Current and future directions for treating hepatitis B virus infection

Table 1 Treatment efficacy at 24 wk after the end of peginterferon treatment in hepatitis B e antigen-positive chronic hepatitis B

Ref.	No. of patients	Formula of therapy	Seroconversion from HBeAg to anti-HBe (%)	Suppression of HBV DNA (%)	Normalization of ALT (%)	HBsAg loss (n)
Cooksley et al[27]	51	IFNα-2a 4.5 MIU three times weekly for 24 wk	25	25a	26	0
	49	Peg-IFNα-2a 90 μg weekly for 24 wk	37	43a	43	0
	46	Peg-IFNα-2a 180 μg weekly for 24 wk	35	39a	35	0
	48	Peg-IFNα-2a 270 μg weekly for 24 wk	27	27a	31	0
Lau et al[28]	214	Peg-IFNα-2a 180 μg weekly plus placebo for 48 wk	32	32b	41	8
	271	Peg-IFNα-2a 180 μg weekly plus LAM 100 mg daily for 48 wk	27	34b	39	8
	272	LAM 100 mg/d for 48 wk	19	22b	28	0
Chan et al[29]	50	Peg-IFNα-2b 1.5 μg/kg weekly for 32 wk plus LAM 100 mg daily for 52 wk	36	36a	50	1
	50	LAM 100 mg daily for 52 wk	14	14a	30	0
Liaw et al[30]	140	Peg-IFNα-2a 90 μg weekly for 24 wk	14	21c	30	1
	136	Peg-IFN α-2a 180 μg weekly for 24 wk	22	21c	30	0
	136	Peg-IFNα-2a 90 μg weekly for 48 wk	25	32c	43	3
	136	Peg-IFNα-2a 180 μg weekly for 48 wk	36	42c	52	3

a < 500000 copies/mL; b < 100000 copies/mL; c < 20000 copies/mL. LAM: Lamivudine; Peg-IFN: Peginterferon; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; Anti-HBe: Antibody to HBe antigen; ALT: Alanine aminotransferase.

Table 2 Long-term treatment efficacy of peginterferon treatment in hepatitis B e antigen-positive chronic hepatitis B

Ref.	No. of patients	Formula of therapy	Seroconversion from HBeAg to anti-HBe (%)	Suppression of HBV DNA (%)	Normalization of ALT (%)	HBsAg loss (n)
cBuster et al[31]	91	Peg-IFNα-2b for 52 wk	35	25a	30	7 (8%)
	81	Peg-IFNα-2b plus LAM for 52 wk	25	31a	30	12 (15%)
dWong et al[32]	85	Peg-IFNα-2b for 32 wk plus LAM for 52 or 104 wk	60	13b	57	2 (2.4%)

a < 10000 copies/mL; b < 100 copies/mL. The treatment efficacies were assessed at approximately 3-year follow-up^c or approximately 5-year follow-up^d. LAM: Lamivudine; Peg-IFN: Peginterferon; HBeAg: Hepatitis B e antigen; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; ALT: Alanine aminotransferase.

Table 3 Treatment efficacy of peginterferon treatment in hepatitis B e antigen-negative chronic hepatitis B

Ref.	No. of patients	Therapy regimen	HBV DNA suppression (%)	ALT normalization (%)	HBsAg loss (n)
cMarcellin et al[33]	177	Peg-IFNα-2a 180 μg weekly plus placebo for 48 wk	43a	59	7
	179	Peg-IFNα-2a 180 μg weekly plus LAM 100 mg daily for 48 wk	44a	60	5
	181	LAM 100 mg daily for 48 wk	29a	44	0
cPapadopoulos et al[34]	88	Peg-IFNα-2b 1.5 μg/kg weekly plus LAM 100 mg daily for 48 wk	59 (60 IU/mL below)	27	NA
	35	Peg-IFNα-2b 1.5 μg/kg weekly for 48 wk	42	40	NA
dMarcellin et al[35]	116	Peg-IFNα-2a 180 μg weekly plus placebo for 48 wk	28b	31	9 (8%)
	114	Peg-IFNα-2a 180 μg daily plus LAM 100 mg daily for 48 wk	25b	31	9 (8%)
	85	LAM 100 mg daily for 48 wk	15b	18	0 (0%)

a < 20000 copies/mL; b < 10000 copies/mL. The treatment efficacies were assessed at 24-wk follow-up^c or approximately 3-year follow-up^d. LAM: Lamivudine; Peg-IFN: Peginterferon; ALT: Alanine aminotransferase; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; NA: Not available.

Table 4 Treatment efficacy of entecavir in chronic hepatitis B

Ref.	No. of patients	HBeAg	Therapy regimen	HBeAg loss (%)/seroconversion from HBeAg to anti-HBe (%)	Undetectable of HBV DNA (%)	Normalization of ALT (%)	HBsAg loss (n)
1Chang et al[66]	354 NUCs - treatment-naive	Positive	ETV 0.5 mg daily for 48 wk	22/21	67	68	6
	355 NUCs - treatment-naive	Positive	LAM 100 mg daily for 48 wk	20/18	36	60	4
2Gish et al[67]	243 NUCs - treatment-naive	Positive	ETV 0.5 mg daily for 2 yr	NA/31	80	87	18
	164 NUCs - treatment-naive	Positive	LAM 100 mg daily for 2 yr	NA/26	39	79	10
1Lai et al[70]	296	Negative	ETV 0.5 mg daily for 48 wk	NA/NA	90	78	1
	287	Negative	LAM 100 mg daily for 48 wk	NA/NA	72	71	1

Treatment efficacies were assessed at 48 wk¹, or 2 years². ETV: Entecavir; NUCs: Nucleos(t)ide analogues; NA: Not available; LAM: Lamivudine; HBeAg: Hepatitis B e antigen; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; HBsAg: Hepatitis B surface antigen; Anti-HBe: Antibody to HBe antigen.

Table 5 Treatment efficacy of tenofovir in chronic hepatitis B

Ref.	No. of patients	HBeAg	Therapy regimen	HBeAg loss (%)/seroconversion from HBeAg to anti-HBe (%)	Undetectable of HBV DNA (%)	Normalization of ALT (%)	HBsAg loss (n)
1Marcellin et al[83]	176 NUCs - treatment-naive	Positive	TDF 300 mg daily (> 48 wk)	NA/21	76	68	5
	90	Positive	ADF 10 mg daily (> 48 wk)	NA/18	13	54	0
	90	Positive	ADF (48 wk)	NA/18	13	54	0
	125	Negative	ADF (48 wk)	NA/NA	63	77	0
2Heathcote et al[88]	266	Positive	TDF (> 144 wk)	34/26	71	74	20
	365	Negative	TDF (> 144 wk)	NA/NA	87	81	0
2Marcellin et al[91]	266	Positive	TDF (> 240 wk)	49/40	65	73	10
	375	Negative	TDF (> 240 wk)	NA/NA	83	85	1

The treatment efficacies were assessed at 48 wk¹, or 144 wk². TDF: Tenofovir; ADF: Adefovir; NA: Not available; HBeAg: Hepatitis B e antigen; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; HBsAg: Hepatitis B s antigen; Anti-HBe: Antibody to HBe antigen.

Table 6 Summary of current and future treatments for hepatitis B virus infection

Current treatments for HBV

Peginterferon therapy

NUCs

Entecavir

Tenofovir disoproxil fumarate (tenofovir)

Future treatments for HBV

NUCs

Tenofovir alafenamide

Treatments for HBV cccDNA

Entry inhibitors targeting of sodium taurocholate cotransporting polypeptide

NUCs: Nucleos(t)ide analogues; HBV: Hepatitis B virus; cccDNA: Covalently closed circular DNA.