Hepatitis B reactivation in the setting of chemotherapy and immunosuppression - prevention is better than cure

Table 3 Comparison of International Associations’ guidelines on the management of hepatitis B virus in the setting of chemotherapy and immunosuppression

Association guidelines	HBV screening population	Screening test	Antiviral prophylaxis		Antiviral drug recommended	Monitoring in untreated
			HBsAg + ve, anti-HBc + ve	HBsAg - ve, Anti-HBc + ve	for prophylaxis	anti-HBc + ve patients
American Gastroenterological Association 2014[63,80]	High risk of HBVr (> 10%)	HBsAg and anti-HBc; HBV DNA if serology + ve	Yes (B1)	Yes (B1) if taking:	Drug with high barrier to resistance is favoured over lamivudine (B2)	No recommendation (knowledge gap)
	B-cell depleting agents		Continue until at least 6 mo after completion of chemotherapy	B-cell depleting agents
	Anthracycline derivatives			Anthracycline 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 + ve	Yes (B2)	Yes (B2) if taking	Drug with high barrier to resistance is favoured over lamivudine (B2)	No recommendation (knowledge gap)
	TNF-α inhibitors		Continue until at least 6 mo after completion of chemotherapy	TNF-α inhibitors
	Cytokine or integrin inhibitors			Cytokine or Integrin inhibitors
	Tyrosine kinase inhibitors			Tyrosine 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 recommended	Not recommended (B2)	Not recommended (B2)	Not applicable	No recommendation (knowledge gap)
	Traditional immunosuppression	Screen 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-HBc	Yes (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 detectable	Monitoring 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 + ve	Yes (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 level	HBV DNA detectable	Entecavir 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 chemotherapy	Taking 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 chemotherapy	HBsAg (IVA)	Yes	No; monitor		HBV DNA should be closely monitored and treated with nucleos(t)ide analogue when needed (IVA)
		Test anti-HBc if patient due to receive biological agent	HBVr 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 with	HBsAg; anti-HBc if receiving rituximab	Consider role of antiviral therapy	No specific recommendation provided	No specific recommendation provided	No specific recommendation provided
	High risk of HBV exposure; evidence of liver disease		Do not delay chemotherapy
	Therapeutic regimen with high risk of HBVr including all patients undergoing rituximab therapy
	Haematopoetic stem cell transplant

The grade of recommendation and/or level of evidence have been noted where available. AGA and EASL guidelines: evidence grade A: High quality; B: Moderate quality; C: Low quality. Recommendation grade 1: Strong; 2: Weak. I: Randomised controlled trials; AASLD guidelines: II-1: Non-randomised controlled trials; II-2: Cohort or case-control studies; II-3: Case series; III: Expert opinion. APASL guidelines: Quality of evidence ranked from I (highest) to V (lowest); strength of recommendations ranked A (strongest) to D (weakest). HBV: Hepatitis B virus; HBVr: Hepatitis B virus reactivation; CDC: The Centre for Disease Control; + ve: Positive; - ve: Negative; ALT: Alanine aminotransferase.