Challenges in the discontinuation of chronic hepatitis B antiviral agents

Table 6 Summary of follow-up interval and retreatment criteria

Ref.	Follow-up interval	Criteria of retreatment
Berg et al[42], 2017	Every 2 wk in the first 3 mo, every 4 wk until week 48, and every 12 wk thereafter until week 144	Two consecutive total bilirubin > 1.5 mg/dL plus ALT > ULN
		Two consecutive PT ≥ 2.0 seconds (INR ≥ 0.5) prolonged from baseline with adequate vitamin K therapy plus ALT > ULN
		Two consecutive ALT > 10 × ULN
		ALT > 2 × but ≤ 5 × ULN persisting for ≥ 12 wk plus HBV DNA > 20000 copies/mL
		ALT 5 × but ≤ 10 × ULN persisting for ≥ 4 wk
Papatheodoridi et al[63], 2018	Every mo in the first 3 mo then at least every 3 mo until month 12	Greece cohort: (1) ALT > 10 × ULN; (2) ALT > 5 × ULN plus total bilirubin > 2 mg/dL; (3) ALT > 3 × ULN plus HBV DNA > 100000 IU/mL; and (4) ALT > ULN plus HBV DNA > 2000 IU/mL on three sequential occasions
		Taiwanese cohort: (1) ALT > 2 × ULN twice 3 mo apart plus HBV DNA > 2000 IU/mL; (2) Total bilirubin > 2 mg/dL; and (3) PT ≥ 3 seconds of control range
Liem et al[39], 2019	Wk 4, 6, 12, 18, 24, 36, 48, 60, and 72	HBeAg seroreversion
		HBV DNA > 2000 IU/mL plus ALT > 600 IU/mL
		HBV DNA > 2000 IU/mL plus ALT > 5 × ULN (40 IU/mL) on two consecutive visits
		HBV DNA > 2000 IU/mL plus ALT > 200 IU/mL but < 600 IU/mL for > 6–8 wk
		HBV DNA > 20000 IU/mL on two consecutive visits at least 4 wk apart
García-López et al[60], 2020	Monthly in the first 6 mo then every 3-4 mo until 24 mo	Two consecutive ALT > 10 × ULN regardless of HBV DNA level
		ALT > 5-10 × ULN and HBV DNA > 2000 IU/mL persisting for ≥ 4 wk
		ALT > 2-5 × ULN and HBV DNA > 2000 IU/mL persisting for ≥ 6 mo
		Need for immunosuppressive treatment

ALT: Alanine aminotransferase; HBeAg: Hepatitis B e antigen; HBV: hepatitis B virus; INR: International normalized ratio; PT: Prothrombin time; ULN: Upper limit of normal.