Lamivudine Prophylaxis Is Effective in Reducing HBV Mortality in Chemo
Lamivudine Prophylaxis Is Effective in Reducing HBV Mortality in Chemo
Background: Hepatitis B viral (HBV) reactivation in patients undergoing chemotherapy is associated with significant morbidity and mortality. Lamivudine has been suggested to be useful as a prophylaxis for HBV reactivation; however, its impact on overall survival and HBV reactivation-related liver disease survival is unclear.
Objective: To determine the effect of lamivudine prophylaxis on the rate of HBV reactivation, overall survival and HBV reactivation-related survival in patients with HBV undergoing chemotherapy.
Methods: A comprehensive search of MEDLINE, Cochrane Collaboration Database, reference lists and abstracts from national meetings. Statistical analysis was performed using revman.
Results: Eleven studies met the defined inclusion criteria and were included in the analysis. Two-hundred and twenty patients received lamivudine prophylaxis and 400 did not receive prophylaxis. Patients given lamivudine prophylaxis had an 87% decrease in HBV reactivation [risk ratio (RR) 0.13, 95% confidence interval (CI), 0.07-0.24] than patients not given prophylaxis [absolute risk reduction (ARR) -0.46, 95% CI, -0.61 to -0.31]. The number needed to treat to prevent one reactivation was 3. The Lamivudine prophylaxis group was also associated with a 70% reduction in reactivation-related mortality (RR 0.30, 95% CI, 0.1-0.94) compared with controls (ARR -0.03, 95% CI, 0.07-0.00). There was a reduction in treatment delays and premature termination of chemotherapy in the lamivudine prophylaxis arm (RR 0.41, 95% CI, 0.27-0.63; ARR -0.33, 95% CI, -0.33 to -0.15). There was no significant heterogeneity in the comparisons.
Conclusion: Lamivudine prophylaxis during chemotherapy is effective in reducing the rate of HBV reactivation, and reactivation-related liver mortality. Patients with lamivudine prophylaxis had less chemotherapy treatment delays and premature termination of their chemotherapy. Few patients need to be treated to prevent reactivation. Patients with HBV undergoing chemotherapy should be started on lamivudine prophylaxis.
Chronic hepatitis B is a major public and medical concern around the world. There are an estimated 350 million infected individuals worldwide, and approximately 1.25 million infected in the United States. Patients with chronic hepatitis B are at increased risk of liver failure, cirrhosis and hepatocellular carcinoma. Liver failure may occur in the context of hepatitis B reactivation associated with immunosuppressive or cytotoxic therapy. The mortality rate with hepatitis B flare in patients receiving cytotoxic chemotherapy is between 10 and 50%. Unfortunately, the very diseases that lead to use of chemotherapy often preclude eligibility for liver transplantation.
Patients with chronic hepatitis B who undergo chemotherapy are not only at risk of hepatitis flare with chemotherapeutic regiment interruption but also of increased mortality from the flare. Interruption of chemotherapy dose or frequency may impact its response. Similarly, maintenance of immunosuppression may prevent graft-vs.-host disease in patients undergoing allogeneic stem cell transplantation. The impact of the interruption in therapy because of hepatitis B reactivation on survivability, disease progression and graft function is not clearly understood by current studies.
Lamivudine is an oral nucleoside reverse transcriptase inhibitor with activity against hepatitis B. It is effective in rapidly decreasing viral load, and is associated with few adverse effects. Widespread use is limited by the emergence of resistant viral strains. Several studies have demonstrated that lamivudine prophylaxis results in a decreased risk of hepatitis B reactivation. However, the impact on preventing a flare/reactivation on overall survival and disease-specific survival is not known. Furthermore, disease- and patient-specific factors that can impact the severity of reactivation and the efficacy of prophylaxis are unknown.
The purpose of this meta-analysis was to study the impact of lamivudine prophylaxis on patients with chronic hepatitis B undergoing chemotherapy. Our hypothesis was that lamivudine prophylaxis reduces the rate of HBV reactivation, overall and liver-associated mortality, chemotherapy delay and termination.
Abstract and Introduction
Abstract
Background: Hepatitis B viral (HBV) reactivation in patients undergoing chemotherapy is associated with significant morbidity and mortality. Lamivudine has been suggested to be useful as a prophylaxis for HBV reactivation; however, its impact on overall survival and HBV reactivation-related liver disease survival is unclear.
Objective: To determine the effect of lamivudine prophylaxis on the rate of HBV reactivation, overall survival and HBV reactivation-related survival in patients with HBV undergoing chemotherapy.
Methods: A comprehensive search of MEDLINE, Cochrane Collaboration Database, reference lists and abstracts from national meetings. Statistical analysis was performed using revman.
Results: Eleven studies met the defined inclusion criteria and were included in the analysis. Two-hundred and twenty patients received lamivudine prophylaxis and 400 did not receive prophylaxis. Patients given lamivudine prophylaxis had an 87% decrease in HBV reactivation [risk ratio (RR) 0.13, 95% confidence interval (CI), 0.07-0.24] than patients not given prophylaxis [absolute risk reduction (ARR) -0.46, 95% CI, -0.61 to -0.31]. The number needed to treat to prevent one reactivation was 3. The Lamivudine prophylaxis group was also associated with a 70% reduction in reactivation-related mortality (RR 0.30, 95% CI, 0.1-0.94) compared with controls (ARR -0.03, 95% CI, 0.07-0.00). There was a reduction in treatment delays and premature termination of chemotherapy in the lamivudine prophylaxis arm (RR 0.41, 95% CI, 0.27-0.63; ARR -0.33, 95% CI, -0.33 to -0.15). There was no significant heterogeneity in the comparisons.
Conclusion: Lamivudine prophylaxis during chemotherapy is effective in reducing the rate of HBV reactivation, and reactivation-related liver mortality. Patients with lamivudine prophylaxis had less chemotherapy treatment delays and premature termination of their chemotherapy. Few patients need to be treated to prevent reactivation. Patients with HBV undergoing chemotherapy should be started on lamivudine prophylaxis.
Introduction
Chronic hepatitis B is a major public and medical concern around the world. There are an estimated 350 million infected individuals worldwide, and approximately 1.25 million infected in the United States. Patients with chronic hepatitis B are at increased risk of liver failure, cirrhosis and hepatocellular carcinoma. Liver failure may occur in the context of hepatitis B reactivation associated with immunosuppressive or cytotoxic therapy. The mortality rate with hepatitis B flare in patients receiving cytotoxic chemotherapy is between 10 and 50%. Unfortunately, the very diseases that lead to use of chemotherapy often preclude eligibility for liver transplantation.
Patients with chronic hepatitis B who undergo chemotherapy are not only at risk of hepatitis flare with chemotherapeutic regiment interruption but also of increased mortality from the flare. Interruption of chemotherapy dose or frequency may impact its response. Similarly, maintenance of immunosuppression may prevent graft-vs.-host disease in patients undergoing allogeneic stem cell transplantation. The impact of the interruption in therapy because of hepatitis B reactivation on survivability, disease progression and graft function is not clearly understood by current studies.
Lamivudine is an oral nucleoside reverse transcriptase inhibitor with activity against hepatitis B. It is effective in rapidly decreasing viral load, and is associated with few adverse effects. Widespread use is limited by the emergence of resistant viral strains. Several studies have demonstrated that lamivudine prophylaxis results in a decreased risk of hepatitis B reactivation. However, the impact on preventing a flare/reactivation on overall survival and disease-specific survival is not known. Furthermore, disease- and patient-specific factors that can impact the severity of reactivation and the efficacy of prophylaxis are unknown.
The purpose of this meta-analysis was to study the impact of lamivudine prophylaxis on patients with chronic hepatitis B undergoing chemotherapy. Our hypothesis was that lamivudine prophylaxis reduces the rate of HBV reactivation, overall and liver-associated mortality, chemotherapy delay and termination.
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