Systematic review with network meta-analysis: Comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation

Abstract

ObjectivesCurrently, no consensus exists regarding the optimal oral prophylactic regimens for hepatitis B surface antigen seropositive patients undergoing chemotherapy. We aimed to compare the efficacy of oral nucleos(t)ide analogues (NAs), including lamivudine, entecavir, adefovir, telbivudine and tenofovir, for the prevention of chemotherapy-induced hepatitis B virus (HBV) reactivation and its related morbidity and mortality in patients with chronic HBV (CHB) infection.ResultsFifty-two eligible articles consisting of 3892 participants were included. For HBV reactivation, prophylactic treatment with NAs were all significantly superior to no prophylaxis, with odds ratio (OR) from 0.00 (95% confidence interval [CI] 0.00~0.04) for the most effective intervention (tenofovir) to 0.10 (95% CI 0.06~0.14) for the least effective intervention (lamivudine). For secondary outcomes, prophylaxis with NAs also significantly outperformed observation. The results suggested that entecavir reduced the risk of HBV related hepatitis (predicted probability, 83%), HBV related death (68%) and all causes of hepatitis (97%) most efficaciously. It ranked second in decreasing all causes of death (34%).Materials and MethodsPubMed, Embase and Cochrane Library database were searched for controlled trials up to March 31, 2015. Primary outcome was the incidence of HBV reactivation. Secondary outcomes included the incidence of HBV-related hepatitis and death, all causes of hepatitis and death. Network meta-analysis combined direct and indirect evidence to estimate ORs for the clinical outcomes. A mean ranking and the probability of optimal therapeutic regime was obtained for each treatment based on clinical outcomes.ConclusionsAvailable evidence suggests that prophylatic therapy with tenofovir and entecavir may be the most potent interventions in prevention of HBV reactivation and HBV-related morbidity and mortality for CHB infection patients undergoing chemotherapy.

Hepatitis B Reactivation Associated With Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions

“…Interferon-based therapies are not used for prophylaxis. A recent network meta-analysis has shown that tenofovir and entecavir may be the most efficacious therapies for the prevention of HBV reactivation 82 . Decision analyses have shown that it is cost-effective to screen for HBsAg and anti-HBc in patients undergoing lymphoma chemotherapy or early stage breast cancer 83, 84 .…”

“…Prophylaxis should ideally be started 2 to 4 weeks before the initiation of immunosuppressive therapy and maintained for at least 6 months after the last dose of immunosuppressive therapy. It is recommended to use either entecavir or tenofovir as first line antiviral agents 82 . Among those who are inactive HBsAg carriers who may be exposed to low-risk immune suppressive therapy and patients with HBsAg negative/anti-HBc positive (HBV infection in the past), the strategy should be monitoring of viral reactivation with aminotransferases and HBV DNA determination in every 3 months.…”

Reactivation of Hepatitis B Virus and Its Prevention in Patients with Rheumatic Diseases Receiving Immunosuppressive Therapy

“…Incidence and clinical outcomes of HBV reactivation in cancer patients receiving chemotherapy Table 1 summarized the incidence of HBV reactivation in HBV carriers with immunosuppressive therapy [5][6][7]. The incidences of HBV-related hepatitis, liver failure and death in cancer patients receiving chemotherapy have been reported to be 2%∼60%, 6.7%∼33% and 0.4%∼20%, respectively [5,7].…”

“…There is no RCT of prophylactic antiviral treatment with tenofovir. Zhang et al [6] reported that entecavir and tenofovir are the most effective in prophylaxis of HBV reactivation in meta-analysis. Thus, entecavir or tenofovir are preferentially recommended for prophylactic treatment of HBV reactivation [80,81].…”

“…Recent meta-analyses have shown that prophylactic antiviral therapy can prevent the development of HBV reactivation, HBV-related hepatitis, hepatic failure and death in patients receiving immunosuppressive therapy [5][6][7]. However, up to 50% of clinicians did not screen for HBV before immunosuppressive therapy [8,9].…”