entecavir and Lymphoma

Background Multiple studies have compared the efficacy of entecavir with lamivudine in preventing hepatitis B virus (HBV) reactivation among HBV-carrying lymphoma patients with chemotherapy treatment. However, the results were slightly varied. Aim of the review to combine the findings of independent studies assessing the clinical efficacy of the two drugs using a systematic review and meta-analysis. Methods PubMed, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chongqing VIP and WanFang Data were retrieved. Two independent reviewers evaluated the study eligibility and extracted eight studies, with 770 patients in total. The meta-analysis was conducted using RevMan 5.3 and STATA software. Results HBV-carrying lymphoma patients receiving lamivudine during chemotherapy had a statistically significantly higher odds of HBV reactivation compared to those receiving entecavir (OR 5.0, 95 % CI 2.85-8.78, P < 0.001). The odds of hepatitis, HBV-Reactivation caused hepatitis and chemotherapy disruption was statistically significantly elevated in the patient group receiving lamivudine compared to the entecavir group (OR 4.12, 95 % CI 1.70-9.98, P = 0.002; OR 11.44, 95 % CI 2.70-48.52, P < 0.001; OR 6.71, 95 % CI 2.34-19.26, P < 0.001, respectively). Furthermore, the HBV reactivation rate in Ann Arbor stages I - II patient group was statistically significantly lower than the one in Ann Arbor stages III-IV group, with an overall pooled value of 0.37 (95 % CI 0.17-0.82, P = 0.01). Conclusion The metaanalysis result suggested that among HBV-carrying lymphoma patients undergoing chemotherapy, entecavir is more effective than lamivudine in preventing HBV reactivation.

Topics: Antineoplastic Agents; Antiviral Agents; Guanine; Hepatitis B; Hepatitis B virus; Humans; Lamivudine; Lymphoma; Treatment Outcome

The value of prophylactic antiviral therapy in patients with past hepatitis B virus (HBV) infection (HBV surface antigen-negative/anti-HBV core antibody-positive/HBV DNA negative) is still controversial.. This study compared the safety, efficacy, and cost-effectiveness of prophylactic entecavir (ETV) with regular monitoring alone in lymphoma patients with past HBV infection. Patients were randomly assigned to chemotherapy alone (control) or prophylactic ETV before chemotherapy and at least 6 months after completion of chemotherapy. All patients underwent close virologic and biochemical surveillance. The primary end points were the incidence rates of HBV reactivation (appearance of HBV DNA) and HBV reactivation-related hepatitis (defined as a greater than 3-fold increase in serum alanine aminotransferase levels exceeding 100 IU/L).. A total of 190 patients were included, 141 (74.2%) of whom were positive for anti-HBV surface antibody (HBs). The incidence rates of HBV reactivation and HBV reactivation-related hepatitis were 0 (0/95) and 0 (0/95) in the prophylactic ETV group, respectively, and 3.2% (3/95) and 1.1% (1/95) in the control group, respectively (P = .246 and 1.000, respectively). One patient experienced HBV reactivation-related hepatitis, resulting in premature termination of chemotherapy. All 3 patients with HBV reactivation recovered after therapeutic ETV treatment. No HBV-related deaths were observed during the follow-up period. The cost in the prophylactic ETV group was higher than that in the control group ($125 per month).. Prophylactic antiviral therapy is not a cost-effective strategy for the management of lymphoma patients with past HBV infection, especially those positive for anti-HBs.

Topics: Adolescent; Adult; Antiviral Agents; Child; Child, Preschool; Female; Guanine; Hepatitis B; Humans; Infant; Lymphoma; Male; Middle Aged; Young Adult

The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear.. Eighty patients with CD20(+) lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39).. Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion.. Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antineoplastic Agents; Antiviral Agents; DNA, Viral; Female; Guanine; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Lymphoma; Male; Middle Aged; Rituximab; Virus Activation

During chemotherapy for lymphoma, the administration of cytotoxic agents and rituximab often results in hepatitis B reactivation (incidence, 14-72%). This study was designed to compare the efficacy of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients. Between January 2007 and February 2009, patients treated in four hospitals in China were screened to identify those most appropriate for analysis. These patients received either entecavir or lamivudine during chemotherapy and for 6 months after completion of chemotherapy. A total of 34 patients received entecavir and 89 patients received lamivudine. Compared with the lamivudine group, the entecavir group had significantly lower rates of hepatitis (5.9 vs 27.0%, P = 0.007), hepatitis B reactivation (0 vs 12.4%, P = 0.024) and disruption of chemotherapy (5.9 vs 20.2%, P = 0.042). All patients with hepatitis B reactivation had B-cell non-Hodgkin's lymphoma (stage III-IV). In lymphoma patients under chemotherapy treatment, entecavir is more effective than lamivudine in preventing hepatitis B reactivation. For patients with advanced stage disease, entecavir should be considered the primary preventive therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antiviral Agents; Chemoprevention; China; Female; Guanine; Hepatitis B; Humans; Lamivudine; Lymphoma; Male; Middle Aged; Treatment Outcome; Virus Activation; Young Adult

To investigate the efficacy of nucleosides as a prophylactic agent against reactivation of hepatitis B virus (HBV) in HBsAg-positive patients with non-hepatic tumors after chemotherapy.. Fifty-eight patients with non-hepatic tumors were divided into prevention group and control group. The patients of prevention group received nucleosides as a prophylactic agent before chemotherapy and were compared with the control ones about the clinical manifestation of HBV reactivation. Then, the patients of the control group were divided into three groups according to antiviral drugs, use or not and time of the use. The patients having HBV reactivation but never received nucleosides were included in the group A, the patients receiving nucleosides after having HBV reactivation were divided into the group B, and the patients receiving nucleosides before HBV reactivation were divided into the group C. The progression, prognosis and curative effect among the three groups were compared.. The rate of HBV reactivation, incidence of severe hepatitis, mortality rate of the control group (61.1%, 27.8%, 16.7%) were significantly higher than those of the prevention group (13.6%, 0, 0), and liver dysfunction was more serious than that in the prevention group. In the control group, all the 5 patients of group A died of liver failure. Of the 13 patients in the group B, 4 cases suffered from severe hepatitis and 1 of them died of the disease. Of the 18 patients in the group C, 4 cases suffered from HBV reactivation, but the clinical manifestation was milder than that of the group B.. Nucleosides can be used as a prophylactic measure to prevent HBV reactivation. If chemotherapy had begun, the use of nucleosides may reduce the risk of HBV reactivation. Even if patients had suffered from HBV reactivation, the use of nucleosides may still help the recovery of liver function and improve prognosis.

Topics: Adult; Antineoplastic Agents; Antiviral Agents; Breast Neoplasms; Female; Follow-Up Studies; Guanine; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Lamivudine; Lung Neoplasms; Lymphoma; Male; Middle Aged; Nucleosides; Pyrimidinones; Retrospective Studies; Telbivudine; Thymidine; Virus Activation

Hepatitis B virus (HBV) reactivation is a common complication in chronic or resolved HBV infection patients undergoing immunosuppressive chemotherapy. Furthermore, few articles have been published regarding the risk of HBV reactivation in lymphoma patients receiving chimeric antigen receptor (CAR) T-cell therapy and anti-HBV prophylaxis. Few guidelines or clear optimal strategies are available for managing these patients. Here, we present two cases of patients who underwent CAR-T-cell cocktail therapy with anti-CD19 and anti-CD22 CAR (CAR19/22) T cell for lymphoma. Patients had previous history of HBV infection, and blood tests on initial admission indicated positive results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and antibody to hepatitis B e antigen (anti-HBe), while serum HBV DNA level was undetectable. Therefore, two patients received entecavir as antiviral prophylactic therapy during their entire treatment. They were diagnosed with HBV reactivation based on positive serum HBV DNA test results, 2 weeks after CAR-T-cell infusion. Liver function assay indicated elevated levels of alanine transaminase (ALT) and aspartate transaminase (AST), combined with increased levels of total bilirubin (TBIL) and direct bilirubin (DBIL). Subsequently, they received anti-HBV treatment with entecavir and tenofovir. As a result, their serum HBV DNA copies and AST/ALT levels returned to normal after 1 week. These cases show that there is a risk of HBV reactivation in lymphoma patients with CAR-T-cell therapy despite entecavir preventive therapy, and combination treatment of entecavir and tenofovir may be an effective treatment option for such patients with HBV reactivation.

Topics: Antiviral Agents; Female; Guanine; Hepatitis B; Hepatitis B virus; Humans; Immunotherapy, Adoptive; Infusions, Intravenous; Latent Infection; Lymphoma; Male; Middle Aged; Receptors, Chimeric Antigen; Treatment Failure

A 68-year-old man with occult hepatitis B virus (HBV) infection was diagnosed with malignant lymphoma and achieved complete remission after treatment with a chemotherapy regimen including rituximab for 5 months. Entecavir (ETV) was also used during and after chemotherapy and was ended at 14 months after chemotherapy. However, reactivation of HBV was observed in blood tests, which showed not only elevation of HBV-DNA but also HBsAg and HBeAg, at 27 months after the end of chemotherapy. After restarting ETV, the HBV-DNA levels immediately subsided. In addition, anti-HBs became and remained positive at 31 months after chemotherapy. ETV was re-discontinued at 36 months after chemotherapy.

Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antiviral Agents; Guanine; Hepatitis B; Hepatitis B Antibodies; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Lymphoma; Male; Rituximab; Virus Activation

Tumor chemotherapy could weaken the immune system of patients, which might enhance the body sensitivities to the exogenous pathogens, among which the hepatitis B virus (HBV) infection should be concerned because of the higher chances of infection and the severe outcomes, especially in East Asia. The titer level of hepatitis B surface antibody (HBsAb) higher than 10 IU/L is considered to offer immunocompetent individuals adequate protection. However, whether this level is enough to the tumor patients during chemotherapy remains unclear.. A 58-year-old female lymphoma patient was admitted to our hospital for asthenia, nausea, vomiting, and abnormal liver function lasting over 1 week and diagnosed as acute hepatitis B. The patient just finished a course of chemotherapy with CHOP regimen and had recent record (78.61 IU/L) of HBsAb positive. The only risk of infection we could found was that the patient had received blood transfusion shortly after chemotherapy from a donor who was recovering from an asymptomatic acute HBV infection.. The patient was administered with entecavir and glycyrrhizic acid agent, and then the disease was resolved successfully with hepatitis B surface antigen serological conversion.. Tumor chemotherapy might have weakened the immune system of the patient and enhanced the body sensitivities to hepatitis B virus, then led to the infection. We concluded that HBsAb-positive status, at least "weakly positive," might not enough to provide protection for tumor patients on chemotherapy though this level was enough for health individuals and donors recuperating from subclinical acute hepatitis B might be another potential risk of HBV infection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Cyclophosphamide; Doxorubicin; Female; Guanine; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Lymphoma; Middle Aged; Prednisolone; Transfusion Reaction; Vincristine

Although antiviral prophylaxis is essential in hepatitis B patients in the context of cancer chemotherapy, there is little evidence-based consensus regarding the appropriate prevention strategy depending on the underlying type of cancer and viral status. This retrospective study included a comprehensive cohort of 302 hepatitis B surface antigen-positive patients with various cancers undergoing chemotherapy and antiviral prophylaxis. The rates of hepatitis B virus (HBV) reactivation during antiviral therapy (>1 log10 IU/mL increase or positive conversion of serum HBV DNA) and relapse when off antivirals ([re]appearance of HBV DNA >2,000 IU/ml with related alanine aminotransferase elevation) were evaluated, together with the associated risk factors, in a competing risks analysis where cancer death was considered as the competing event. During antiviral prophylaxis, HBV was reactivated in six patients (1.9%), who had leukemia (n = 4) or lymphoma (n = 2) and were treated with lamivudine (n = 4) or entecavir (n = 2). The incidence rate of HBV relapse in 127 off-prophylaxis patients was 21.3% during a median post-antiviral period of 11.7 months. Lymphoma, pre-prophylactic HBV DNA ≥2,000 IU/ml, and age ≥50 years were independent predictors of off-treatment HBV relapse (adjusted hazard ratios 5.25, 3.07, and 0.34, respectively; Ps < 0.05). Antiviral and anticancer drugs, duration of consolidation on antiviral prophylaxis, and HBeAg positivity were not independent predictors. In conclusion, hepatitis B flare-ups are not rare in patients receiving cancer chemotherapy during and after anti-HBV prophylaxis, even when potent antivirals are used. Patients with hematopoietic or lymphoid neoplasms or high viral burdens should receive prolonged and powerful HBV prophylaxis. J. Med. Virol. 88:1576-1586, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Adult; Alanine Transaminase; Antineoplastic Agents; Antiviral Agents; DNA, Viral; Female; Guanine; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Lymphoma; Male; Middle Aged; Neoplasms; Retrospective Studies; Risk Assessment; Viral Load; Virus Activation

Topics: Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antineoplastic Agents; Antiviral Agents; DNA, Viral; Guanine; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Lymphoma; Rituximab; Treatment Outcome; Virus Activation

OBJECTIVE. To serially evaluate the viral kinetics of occult hepatitis B virus infection in lymphoma patients and perform a correlation with clinical outcomes. DESIGN. Case series with 1-year follow-up. SETTING. Regional hospital, Hong Kong. PATIENTS. Consecutive patients who were newly diagnosed to have lymphoma in the hospital between 1 April 2007 and 31 March 2008 were tested for hepatitis B (HB) surface (s) antigen (Ag), anti-HBs antibody (Ab) and anti-HB core (c) Ab. Seropositive occult hepatitis B patients as defined by being negative for HBsAg but positive anti-HBsAb and/or anti-HBcAb without a hepatitis B vaccination history were recruited. Serum HBsAg, anti-HBsAb, anti-HBcAb, hepatitis B virus deoxyribonucleic acid (DNA) level, and liver biochemistry were checked at baseline and every 4 weeks during and after chemotherapy until 12 months after the completion of chemotherapy or death. Entecavir was started if patients developed biochemical flare-up of hepatitis B associated with virological rebound. The prevalence and course of hepatitis B virus-related hepatitis, as well as any temporal relationship to viral kinetics and clinical hepatitis, were assessed. RESULTS. Of 47 patients tested, 10 (21%) with lymphoma were seropositive occult hepatitis carriers. Their median baseline hepatitis B virus DNA level was 89 IU/mL (range, <34-807 IU/mL). Virological rebound (as defined by a 10-fold increase in serum hepatitis B virus DNA level from pre-chemotherapy level persisted for 4 weeks) occurred in one of the 10 patients, followed by biochemical reactivation. Whereupon entecavir treatment was started and no liver failure ensued. Regarding the other seropositive occult patients, their serum hepatitis B virus DNA levels fluctuated, but there was no associated biochemical reactivation. CONCLUSION. Detectable baseline serum hepatitis B virus DNA is not uncommon in patients with occult hepatitis B who receive chemotherapy. Transient elevation in serum hepatitis B virus DNA levels does not predict biochemical reactivation, but antiviral treatment might be considered if virological rebound persists.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Carrier State; Cyclophosphamide; DNA, Viral; Epirubicin; Female; Guanine; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Core Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Liver Function Tests; Lymphoma; Male; Middle Aged; Prednisolone; Prospective Studies; Rituximab; Time Factors; Vincristine; Viral Load

Topics: Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Chemoprevention; Cyclophosphamide; Doxorubicin; Female; Guanine; Hepatitis B; Hepatitis B virus; Humans; Lymphoma; Male; Middle Aged; Prednisone; Treatment Outcome; Vincristine; Virus Activation

Topics: Antiviral Agents; Guanine; Hepatitis B virus; Humans; Lymphoma; Male; Middle Aged; Virus Activation