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

Table 2 Studies of hepatitis B virus reactivation in patients receiving Bruton’s tyrosine kinase inhibitors (all studies are retrospective)

Ref.	Disease type		Therapy	N			CHB, n		Past resolved HBV infection, n	Antiviral prophyl-axis, % patients		Definition of HBV reactivation		Rate of HBV reactivation, % patients	HBV-related death
Hammond et al[108], 2018	CLL, MCL, LPL		Ibrutinib	21			0		21	4.8%		HBV DNA > 100 IU/mL on 2 consecutive measurements ± reappearance of HBsAg		9.5%	0
Innocenti et al[109], 2019	CLL		Ibrutinib	34			0		12	42% for past infection (lamivudine)		Increase in serum ALT and HBV DNA in HBsAg-positive patients or elevation of HBV DNA ± HBsAg recurrence in anti-HBc-positive patients		8.3%	0
Innocenti et al[110], 2022	CLL		Ibrutinib	108			0		108	67.6% (lamivudine)		HBsAg seroconversion and/or an increase of serum HBV DNA by ≥ 1 log above the LLD of the assay		1.9%	0
Ni et al[111], 2022	DLBCL		Ibrutinib or zanu-brutinib	55			4		26	100% for CHB and 34.6% for past infection (entecavir)		> 1 log increase in HBV DNA, HBV DNA-positive when previously negative, HBV DNA > 2000 IU/mL if no baseline level was available, or reverse seroconversion from HBsAg-negative to -positive		7.69% for past infection	0

CHB: Chronic hepatitis B; CLL: Chronic lymphocytic leukaemia; DLBCL: Diffuse large B-cell lymphoma; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; LLD: Lower limit of detection; LPL: Lymphoplasmacytic lymphoma; MCL: Mantle cell lymphoma; ALT: Alanine aminotransferase; anti-HBc: Antibody to hepatitis B core.