Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B

Table 3 Updates on combination therapy

Ref.	Treatment		% loss of HBV markers				% seroconvert		% normal ALT	% HBV reactivation
	Type	Schedule	HBs	HBe	rcDNA	cccDNA	α-HBs	α-HBe
Hagiwara et al[160]	Sim	Combi: 48 wk	4	60	62	85	-	60	77	38
Zhang et al[63]	Sim	Combi: 48 wk	9	-	58	-	-	30	73	-
	Mono	IFN: 48 wk	6	-	31	-	-	25	56	-
	Add	IFN: 12 wk; +Combi: 36 wk; +NA: 12 wk	16	-	72	-	-	50	78	-
	Add	IFN: 24 wk; +Combi: 24 wk; +NA: 24 wk	9	-	69	-	-	31	78	-
Huang et al[48]	Swi	NA: ≥ 2 yr +IFN: 60 wk	33	91	n.a.	-	26	65	n.a.	-
	Mono	NA: ≥ 2 yr	0	38	n.a.	-	0	22	n.a.	-
Zhou et al[49]	Swi	NA: ≥ 4 yr +IFN: 48 wk	36	n.a.	n.a.	-	27	n.a.	-	25
	Mono	NA: ≥ 5 yr	4	n.a.	n.a.	-	0	n.a.	-	58

HBV: Hepatitis B virus; rcDNA: Relaxed circular DNA; cccDNA: Covalently closed circular DNA; ALT: Alanine aminotransferase; NA: Nucleoside/nucleotide analogue; IFN: Interferon; n.a.: Not applicable; Sim: Simultaneous therapy; Add: Add-on therapy; Mono: Monotherapy; Swi: Switch therapy.