Hepatitis B reactivation in patients with hepatitis B core antibody positive and surface antigen negative on immunosuppressants

Table 1 Definition of key terms used in the study of hepatitis B virus reactivation

Key term	Definition
Resolved Hepatitis B infection	Negative HBsAg, positive anti-HBc, positive anti-HBs
Past Hepatitis B infection	Negative HBsAg, positive anti-HBc, negative or unknown anti-HBs
HBV reactivation	In HBsAg-negative, anti-HBc-positive patients: Newly detectable HBV DNA level OR; Occurrence of HBsAg sero-reversion (reappearance of HBsAg)
Hepatitis B flare	ALT increase to ≥ 3 times the baseline level and > 100 U/L
HBV-associated liver failure	Impaired synthetic function (Total bilirubin > 3 mg/dL or international normalized ratio > 1.5) OR Ascites OR Encephalopathy OR Death following HBV-associated liver failure attributed to HBV reactivation
Antiviral prophylaxis	Antiviral treatment in a patient where there are no other indications for commencing treatment other than an anticipated HBV reactivation
On-demand treatment	Commencement of antiviral treatment upon diagnosis of HBV reactivation

HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; Anti-HBc: Antibody to Hepatitis B core antigen; Anti-HBs: Antibody to Hepatitis B surface antigen.

Table 2 Risk factors determining risk of hepatitis B reactivation in HBsAg negative, anti-HBc positive patients. Hepatitis B chemoprophylaxis can be considered in patients with 2 or more high risk factors for hepatitis B reactivation

Category	Risk factor
Virological factors	(1) High baseline HBV DNA; (2) Absence of anti-HBs antibody; (3) Presence of Hepatitis B core-related antigen
Patient factors	(1) Male gender; (2) Liver cirrhosis; (3) Immunosuppression required because of hematological malignancy
Type of immunosuppressive regime	High risk: B-cell depleting therapies
	Medium risk: Anthracycline derivatives, high dose corticosteroids, systemic cancer chemotherapy, cytokine-based therapies, immunophilin inhibitors, tyrosine-kinase inhibitors, protease inhibitors
	Low risk: Immune checkpoint inhibitors, low-moderate dose corticosteroids, antimetabolite therapies