Short- and long-term outcome of interferon therapy for chronic hepatitis B infection

Table 1 Summary of the studies of the response to interferon-based treatment on hepatitis B virus genotypes

Ref.	Study type	Number ofpatients(treated/controls)	IFN	Region of origin	HBeAg-positive (%)	Treatment endpoint	Treatment endpoint by HBV genotype (%)	Significance(P value)
Wai et al[26]	Retrospective, unmatched controls	107 (73/34)	IFN α	China	100.0	HBeAg seroconversion	B: 39 C: 17	0.03
Kao et al[27]	Retrospective, unmatched controls	58 (58/0)	IFN α	Taiwan	100.0	Loss of HBeAg and HBV DNA 48 wk post-treatment	B: 41 C: 15	0.045
Zhang et al[28]	Retrospective, unmatched controls	35 (35/0)	IFN α	France	0.0	Normalization of ALT, loss of HBV DNA by a branched-DNA assay 6 mo post-treatment	A: 70 non-A: 40	0.001
Erhardt et al[29]	Retrospective, unmatched controls	165 (69/72)	IFN α	Germany, Mediterranean, Eastern Europe, Asia, Africa	A: 51.4 B: 5	HBeAg-positive: normalization of ALT, negative HBV DNA by a hybridization assay, and HBeAg seroconversion 6 mo post-treatment HBeAg-negative: loss of HBV DNA by a hybridization assay and the normalization of ALT 6 mo post-treatment	(overall) A: 49 D: 26	0.005
					C: 8.4 D: 31.9		(HBeAg-positive) A: 46 D: 24	0.03
					E: 2.5 G: 0.8		(HBeAg-negative) A: 59 D: 29	0.05
Flink et al[30]	Prospective, multicenter randomized controlled trials	266 (266/0)	Peg- IFN-α-2b +/- lamivudine	The Netherlands	100.0	Loss of HBsAg at the end of follow-up	A: 14 B: 9 C: 3 D: 2	0.006
Erhardt et al[32]	Retrospective, cohort	49 (23/26)	IFN α	Germany, Hong Kong, France	E: 47 F: 50 G: 50 H: 60	Normalization of ALT, decrease of HBV DNA < 4000IU/mL 6 mo post-treatment	E: 36 F: 50 G: 20 H: 50	NA

IFN: Interferon; HBeAg: Hepatitis e antigen; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; NS: Not significant; NA: Not available.

Table 2 Summary of the long-term follow-up studies of interferon-α treatment on hepatitis B virus-related liver disease progression

Ref.	Study type	Number of patients (treated/controls)	Region of origin	HBeAg-positive	Treatment follow-up (yr)	Cirrhosis development (% treated vs % controls)	Significance (P value)	Cirrhosis complication development (% treated vs % controls)	Significance (P value)
Lin et al[19]	Prospective, randomized, controlled	89 (60/29)	Taiwan	100%	7.4	13.3 vs 17.2	NS	9.0 vs 14.7	NS
Lin et al[42]	Retrospective, matched controls	466 (233/233)	Taiwan	100%	6.8	17.8 vs 33.7	0.041	NA	NA
Krogsgaard et al[43]	Retrospective, multicenter controlled trials	253 (histologically evaluated)	Europe	100%	4.7	10 vs 10	NS	NA	NA
Tangkijvanich et al[44]	Retrospective, unmatched controls	139 (69/72)	Thailand	100%	5.0	10.4 vs 22.2	NS	NA	NA
Truong et al[46]	Retrospective, matched controls	62 (27/35)	Japan	59.6%	6.5	11 vs 6	NS	NA	NA
Yuen et al[47]	Prospective, matched controls	411 (208/203)	Hong Kong	100%	8.9	NA	NA	4.3 vs 1.0	0.062

HBeAg: Hepatitis e antigen; NS: Not significant; NA: Not available.

Table 3 Summary of the long-term follow-up studies of interferon α treatment on the development of hepatitis B virus-related hepatocellular carcinoma

Ref.	Study type	Number of patients (treated/controls)	Region of origin	HBeAg-positive (%)	Cirrhosis (%)	Treatment follow-up (yr)	HCC development (% treated vs % controls)	Significance(P value)
Lin et al[19]	Prospective, randomized, controlled	101 (67/34)	Taiwan	100	12.5	7.4	1.5 vs 11.8	0.043
Lin et al[42]	Retrospective, matched controls	466 (233/233)	Taiwan	100	9.4	6.8	2.7 vs 12.5	0.011
Ikeda et al[49]	Retrospective, unmatched controls	313 (94/219)	Japan	36	100	6.9	17.0 vs 30.8	0.012
Krogsgaard et al[43]	Retrospective, multicenter controlled trials	308 (210/98)	Europe	100	6.1	4.7	0.96 vs 1.0	NS
International IFN-α HCC Study Group[50]	Retrospective, multicenter, matched controls	146 (49/97)	Italy, Argentina	NA	91	6.5	16 vs 19	NS
Mazzella et al[51]	Prospective, randomized, controlled	64 (33/ 31)	Italy	0	0	6.9	3.0 vs 6.4	NS
Tangkijvanich et al[44]	Retrospective, unmatched controls	139 (69/72)	Thailand	100	20.1	5.0	4.7 vs 12.5	NS
Papatheodoridis et al[45]	Retrospective, unmatched controls	404 (209/195)	Greece	100	30.9	6.0	8.1 vs 7.7	NS
Truong et al[46]	Retrospective, matched controls	62 (27/35)	Japan	59.6	1.6	6.5	3.7 vs 0.0	NS
Yuen et al[47]	Prospective, matched controls	411 (208/203)	Hong Kong	100	NA	8.9	2.4 vs 0.0	NS
			Number of analyzed studies	RD/RR			95%CI	Significance (P value)
Cammà et al[52]	Meta-analysis	853/652	7 Studies	RD = -6.4% (overall)			-2.8%-(-10%)	< 0.001
				RD = -4.8% (European)			-11.1%-1.5%	NS
Miyake et al[53]	Meta-analysis	553/750	8 Studies	RD = -5.0% (overall)			-9.4%-(-0.5%)	0.028
				RD = -8.5% (Asian)			-13.6-(-3.6%)	0.001
Sung et al[54]	Meta-analysis	1292/1458	12 Studies	RR = 0.66			0.48-0.89	0.006
Yang et al[55]	Meta-analysis	1006/1076	11 Studies	RR = 0.59			0.43-0.81	0.001
Zhang et al[56]	Meta-analysis	176/171	2 Studies	RR = 0.23			0.05-1.04	NS
Jin et al[57]	Meta-analysis	1291/1048	9 Studies	RR = 0.274			0.059-1.031	NS

IFN: Interferon; HBeAg: Hepatitis e antigen; HCC: Hepatocellular carcinoma; NS: Not significant; NA: Not available; RD: Risk difference; RR: Relative risk.