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


RESULTS
Fifty-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%).


METHODS
PubMed, 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.


CONCLUSIONS
Available 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.
Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Min-Yue
MY
Zhang
Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China.
Gui-Qi
GQ
Zhu
Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China.
Ke-Qing
KQ
Shi
Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China.
Ji-Na
JN
Zheng
Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China.
Zhang
Z
Cheng
Department of Infection Diseases, the First Hospital of Jiaxing, Jiaxing 314000, China.
Zhuo-Lin
ZL
Zou
Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Hong-Hui
HH
Huang
Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Fang-Yuan
FY
Chen
Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China.
Ming-Hua
MH
Zheng
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects; D000998:Antiviral Agents / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006509:Hepatitis B / Q000139:chemically induced / Q000517:prevention & control* / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014775:Virus Activation / Q000187:drug effects*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D063065:Organophosphonates; D000077712:Telbivudine; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine; D013936:Thymidine
chemotherapy; hepatitis B virus reactivation; indirect comparison; network meta-analysis; nucleos(t)ide analogues prophylaxis