Copyright ©The Author(s) 2016.
World J Gastroenterol. Jul 28, 2016; 22(28): 6484-6500
Published online Jul 28, 2016. doi: 10.3748/wjg.v22.i28.6484
Table 1 Drug classes and corresponding risks of HBV reactivation[49,67]
Drug classDrugRisk of HBV reactivation for HBsAg-positive patientsRisk of HBV reactivation for HBsAg-negative/anti-HBc-positive patients
Monoclonal antibodyRituximabHigh (30%-60%)High (> 10%)
Anthracycline chemotherapyDoxorubicinHigh (15%-30%)High (> 10%)
CorticosteroidsHigh dose, e.g., Prednisolone ≥ 20 mg for ≥ 4 wkHigh (> 10%)Not available
Moderate dose, e.g., Prednisolone < 20 mg for ≥ 4 wkModerate (1%-10%)Moderate (1%-10%)
Low dose, e.g., Prednisolone < 1 wkLow (< 1%)Low (< 1%)
Tyrosine kinase inhibitorsImatinib, nilotinibModerate (1%-10%)Moderate (1%-10%)
Traditional immunosuppressive agentsMethotrexate, azathioprine, 6-mercaptopurineLow (< 1%)Low (< 1%)
Table 2 Prospective studies on HBV reactivation in haematology patients with resolved hepatitis B virus infection (HBsAg negative anti-HBc positive patients)
Author/yearDiseaseStudy designSample sizeDefinition of HBV reactivationRate of HBV reactivationRisk factor(s) identified for HBV reactivationDeath from HBV reactivation
Yeo et al[99] 2009Diffuse large B-cell lymphomaAll patients were observed every 2-3 wk during anticancer therapy and every 6-8 wk for 9 mo after anticancer therapy46HBsAg seroconversion (the reappearance of HBsAg) with an increase in HBV DNA levels when compared with baseline HBV DNA levels, in the absence of acute infection with HAV, HCV, or other systemic infections25% in patients receiving R-CHOPAbsence of anti-HBs, use of rituximab and male sex20% died of HBV reactivation
Start lamivudine upon HBV reactivation
Huang et al[107] 2013B-cell lymphomaEntecavir prophylaxis (continued until 3 mo after completing chemotherapy) vs preemptive treatment80Elevation of HBV viral load to 2000 IU/mL with two consecutive determinations (2 wk apart)Incidence was 4.3% in entecavir group and 25.9% in the control group at 1.5 yrLack of entecavir prophylaxisNil
Seto et al[45] 2014CD20 positive B-cell lymphomaHBV DNA monitoring every 4 wk63HBV DNA ≥ 10 IU/mL2-yr cumulative rate 41.5%Anti-HBs < 10 mIU/mLNil
Start entecavir upon detection of HBV reactivation
Hsu et al[16] 2014CD20 positive B-cell lymphomaHBV DNA monitoring every 4 wk150> 10-fold increase in HBV DNA, compared with previous nadir levelsIncidence was 10.4%Absence of anti-HBsNil
Start entecavir upon detection of HBV reactivation
Kusumoto et al[46] 2015CD20 positive B-cell lymphomaHBV DNA monitoring every 4 wk269HBV DNA ≥ 11 IU/mLIncidence was 8.3% at 1.5 yrAnti-HBs < 10 mIU/mL and baseline HBV DNA below level of quantificationNil
Start entecavir upon detection of HBV reactivation
Table 3 Comparison of international guidelines on the management of patients with hepatitis B virus infection receiving chemotherapy
Association guidelinesHBV screeningScreening testsHBsAg positive patientsHBsAg negative, anti-HBc positive patientsAntiviral drug recommendedDuration of antiviral therapy
EASL 2012[91]All candidates for chemo- and immunosuppressive therapyHBsAg, anti-HBc, HBV DNA if serology positiveProphylactic antiviral therapy, test for HBV-DNA levelTest for HBV DNA; provide prophylactic antiviral therapy if detectable HBV DNA; monitor ALT and HBV DNA levels closely if no detectable HBV DNALamivudine if HBV DNA < 2000 IU/mL and the treatment duration is finite and short, Entecavir or tenofovir if HBV DNA is high, and/or lengthy and repeated cycles of immunosuppression12 mo after cessation of therapy
APASLD 2012[92]All patients prior to receiving immunosuppression or chemotherapyHBsAg, anti-HBcProphylactic antiviral therapyMonitor HBV-DNALamivudine or entecavir or tenofovirContinue until 6 mo after end of chemotherapy
AGA 2015[49]High risk of HBV reactivation (> 10%) and moderate risk of HBV reactivation (1%-10%)HBsAg, anti-HBc , HBV DNA if serology positiveProphylactic antiviral therapyAntiviral prophylaxis over monitoring for patients if the chemotherapy is associated with high or moderate risk of HBV reactivationDrug with high barrier to resistance is favored over lamivudine6 mo after discontinuation of therapy and at least 12 mo for B-cell depleting agents
Routine screening not recommended for low risk of HBV reactivation (< 1%)
AASLD 2009[93], no update in the version in 2016[126]Anyone at high risk of HBV infectionHBsAg and anti-HBcProphylactic antiviral therapyNo recommendationLamivudine or telbivudine if the anticipated treatment duration is < 12 mo and baseline HBV DNA is not detectableMaintain for 6 mo after completion of chemotherapy
Tenofovir or entecavir if anticipated treatment duration > 12 mo
ASCO 2015[94]Risk-adapted HBV screening strategyHBsAg, anti-HBc , HBV DNA if serology positiveProphylactic antiviral therapyConsiderEntecavir, tenofovirMinimum of 6 mo after stopping therapy, longer than 12 mo for patients receiving anti-CD20 monoclonal antibodies
Antiviral prophylaxis if the systemic cancer therapy is associated with high risk of HBV reactivation