Prevention of hepatitis B reactivation in patients requiring chemotherapy and immunosuppressive therapy

Table 1 Immunosuppressive agent classes and corresponding risks of hepatitis B reactivation

Risk group	Seropositive for HBsAg and anti-HBc	Seronegative for HBsAg, seropositive for anti-HBc
High risk (> 10%)	Anti-CD20 antibodies	Anti-CD20 antibodies
	Anti-CD52 antibodies
	Anthracycline derivatives
	Costimulation inhibitors
	JAK inhibitors
	Moderate-high dose corticosteroid therapy1 for ≥ 4 wk
Moderate risk (1%-10%)	TNF-α inhibitors	Anthracycline derivatives
	Integrin inhibitors	TNF-α inhibitors
	IL-12 and IL-23 antibodies	Integrin inhibitors
	Tyrosine kinase inhibitors	IL-12 and IL-23 antibodies
	Low dose corticosteroid therapy1 for ≥ 4 wk	Tyrosine kinase inhibitors
		Moderate-high dose corticosteroid therapy1 for ≥ 4 wk
Low risk (< 1%)	General immunosuppressive agents (azathioprine, 6-mercaptopurine and methotrexate)	General immunosuppressive agents (azathioprine, 6-mercaptopurine and methotrexate)
	Corticosteroid therapy1 for ≤ 1 wk	Low dose corticosteroid therapy1 for ≥ 4 wk
	Intra-articular corticosteroids	Corticosteroid therapy1 for ≤ 1 wk
		Intra-articular corticosteroids

¹Corticosteroid therapy: Prednisone (or equivalent); low dose (< 10 mg), moderate dose (10-20 mg), high dose (> 20 mg). anti-HBc: Hepatitis B core antibodies; HBsAg: Hepatitis B surface antigen; IL: Interleukin; JAK: Janus kinase; TNF: Tumor necrosis factor.

Table 2 Recommendations of international guidelines for treatment and follow-up in different clinical scenarios

	AASLD 2018	EASL 2017	APASL 2016	AGA 2015
Screening before chemotherapy/immunosuppressive therapy	HBsAg and anti-HBc	HBsAg, anti-HBc, and anti-HBs	HBsAg and anti-HBc	HBsAg and anti-HBc
				HBV DNA if serology positive
Start antiviral prophylaxis before chemotherapy/immunosuppressive therapy	For HBsAg (+) patients	For HBsAg (+) patients	For HBsAg (+) patients	For HBsAg (+) patients
		For HBsAg (-)/anti-HBc (+) patients: if at high risk of HBV reactivation	For HBsAg (-)/anti-HBc (+) patients: if detectable serum HBV DNA	For HBsAg (-)/anti-HBc (+) patients: If the chemotherapy is associated with high or moderate risk of HBV reactivation
Treatment duration of antiviral treatment after completing chemotherapy/immunosuppressive therapy	At least 6 mo	12 mo	12 mo	At least 6 mo
	At least 12 mo for patients receiving anti-CD20 antibodies therapy			At least 12 mo for patient receiving anti-CD20 antibodies therapy
Antivirals of choice	TDF, TAF or ETV	TDF, TAF or ETV	TDF and ETV	TDF and ETV

AASLD: American Association for the Study of Liver Diseases; AGA: American gastroenterology association; anti-HBc: Hepatitis B core antibodies; APASL: Asian pacific association for the study of the liver; EASL: European association for the study of the liver; ETV: Entecavir; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; TAF: Tenofovir alafenamide; TDF: Tenofovir disoproxil fumarate.