Copyright ©The Author(s) 2015.
World J Hepatol. May 8, 2015; 7(7): 954-967
Published online May 8, 2015. doi: 10.4254/wjh.v7.i7.954
Table 1 Populations at high risk for hepatitis B virus infection that should be screened[4]
Individuals born in areas of high (≥ 8%) or intermediate prevalence (2%-7%) for HBV (HBsAg positive) including immigrants and adopted children
Asia, Africa, South Pacific Islands: All countries
Middle East (except Cyprus and Israel)
Eastern Europe: All countries except Hungary
European Mediterranean: Malta and Spain
The Arctic (indigenous populations of Alaska, Canada, and Greenland)
South America: Ecuador, Guyana, Suriname, Venezuela, and Amazon regions of Bolivia, Brazil, Colombia, and Peru
Caribbean: Antigua and Barbuda, Dominica, Granada, Haiti, Jamaica, St. Kitts and Nevis, St. Lucia, and Turks and Caicos
Central America: Guatemala and Honduras
Other groups recommended for screening
United States born persons not vaccinated as infants whose parents were born in regions with high HBV endemicity (8%)
Household and sexual contacts of HBsAg-positive persons
Persons who have ever injected drugs
Persons with multiple sexual partners or history of sexually transmitted disease
Men who have sex with men
Inmates of correctional facilities
Individuals with chronically elevated ALT or AST
Individuals infected with HCV or HIV
Patients undergoing renal dialysis
All pregnant women
Persons needing immunosuppressive therapy
Table 2 Immunosuppressive drug classes and corresponding risk estimates of hepatitis B virus reactivation[63,80]
Drug classDrugRisk estimate of HBVrfor HBsAg positiveRisk estimate of HBVr forHBsAg negative/anti-HBc positive
B-cell depleting agentsRituximab (anti-CD20)High (30%-60%)High (> 10%)
Ofatumumab (anti-CD20)
Anthracycline derivativesDoxorubicinHigh (15%-30%)High (> 10%)
TNF-α inhibitorsInfliximabModerate (1%-10%)Moderate (1%)
Cytokine inhibitorsAbatacept (anti-CD80, -86)Moderate (1%-10%)Moderate (1%)
and integrin inhibitorsUstekinumab (anti-IL-12, -23)
Natalizumab (binds α4-integrin)
Vedolizumab [binds integrin α4β7 (LPAM-1)]
Tyrosine kinase inhibitorsImantinibModerate (1%-10%)Moderate (1%)
CorticosteroidsHigh dose, e.g., prednisone ≥ 20 mg for ≥ 4 wkHigh (> 10%)NA
Moderate dose, e.g., prednisone < 20 mg for ≥ 4 wkModerate (1%-10%)Moderate (1%-10%)
Low dose, e.g., prednisone for < 1 wkLow (< 1%)Low (<< 1%)
Intra-articular corticosteroidsLow (< 1%)Low (<< 1%)
Traditional immunosuppressionAzathioprineLow (< 1%)Low (<< 1%)
Table 3 Comparison of International Associations’ guidelines on the management of hepatitis B virus in the setting of chemotherapy and immunosuppression
Association guidelinesHBV screening populationScreening testAntiviral prophylaxisAntiviral drug recommendedMonitoring in untreated
HBsAg + ve, anti-HBc + veHBsAg - ve, Anti-HBc + vefor prophylaxisanti-HBc + ve patients
American Gastroenterological Association 2014[63,80]High risk of HBVr (> 10%)HBsAg and anti-HBc; HBV DNA if serology + veYes (B1)Yes (B1) if taking:Drug with high barrier to resistance is favoured over lamivudine (B2)No recommendation (knowledge gap)
B-cell depleting agentsContinue until at least 6 mo after completion of chemotherapyB-cell depleting agents
Anthracycline derivativesAnthracycline derivatives
High dose corticosteroids (≥ 20 mg prednisone for ≥ 4 wk)Continue until at least 12 mo after completion of chemotherapy for B-cell depleting agents
Moderate risk of HBVr (1%-10%)HBsAg and anti-HBc; HBV DNA if serology + veYes (B2)Yes (B2) if takingDrug with high barrier to resistance is favoured over lamivudine (B2)No recommendation (knowledge gap)
TNF-α inhibitorsContinue until at least 6 mo after completion of chemotherapyTNF-α inhibitors
Cytokine or integrin inhibitorsCytokine or Integrin inhibitors
Tyrosine kinase inhibitorsTyrosine kinase inhibitors
High dose corticosteroids (≥ 20 mg prednisone for ≥ 4 wk)Continue until at least 6 mo after completion of chemotherapy
Low risk of HBVr (< 1%)Routine screening not recommendedNot recommended (B2)Not recommended (B2)Not applicableNo recommendation (knowledge gap)
Traditional immunosuppressionScreen for HBV as per CDC guidelines[4]; manage accordingly
Intra-articular corticosteroids
Systemic corticosteroids for < 1 wk
American Association for the Study of Liver Disease 2009[110]Anyone at high risk of HBV infection; Table 1 (II-3)HBsAg and anti-HBcYes (regardless of HBV DNA level)No recommendation (knowledge gap)Lamivudine (I) or telbivudine (III) if the anticipated treatment duration is short (< 12 mo) and baseline HBV DNA is not detectableMonitoring recommended; no specific test/frequency provided
Maintain for 6 mo completion of chemotherapy (III)Tenofovir or entecavir if anticipated treatment duration > 12 mo (III)
If baseline HBV DNA > 2000 IU/mL, continue antiviral until endpoints as per immunocompetent patients (III)
European Association for the Study of Liver Disease 2012[103]All candidates for chemo- and immunosuppressive therapy (A1)HBsAg and anti-HBc; HBV DNA if serology + veYes (A1)Yes if:Lamivudine if HBV DNA < 2000 IU/mL and the treatment duration is short/finite (B1)ALT and HBV DNA every 1-3 mo
Regardless of HBV DNA levelHBV DNA detectableEntecavir or tenofovir if HBV DNA is high, lengthy or repeated cycles of immunosuppression (C1)Treat upon evidence of HBVr (C1)
Continue until 12 mo after cessation of chemotherapyTaking rituximab (C2)
Bone marrow or stem cell transplantation (C2)
Treat as per HBsAg + ve
No if:
HBV DNA undetectable; monitor
Asian-Pacific Association for the Study of Liver Disease 2012[109]All patients prior to receiving immunosuppression or chemotherapyHBsAg (IVA)YesNo; monitorHBV DNA should be closely monitored and treated with nucleos(t)ide analogue when needed (IVA)
Test anti-HBc if patient due to receive biological agentHBVr prophylaxis with lamivudine; Continue until 6 mo after end of chemotherapy (IA)
Alternatively use entecavir or tenofovir (IIIA)
Continue HBV treatment if clinically indicated (IA)
American Society of Clinical Oncology Provisional Clinical Opinion 2010[111]Advise against routine serological screening. Screen those withHBsAg; anti-HBc if receiving rituximabConsider role of antiviral therapyNo specific recommendation providedNo specific recommendation providedNo specific recommendation provided
High risk of HBV exposure; evidence of liver diseaseDo not delay chemotherapy
Therapeutic regimen with high risk of HBVr including all patients undergoing rituximab therapy
Haematopoetic stem cell transplant