DLBCL patients with HBV infection was closely involved in chemotherapy regimens, IPI, and gene rearrangements. 10.1155/2017/1967648
Chemotherapy-induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: a prospective study. Hsu Chiun,Tsou Hsiao-Hui,Lin Shyh-Jer,Wang Ming-Chung,Yao Ming,Hwang Wen-Li,Kao Woei-Yau,Chiu Chang-Fang,Lin Sheng-Fung,Lin Johnson,Chang Cheng-Shyong,Tien Hwei-Fang,Liu Tsang-Wu,Chen Pei-Jer,Cheng Ann-Lii, Hepatology (Baltimore, Md.) UNLABELLED:Fatal hepatitis B virus (HBV) reactivation in lymphoma patients with "resolved" HBV infection (hepatitis B surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) can occur, but the true incidence and severity remain unclear. From June 2009 to December 2011, 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy were prospectively followed. HBV DNA was checked at baseline, at the start of each cycle of chemotherapy, and every 4 weeks for 1 year after completion of rituximab-CHOP chemotherapy. Patients with documented HBV reactivation were treated with entecavir at a dosage of 0.5 mg/day for 48 weeks. HBV reactivation was defined as a greater than 10-fold increase in HBV DNA, compared with previous nadir levels, and hepatitis flare was defined as a greater than 3-fold increase in alanine aminotransferase (ALT) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV-related hepatitis flares was 10.4 and 6.4 per 100 person-year, respectively. Severe HBV-related hepatitis (ALT >10-fold of upper limit of normal) occurred in 4 patients, despite entecavir treatment. Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation (100% vs. 28.5%; P=0.003). CONCLUSION:In lymphoma patients with resolved HBV infections, chemotherapy-induced HBV reactivation is not uncommon, but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy. Serological breakthrough (i.e., reappearance of HBsAg) is the most important predictor of HBV-related hepatitis flare. (Hepatology 2014;59:2092-2100). 10.1002/hep.26718
Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection. Yang Hung-Chih,Tsou Hsiao-Hui,Pei Sung-Nan,Chang Cheng-Shyong,Chen Jia-Hong,Yao Ming,Lin Shyh-Jer,Lin Johnson,Yuan Quan,Xia Ningshao,Liu Tsang-Wu,Chen Pei-Jer,Cheng Ann-Lii,Hsu Chiun, Journal of hepatology BACKGROUND & AIMS:Absence or low anti-HBV surface antibody (anti-HBs) is associated with an increased risk of HBV reactivation in patients with lymphoma and resolved HBV infection receiving rituximab-containing chemotherapy. Quantification of anti-HBV core antibody (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection. This study investigated whether baseline anti-HBc and anti-HBs levels may better predict HBV reactivation. METHODS:We prospectively measured the HBV DNA levels of patients with lymphoma and resolved HBV infection receiving rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone-based chemotherapy and started an antiviral therapy upon HBV reactivation, defined as a greater than 10-fold increase in HBV DNA compared with previous nadir levels. Anti-HBs and anti-HBc were quantified by a double-sandwich assay. Receiver-operating-characteristic-curve analysis was used to determine the optimal baseline anti-HBc/anti-HBs levels for predicting HBV reactivation. RESULTS:HBV reactivation occurred in 24 of the 197 patients enrolled, with an incidence of 11.6/100 person-years. For the 192 patients with enough serum samples for analysis, low anti-HBs (<56.48 mIU/ml) and high anti-HBc (≥6.41 IU/ml) at baseline were significantly associated with high risk of HBV reactivation (hazard ratio [HR] 8.48 and 4.52, respectively; p <0.01). The multivariate analysis indicated that (1) patients with both high anti-HBc and low anti-HBs at baseline (36 of 192 patients) had an HR of 17.29 for HBV reactivation (95% CI 3.92-76.30; p <0.001), and (2) HBV reactivation may be associated with inferior overall survival (HR 2.41; 95% CI 1.15-5.05; p = 0.02). CONCLUSIONS:Baseline anti-HBc/anti-HBs levels may predict HBV reactivation in these patients with lymphoma and help optimize prophylactic antiviral therapy for high-risk patients. LAY SUMMARY:In this study, we identified a subgroup of patients with lymphoma and resolved hepatitis B virus infection that had a high risk of hepatitis B virus reactivation after receiving rituximab-containing chemotherapy. These findings will help optimize a preventive strategy, especially in hepatitis B virus endemic regions with limited healthcare resources. Clinical trial number: NCT 00931229. 10.1016/j.jhep.2018.02.033
Hepatitis B and C virus infection and risk of lymphoid malignancies: A population-based cohort study (JPHC Study). Abe Sarah Krull,Inoue Manami,Sawada Norie,Iwasaki Motoki,Shimazu Taichi,Yamaji Taiki,Sasazuki Shizuka,Tanaka Yasuhito,Mizokami Masashi,Tsugane Shoichiro, Cancer epidemiology BACKGROUND:Several studies have assessed the association between hepatitis B virus (HBV) and hepatitis C virus (HCV) and non-Hodgkin's lymphoma. However, few studies are cohort by design, conducted within the Asian context and even fewer studies consider other lymphoid malignancies. The aim of this study was to assess the association between HBV and HCV and the risk of lymphoid malignancies among Japanese adults. MATERIALS AND METHODS:The Japan Public Health Center prospective-based Study Cohort II was initiated in 1993/1994. 20,360 subjects with available data on HBV and HCV infection status from blood samples were followed up until the end of 2010 for an average of 16 years. During 324,139 person-years, 120 newly diagnosed cases of lymphoid malignancies were identified. Cox proportional hazards models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95%CIs). RESULTS:Of 20,360 subjects, 508 were HBsAg positive, 11,035 were anti-HBc positive, and 1,129 subjects were anti-HCV positive at baseline. The presence of HBsAg was positively associated with malignant lymphoma, especially with non-Hodgkin's lymphoma (HR=3.56, 95%CI=1.37-9.18) and diffuse large B-cell lymphoma (HR=7.22, 95%CI=2.34-22.29). In contrast, no clear association was observed between the presence of anti-HBc and anti-HCV. CONCLUSION:In conclusion, HBsAg but not anti-HBc or anti-HCV was positively associated with malignant lymphoma, particularly non-Hodgkin's lymphoma and diffuse large B-cell lymphoma in Japanese adults. 10.1016/j.canep.2015.06.002
Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study. Wang Qing,De Luca Andrea,Smith Colette,Zangerle Robert,Sambatakou Helen,Bonnet Fabrice,Smit Colette,Schommers Philipp,Thornton Alicia,Berenguer Juan,Peters Lars,Spagnuolo Vincenzo,Ammassari Adriana,Antinori Andrea,Quiros-Roldan Eugenia,Mussini Cristina,Miro Jose M,Konopnicki Deborah,Fehr Jan,Campbell Maria A,Termote Monique,Bucher Heiner C, Annals of internal medicine Background:Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective:To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design:Cohort study. Setting:18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients:HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements:Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results:A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation:Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion:In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source:European Union Seventh Framework Programme. 10.7326/M16-0240
Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study. Kusumoto Shigeru,Tanaka Yasuhito,Suzuki Ritsuro,Watanabe Takashi,Nakata Masanobu,Takasaki Hirotaka,Fukushima Noriyasu,Fukushima Takuya,Moriuchi Yukiyoshi,Itoh Kuniaki,Nosaka Kisato,Choi Ilseung,Sawa Masashi,Okamoto Rumiko,Tsujimura Hideki,Uchida Toshiki,Suzuki Sachiko,Okamoto Masataka,Takahashi Tsutomu,Sugiura Isamu,Onishi Yasushi,Kohri Mika,Yoshida Shinichiro,Sakai Rika,Kojima Minoru,Takahashi Hiroyuki,Tomita Akihiro,Maruyama Dai,Atsuta Yoshiko,Tanaka Eiji,Suzuki Takayo,Kinoshita Tomohiro,Ogura Michinori,Mizokami Masashi,Ueda Ryuzo Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs). METHODS:We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥ 11 IU/mL. RESULTS:With a median HBV DNA follow-up of 562 days, HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5-12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P < .001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis. CONCLUSIONS:Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299). 10.1093/cid/civ344
Hepatitis B virus infection correlates with poor prognosis of extranodal natural killer/T cell lymphoma. Wang Liang,Wu-Xiao Zhi-jun,Chen Xiao-qin,Zhang Yu-jing,Lu Yue,Xia Zhong-jun Leukemia & lymphoma Studies have shown that hepatitis B virus (HBV) infection may play an important role in the lymphomagenesis of lymphoma, but no studies regarding the relationship between HBV infection and extranodal natural killer/T cell lymphoma (ENKTL) have been reported previously. One hundred and seven patients diagnosed with ENKTL were retrospectively reviewed. The hepatitis B surface antigen (HBsAg)-positive rate was 13.1%, and no significant correlation existed between HBV infection and clinical characteristics (p > 0.05). No significant difference existed in complete remission rate between HBsAg-positive and -negative groups (42.9% vs. 44.1%, p = 1.000). In a multivariate Cox regression model that included international prognostic index (IPI) score, induction chemotherapy regimen and HBsAg status, all these variables were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) (p < 0.05). In conclusion, the HBsAg-positive rate in ENKTL was similar to that of the normal population in a high HBV endemic area, and HBsAg-positive status was an independent prognostic factor for OS and PFS. 10.3109/10428194.2014.953146
Lymphocyte/monocyte ratio and cycles of rituximab-containing therapy are risk factors for hepatitis B virus reactivation in patients with diffuse large B-cell lymphoma and resolved hepatitis B. Wu Chia-Yun,Hsiao Liang-Tsai,Chiou Tzeon-Jye,Gau Jyh-Pyng,Liu Jin-Hwang,Yu Yuan-Bin,Wu Yi-Tsui,Liu Chia-Jen,Huang Yu-Chung,Hung Man-Hsin,Chen Po-Min,Huang Yi-Hsiang,Tzeng Cheng-Hwai Leukemia & lymphoma Reactivation of hepatitis B virus (HBV) following rituximab (R)-containing chemotherapy for lymphoma is a major concern, and risk factors remain to be defined. We enrolled 190 patients diagnosed with diffuse large B-cell lymphoma (DLBCL) and resolved hepatitis B, receiving first-line R-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based regimens. Twenty-seven patients (14.2%) developed HBV reactivation during a median follow-up of 23.6 months. Two independent risk factors were identified: cycles of rituximab>8 (hazard ratio [HR], 2.797; 95% confidence interval [CI], 1.184-6.612) and lymphocyte/monocyte ratio (LMR)<2.50 (HR, 2.733; 95% CI, 1.122-6.657). Two-year overall survival in patients with or without HBV reactivation was 53.8% vs. 77.6% (p=0.025). Regarding the negative impact on clinical outcome, patients at "super high risk" of HBV reactivation, including those receiving more than eight cycles of R and having low LMR at diagnosis, may warrant first priority for antiviral prophylaxis. 10.3109/10428194.2014.991922
The impact of hepatitis B virus infection and vaccination on the development of non-Hodgkin lymphoma. Huang C-E,Yang Y-H,Chen Y-Y,Chang J-J,Chen K-J,Lu C-H,Lee K-D,Chen P-C,Chen C-C Journal of viral hepatitis Hepatitis B virus (HBV) infection has been documented as a risk factor for non-Hodgkin lymphoma (NHL). However, there are few large cohort studies, and there is no report about the impact of HBV vaccination. We conducted this study to evaluate these issues. We used the nationwide cohort of the Taiwan National Health Insurance Research Database for 1997-2013. We compared the incidence and the risk of developing NHL and CD20 aggressive lymphoma between HBV and non-HBV cohorts. The hazard ratios (HRs) were computed using Cox proportional hazards models. We matched these two large cohorts to reconfirm the data. We also compared the incidence of NHL between cohorts born before and after the inception of universal HBV vaccination. We found that HBV infection increased the risk for developing NHL and CD20 aggressive lymphoma, with HRs of 4.14 and 5.52, with a higher incidence of 17.07 and 13.9 per 100 000 person-years, respectively, compared to the non-HBV cohort. The incidence of NHL in the cohort born in the era before universal HBV vaccination was higher with 1.85 per 100 000 person-years compared to 0.74 in the cohort born later aged younger than 20. Our study confirms that HBV confers a greater risk for developing NHL, especially CD20 aggressive lymphoma. The impact of HBV vaccination is protective against lymphoma development in the teenagers in an endemic area, but longer follow-up is needed for older age. 10.1111/jvh.12713
Risk of hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients with undetectable serum HBV DNA after treatment with rituximab for lymphoma: a meta-analysis. Tang Zilin,Li Xiaodong,Wu Shunquan,Liu Yan,Qiao Yan,Xu Dongping,Li Jin Hepatology international BACKGROUND:Hepatitis B surface antigen (HBsAg)-negative/hepatitis B core antibody (HBcAb)-positive patients with undetectable serum hepatitis B virus (HBV) DNA have experienced and resolved hepatitis B virus (HBV) infection. Lymphoma patients with resolved HBV infection have high risk of HBV reactivation when treated with robust immunosuppressive agents, but the reported rate varies extensively between different studies. This study aims to estimate the risk of HBV reactivation in HBsAg-negative/HBcAb-positive patients receiving rituximab-containing chemotherapy for lymphoma. METHODS:Databases were searched for papers published in English until 8 August 2016. The pooled risk of HBV reactivation was estimated using a random-effects model. RESULTS:Data from 15 studies were retrieved, including a total of 1312 HBsAg-negative/HBcAb-positive lymphoma patients treated with rituximab-containing chemotherapy. The results revealed HBV reactivation rate of 9.0 % [95 % confidence interval (CI) 0.05-0.15]. In subgroup analysis, the reactivation rates for prospective and retrospective studies were 17 % (I  = 87.3 %; 95 % 0.08-0.39, p < 0.001) and 7 % (I  = 43.1 %; 95 % CI 0.05-0.11, p = 0.07), respectively. CONCLUSIONS:This meta-analysis confirms a measurable and potentially substantial risk of HBV reactivation in HBsAg-negative/HBcAb-positive patients with rituximab treatment for lymphoma. Prophylactic use of anti-HBV agents should be seriously considered for such patients. 10.1007/s12072-017-9817-y
Chronic hepatitis B is associated with an increased risk of B-cell non-Hodgkin's lymphoma and multiple myeloma. Su Tung-Hung,Liu Chun-Jen,Tseng Tai-Chung,Chou Shih-Wan,Liu Chen-Hua,Yang Hung-Chih,Wu Shang-Ju,Chen Pei-Jer,Chen Ding-Shinn,Chen Chi-Ling,Kao Jia-Horng Alimentary pharmacology & therapeutics BACKGROUND:Chronic hepatitis B has been linked to lymphoma with contradictory results. AIM:To investigate the association between chronic hepatitis B and lymphoma by using a nationwide population-based cohort. METHODS:Records of patients diagnosed with chronic hepatitis B (hepatitis B virus [HBV] cohort) or without (non-HBV cohort) during 2004-2007 were retrieved from the Taiwan National Health Insurance Research Database. Age, sex, comorbidities, and medical visits were matched using propensity scores between both cohorts, and they were followed up longitudinally until 2012 to determine any new lymphoma development. RESULTS:A total of 203 031 patients were included in each cohort with a mean follow-up of 7-9 years. The lymphoma incidence rate was significantly higher in the HBV cohort than in the non-HBV cohort (29.4 vs 15.9 per 100 000 person-years, P < 0.0001). After adjustment for comorbidities and medical visits, HBV infection was found to be an independent risk factor associated with the development of lymphoma (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.76-2.43, P < 0.0001) and non-Hodgkin's lymphoma (HR: 2.18, 95% CI: 1.80-2.65, P < 0.0001); specifically with an increased risk of diffuse large B-cell lymphoma (HR: 2.69, 95% CI: 2.05-3.52, P < 0.0001), other B-cell lymphoma (HR: 3.11, 95% CI: 1.89-5.11, P < 0.0001), and also for multiple myeloma (HR: 1.63, 95% CI: 1.10-2.42, P = 0.016). The association was significant even after excluding lymphoma development within the first year (HR: 2.08, 95% CI: 1.75-2.47, P < 0.0001). CONCLUSIONS:Chronic hepatitis B is temporally associated with a 2-fold increased risk of lymphoma, particularly with B-cell non-Hodgkin's lymphoma, and also an increased risk for multiple myeloma. 10.1111/apt.15132