Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

Table 5 International guidelines on prevention of hepatitis B in patients with a history of hepatitis B virus infection who are candidates for chemotherapy

Guideline	HBV screening	Screening tests	HBsAg-positive patients	HBsAg-negative, anti-HBc-positive patients	Choice of antiviral agent	Duration of antiviral therapy	Monitoring after prophylaxis	Ref.
American Gastroenterological Association 2015 guideline	High risk of HBV reactivation (> 10%) and moderate risk of HBV reactivation (1%-10%). Routine screening not recommended for low risk of HBV reactivation (< 1%)	HBsAg, anti-HBc, HBV DNA if serology positive	Prophylactic antiviral therapy	Antiviral prophylaxis over monitoring for patients if the chemotherapy is associated with high or moderate risk of HBV reactivation	Drug with high barrier to resistance is favored over LMV	6 mo after discontinuation of therapy and at least 12 mo for B-cell depleting agents	Not defined	[6]
European Association for the Study of the Liver 2017	All candidates for CT or IST	HBsAg, anti-HBc, and anti-HBs	Anti-HBV prophylaxis	Anti-HBV prophylaxis if they are at high risk of HBV reactivation. Pre-emptive therapy for moderate (10%) or low (1%) risk of HBV reactivation, and monitor HBsAg and/or HBV DNA every 1-3 mo during and after IST	ETV or TDF or TAF	At least 12 mo (18 mo for high-risk therapy) after the last course of therapy	LFT and HBV DNA every 3 to 6 mo during prophylaxis and for ≥ 12 mo after NA withdrawal	[3]
American Association for the Study of Liver Diseases 2018	All patients for CT and IST	HBsAg and anti-HBc	Anti-HBV prophylaxis	On-demand therapy except for patients receiving anti-CD20 antibody therapy or SCT (monitor ALT, HBV DNA, HBsAg every 1-3 mo)	ETV or TDF or TAF	At least 6 mo after discontinuation of IST. At least 12 mo for B cell-depleting agents	For up to 12 mo after cessation of anti-HBV therapy	[7]
American Society of Clinical Oncology 2020 update	All candidates for CT or IST	HBsAg, anti-HBc, and anti-HBs	Anti-HBV prophylaxis	High risk, e.g., anti-CD20 antibody therapy or stem cell transplantation: Prophylaxis. Others: On-demend therapy (monitor HBsAg and HBV DNA every 3 mo)	ETV, TDF, TAF	At least 12 mo after cessation of IST	High risk: Monthly for the first 3 mo after NA withdrawal and then every 3 mo (duration not specified). Resolved HBV and not high risk: Not necessary	[4]
The Asian Pacific Association for the Study of the Liver 2021	All patients planned to receive IST	HBsAg, anti-HBs and anti-HBc, quanti-tative HBV DNA for HBsAg-positive patients	Anti-HBV prophylaxis in high and moderate-risk groups, and low-risk group with advanced liver fibrosis or cirrhosis. Pre-emptive treatment in low-risk group without advanced liver fibrosis or cirrhosis	Anti-HBV prophylaxis in high-risk group and moderate-risk group with advanced liver fibrosis or cirrhosis. Pre-emptive treatment in low-risk group without advanced liver fibrosis or cirrhosis	ETV, TDF or TAF	6 mo after the completion of IST for HBsAg-positive patients, without advanced liver fibrosis or cirrhosis and with low level of HBV DNA	HBV DNA every 3 mo	[5]

High risk of hepatitis B virus reactivation (> 10%), moderate risk (1%-10%), low risk (< 1%). ALT: Alanine aminotransferase; CT: Chemotherapy; ETV: Entecavir; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; IST: Immunosuppresive therapy; LFT: Liver function test; LMV: Lamivudine; NA: Nucleotide analog; SCT: Stem cell transplant; TDF: Tenofovir; TAF: Tenofovir alafenamide fumarate; anti-HBc: Antibody to hepatitis B core; TAF: Tenofovir alafenamide; TDF: Tenofovir disoproxil fumarate.