Prophylactic Use Of Lamivudine Research Articles

Prophylactic Lamivudine to Improve the Outcome of Breast Cancer Patients With HBsAg Positive During Chemotherapy: A Meta-Analysis

ContextRaising the chemotherapy-induced HBV reactivation is parallel to the increment of chemotherapy treatments in breast cancer patients. This meta-analysis aims to evaluate the efficacy of prophylactic use of lamivudine in breast cancer patients with HBsAg positive during chemotherapy.Evidence AcquisitionMEDLINE, Pubmed, Ovid and Embase were used to search for clinical studies comparing with or without prophylactic use of lamivudine for HBV reactivation in breast cancer patients receiving chemotherapy. Outcomes of interest were the rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis attributable to HBV reactivation, severity of hepatitis and severity of hepatitis attributable to HBV reactivation, the rate of chemotherapy disruption, and the rate of chemotherapy disruption attributable to HBV reactivation, overall mortality, and mortality attributable to HBV reactivation.ResultsFour studies with 285 patients were included in this meta-analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis related to HBV reactivation were reduced by use of prophylactic lamivudine compared to control group. Pooled Odds Ratios (ORs) were 0.09 (95% confidence intervals [CI] 0.03-0.26; P < 0.0001), 0.23 (95% CI 0.06-0.92; P = 0.04), and 0.10 (95% CI 0.03-0.32; P < 0.0001) respectively. There was a reduction in chemotherapy disruption related to HBV reactivation by use of prophylactic lamivudine (pooled OR = 0.11; 95% CI 0.02-0.58; P = 0.01). Chemotherapy disruption, overall mortality, and mortality attributable to HBV reactivation were not significantly different between two groups. Pooled ORs were 0.42 (95% CI 0.11-1.58; P = 0.20), 0.37 (95% CI 0.07-2.04; P = 0.25), and 0.25 (95% CI 0.01-6.82; P = 0.41) respectively. Lamivudine was well-tolerated, and no additional toxicity was observed.ConclusionsUse of prophylactic lamivudine may have positive effect on the outcome of breast cancer patients with HBsAg positive during chemotherapy.

Reactivation of Hepatitis B During Immunosuppressive Therapy: Potentially Fatal Yet Preventable

Reactivation of Hepatitis B During Immunosuppressive Therapy: Potentially Fatal Yet Preventable

A single-center, prospective and randomized controlled study: Can the prophylactic use of lamivudine prevent hepatitis B virus reactivation in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy?

Over the past four decades, chemotherapy has played an important role in prolonging survival in breast cancer patients. However, it may also result in undesirable side effects such as hepatitis B virus (HBV) reactivation seen in this study. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Several strategies use lamivudine to deal with this problem. Initially, lamivudine had been used to treat patients who developed alanine transaminase elevation attributable to HBV reactivation during chemotherapy. However, using this strategy, fatal reactivation has also been reported. Later studies have suggested that prophylactic lamivudine significantly reduces HBV reactivation and its associated morbidity. However, these studies were based mainly on patients with lymphoma, whereas studies on breast cancer patients were few. Moreover, these studies were retrospective. Recently, a prospective study has recommended that deferred preemptive lamivudine could be a comparable alternative to the prophylactic strategy. However, it was not a randomized controlled study. In this study, it was examined the efficacy of the prophylactic strategy in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy using a prospective, randomized controlled study. Two groups were studied. One group consisted of 21 patients who were treated with prophylactic lamivudine, the other group consisted of 21 patients who were not treated with prophylactic lamivudine. The results showed that the prophylactic lamivudine strategy significantly decreased the incidence of HBV reactivation (0 vs. 28.6%, P = 0.021). It was conclude that the prophylactic lamivudine strategy significantly reduces the incidence of HBV reactivation for hepatitis B s-antigen seropositive breast cancer undergoing chemotherapy.

Prophylactic use of lamivudine for hepatitis B exacerbation in post-operative breast cancer patients receiving anthracycline-based adjuvant chemotherapy

Background:With the increasing incidence of breast cancer worldwide, in particular in southeast Asia (including Korea), and the common use of anthracyclines in the adjuvant and metastatic settings, the occurrence of Hepatitis B virus (HBV) reactivation may develop in this patient population. The use of prophylactic antiviral agents in cancer patients may result in a reduced HBV exacerbation. The purpose of the current study was to assess the efficacy of prophylactic lamivudine in reducing the incidence and severity of HBV reactivation in post-operative breast cancer patients undergoing adjuvant doxorubicin-containing chemotherapy.Methods:The medical records of patients undergoing anthracycline-based adjuvant chemotherapy at Samsung Medical Center between January 2001 and September 2008 were reviewed.Results:From the database, 1912 breast cancer patients who had received anthracycline-based adjuvant chemotherapy were identified. Of 131 patients who were HBV surface antigen positive, 55 and 76 did and did not receive prophylactic lamivudine, respectively. In all, 30 patients (23%) developed hepatitis during doxorubicin-containing adjuvant chemotherapy. Of the 30 patients, 5 (9%) were in the prophylactic lamivudine group and 25 (33%) in the control group (P=0.001). In the prophylactic lamivudine group, there was significantly less HBV reactivation (1 patient (2%) vs 20 patients (16%); P=0.002), less disruption of chemotherapy (7 vs 14% P=0.04), and less severe hepatitis (0 vs 17% P=0.002).Conclusion:Prophylactic lamivudine significantly reduced the incidence and severity of HBV reactivation in breast cancer patients undergoing anthracycline-based adjuvant chemotherapy.

Preventing chemotherapy-induced hepatitis B reactivation in breast cancer patients: a prospective comparison of prophylactic versus deferred preemptive lamivudine

Prophylactic lamivudine to prevent chemotherapy-induced hepatitis B virus (HBV) reactivation has been widely adopted in hematological cancer patients. We examined the deferred preemptive strategy, upon rising viremia, in breast cancer (BC) patients based on sensitive serum HBV DNA level monitoring in a non-randomized controlled study. Baseline virological profiles before cytotoxic chemotherapy were retrospectively analyzed in historical BC and non-BC patients. A prospective cohort study, including 22 early BC patients (Group I) who were hepatitis B surface antigen (HBsAg)± and required adjuvant chemotherapy, were enrolled and had deferred preemptive use of lamivudine upon viremic surge. During the study period, another 23 BC patients, who did not participate in the above-mentioned study, received prophylactic use of lamivudine as routine practice (Group 2). Chemotherapy-induced hepatitis events and the lamivudine treatment course were compared. There was no significant difference in the incidence of hepatitis during chemotherapy between these two groups. Patients in Group I had statistically significant shorter duration of lamivudine use during chemotherapy. However, once lamivudine had been initiated, the treatment course is not significantly shorter than those patients given prophylactically. Deferred preemptive strategy is feasible to control HBV replication and prevent its reactivation in BC patients undergoing chemotherapy. However, it may not be superior to prophylactic strategy and clinically practical.

Biologic Agents in the Treatment of Rheumatic Diseases with Chronic Viral Infection. Where Are We?

Biologic agents have increased the therapeutic armamentarium against immune-mediated disorders, and particularly rheumatic diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Nevertheless, infectious side effects are a major concern in the use of these biologics, especially anti-tumor necrosis factor (TNF) agents1. In this context, the use of TNF blockers in patients with chronic viral infection seems hazardous, and represents an unresolved issue2. In this issue of The Journal , Zingarelli, et al 3 report 3 cases of patients with RA positive for HBsAg, in which anti-TNF therapies (etanercept, infliximab then etanercept, adalimumab) under prophylactic use of lamivudine were not associated with hepatitis reactivation, even after anti-TNF discontinuation with prolonged lamivudine therapy. In one of their cases, an increase in HBV viral load occurred after discontinuation of methotrexate. Methotrexate was reported to induce subfulminant hepatitis B virus reactivation after its withdrawal4,5. This illustrates the interactions of the underlying condition and the associated immunosuppressive therapy that may confuse our interpretation of the responsibility of … Address reprint requests to Dr. Wendling. E-mail: dwendling{at}chu-besancon.fr

Prophylactic use of lamivudine with chronic immunosuppressive therapy for rheumatologic disorders

The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.

Screening for chemotherapy-induced reactivation of hepatitis B virus infection: An institutional experience

20563 Background: In patients with a hepatitis B history (HBV), chemotherapy (CT) can allow the reactivation of HBV, by suppression of the immune system. New-onset HBV may result in varying degrees of hepatocellular injury. Risk factors are detectable hepatitis B surface antigen (HBsAg), pre-CT HBV DNA level, antibodies to hepatitis B core antigen (anti-HBc), treatment with corticosteroids, young age, male gender and lymphoma or breast cancer diagnosis. Lamivudine prophylaxis is recommended to reduce the incidence and severity of hepatitis in this context. Methods: Since October 2006 we tested for HBV infection all pts candidate to CT. The protocol has three sequential levels: HBV markers evaluation; HBV DNA testing in pts HBsAg+ or HBsAg negative but anti-HBc ± anti-HBs positive and with high risk of immune depression; Lamivudine prophylaxis for pts HBsAg+ or HBsAg negative but with detectable HBV DNA. Results: We have screened 301 pts with CT program ongoing:189 (63%) pts were negative for markers of previous HBV infection; on the contrary 112 (37%) had markers positive. Seventeen (15%) of these were HBsAg+, 12 (11%) for anti-HBs alone and 83 (74%) for anti-HBc ± anti-HBs. HBV DNA was tested in all pts HBsAg+ and in 30 of 81 pts with positive markers and high risk of immune depression. HBV DNA was detected in all HBsAg+ pts, while in any of those HBsAg negative but with positive markers. For the last level 15 HBV DNA+ pts were treated by Lamivudine prophylaxis. In 12/15 HBV DNA had negativized within the first three months, in 2/15 the viremia level decreased, and only 1 patient, affected by non-Hodgkin’s lymphoma, experienced HBV reactivation. This patient was resistant to prophylactic therapy. Lamivudine was replaced by Adefovir therapy, but the level of viremia did not change significantly. Conclusions: Our study underlines the need to carefully investigate pts which undergo CT. They should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection, because they must be considered for Lamivudine prophylaxis use. Finally, the prophylactic use of Lamivudine in inactive HBV carriers with hemato-oncological malignancy prevents interruptions in their treatment for primary disease as a result of HBV reactivation. No significant financial relationships to disclose.

Fatal Fulminant Hepatitis B after Withdrawal of Prophylactic Lamivudine in Hematopoietic Stem Cell Transplantation Patients

Hepatitis B virus (HBV) reactivation can give rise to acute hepatitis and even fatal fulminant hepatitis in patients receiving immunosuppressive or cytostatic treatment. Recently, the prophylactic use of lamivudine for HBV reactivation in HBV surface antigen-positive chronic-disease patients undergoing hematopoietic stem cell transplantation (HSCT) has been reported. However, the appropriate duration for this prophylactic therapy is unclear. Here, we report 2 cases of fatal fulminant hepatitis B reactivation in HSCT patients after lamivudine withdrawal. One patient with non-Hodgkin's lymphoma completed 6 courses of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) and autologous peripheral blood SCT (PBSCT). Lamivudine was discontinued 3 months after transplantation. The second patient had acute myeloid leukemia. He received induction chemotherapy and postremission allogeneic PBSCT as late intensified consolidation therapy. Lamivudine treatment was discontinued 10 months after transplantation. In both patients, HBV reactivation 2 to 3 months following lamivudine cessation led to fatal fulminant hepatitis. We suggest that the duration of prophylactic use of lamivudine in chronic HBV carriers receiving HSCT be prolonged until the patient's immune system has been reconstituted.

Lamivudine prophylaxis in HBV carriers with haemato-oncological malignancies who receive chemotherapy

Reactivation of hepatitis B virus (HBV) is a well-recognized complication of chemo/immunosuppressive therapy in individuals who are HBV surface antigen-positive inactive carriers and in individuals with chronic HBV infection. Although it is well established that chemo/immunosuppressive therapy enhances HBV replication with a resultant increase in the viral load and disease activation, the role of prophylactic lamivudine therapy to prevent chemo/immunosuppressive therapy-induced HBV activation in HBV-positive individuals who are to receive chemo/immunosuppressive therapy remains controversial. The aims of the present article are: (i) to determine the effect of lamivudine prophylaxis in HBV carriers with haemato-oncological malignancies who require chemotherapy; (ii) to define the duration and safety of lamivudine in such individuals; and (iii) to identify the effect of lamivudine prophylaxis on the outcome of chemotherapy administered for the primary disease. The data currently available suggest that lamivudine prophylaxis prevents chemotherapy-induced HBV reactivation in HBV carriers with haemato-oncological malignancies who receive chemotherapy. Lamivudine is safe and tolerable in such individuals. The duration of lamivudine prophylaxis is not yet known; however, it would appear prudent to begin lamivudine at the time of the initiation of the chemotherapy and to continue it throughout the period of chemotherapy administration and for at least 1 and possibly 2 years following the discontinuation of the chemotherapy. Finally, the prophylactic use of lamivudine in inactive HBV carriers with haemato-oncological malignancy prevents interruptions in their treatment for primary disease as a result of HBV reactivation.

Evaluation of prophylactic use of lamivudine in HBV-positive patients with malignant lymphoma undergoing chemotherapy

Evaluation of prophylactic use of lamivudine in HBV-positive patients with malignant lymphoma undergoing chemotherapy

The prophylactic use of lamivudine can maintain dose-intensity of doxorubicin in hepatitis-B surface antigen (HBs Ag)-positive patients with non-Hodgkin's lymphoma who received cytotoxic chemotherapy

6607 Background: We investigated the effectiveness of lamivudine to prevent hepatitis flare up due to reactivation of hepatitis-B virus (HBV) in hepatitis-B surface antigen (HBs Ag)-positive patients with Non-Hodgkin's lymphoma (NHL) during cytotoxic chemotherapy. Methods: HBsAg-positive patients with NHL were identified from the lymphoma database of the Asan Medical Center from January 1995 to August 2002, and their medical records were reviewed. We found that 31 patients were received cytotoxic chemotherapy among 41 NHL patients with HBsAg-positive during same period. We divided them into 2 groups of HBs Ag patients with NHL as follows: Group A who received cytotoxic chemotherapy with lamivudine 100mg daily; Group B without any prophylactic antiviral therapy. Results: There were no significant differences between Group A and B in several clinical variables. Seventeen patients (85%) in group B and one patient (9%) in Group A had hepatitis due to reactivation of HBV (p<0.001), with one hepatic failure related death in Group B and none in group A. The mean dose intensity of doxorubicin (Adriamycin) actually delivered was 13.3mg/m2/week (80% Relative Dose intensity [RDI]) in Group A and 9.1mg/m2/week (55% RDI) in Groups B (p<0.001). Conclusions: Our data suggest that the frequency of chemotherapy-related HBV reactivation may be significantly decreased by lamivudine prophylaxis with maintenance of the dosage of adriamycin. No significant financial relationships to disclose.

The prophylactic use of lamivudine can maintain dose-intensity of doxorubicin in hepatitis-B surface antigen (HBs Ag)-positive patients with non-Hodgkin's lymphoma who received cytotoxic chemotherapy

6607 Background: We investigated the effectiveness of lamivudine to prevent hepatitis flare up due to reactivation of hepatitis-B virus (HBV) in hepatitis-B surface antigen (HBs Ag)-positive patien...

The prophylactic use of lamivudine can maintain dose-intensity of adriamycin in hepatitis-B surface antigen (HBs Ag)-positive patients with Non-Hodgkin's lymphoma who receive cytotoxic chemotherapy.

We investigated the effectiveness of lamivudine to prevent hepatitis flare up due to reactivation of hepatitis-B virus (HBV) in hepatitis-B surface antigen (HBsAg)-positive patients with Non-Hodgkin's lymphoma (NHL) during cytotoxic chemotherapy. HBsAg-positive patients with NHL were identified from the lymphoma database of the Asan Medical Center from January 1995 to August 2002, and their medical records were reviewed. We found that 31 patients were received cytotoxic chemotherapy among 41 NHL patients with HBsAg-positive during same period. We divided them into 2 groups of HBsAg patients with NHL as follows: Group A who received cytotoxic chemotherapy with lamivudine 100 mg daily; Group B without any prophylactic antiviral therapy. There were no significant differences between Group A and B in several clinical variables. Seventeen patients (85%) in group B and one patient (9%) in Group A had hepatitis due to reactivation of HBV (p<0.001), with one hepatic failure related death in Group B and none in group A. The mean dose intensity of adriamycin actually delivered was 13.3 mg/m2/week (80% Relative Dose intensity (RDI)) in Group A and 9.1 mg/m2/week (55% RDI) in Groups B (p<0.001). Our data suggest that the frequency of chemotherapy-related HBV reactivation may be significantly decreased by lamivudine prophylaxis with maintenance of the dosage of adriamycin.

Reactivation of precore mutant hepatitis B virus in chemotherapy-treated patients.

A point mutation from G to A at nucleotide (nt) 1896 of the precore region of hepatitis B virus (HBV) DNA has been shown to be associated with fulminant and severe hepatitis. Further studies have suggested that this point mutation, together with additional mutations in the precore promoter, is probably linked to the reactivation of HBV in patients undergoing cytotoxic chemotherapy. Taiwan is an area with a high prevalence of HBV where hepatitis B flare-up has become a serious problem of HBV carriers who must rely on chemotherapy to treat their diseases. The purpose of this study was to examine if nt 1896 mutation was also present in Chinese patients in Taiwan who developed severe liver disease after chemotherapy. MATERIALS AND METHODS. Thirteen HBV carrier patients, including eight patients with lymphoma, two with germ cell tumors, two with breast carcinomas, and one with acute myeloid leukemia, received chemotherapy in the authors' hospital from February 1994 to May 2000. They all received steroid-containing regimens or antiemetics during chemotherapy. These patients were monitored closely for the development of severe hepatitis during or after chemotherapy. Their sera were harvested at different times for direct sequencing of the polymerase chain reaction products of the precore region of HBV DNA. Six of the 13 patients developed severe hepatitis with a fulminant course during or after the completion of chemotherapy. A point mutation from G to A at nt 1896 was detected in five of these six patients. Among those five patients, four had additional precore mutations. The other patient did not have the nt 1896 mutation but had mutations at nt 1835 (A to C). None of the other seven patients lacking the precore nt 1896 mutation developed severe hepatitis flare-up. One of those seven patients who developed moderate elevation of alanine aminotransferase (ALT) without hyperbilirubinemia did have precore mutations other than nt 1896. None of the other six patients had mutations over the precore region. Nucleotide mutation of the precore region, notably at position 1896, is associated with reactivation of HBV with a fulminant course during or after chemotherapy. The current data, together with other investigators' findings, suggest that patients who are HBV carriers with HBV envelope antigen (HBeAg) (-)/anti-HBV envelope antibody (Anti-HBe)(+) status should be assayed to determine if they carry mutant HBV before chemotherapy. Prophylactic use of lamivudine is strongly recommended for patients who carry mutant HBV at precore region, especially at nt 1896 (G to A), before and during chemotherapy.