Interferon therapy reduces incidence of hepatocellular carcinoma in patients with high risk of hepatitis B virus-related hepatocellular carcinoma

doi:10.4251/wjgo.123962

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastrointest Oncol. Nov 15, 2026; 18(11): 123962
Published online Nov 15, 2026. doi: 10.4251/wjgo.123962

Table 1 Baseline characteristics of interferon and nucleos(t)ide analogs groups before and after propensity score matching, n (%)

Character	Before PSM				After PSM
Character	IFN group (n = 120)	NAs group (n = 248)	P value	SMD	IFN group (n = 71)	NAs group (n = 145)	P value	SMD
Sex	-	-	0.56	-	-	-	0.219	-
Female	29 (24.17)	67 (27.02)		-0.067	15 (21.13)	42 (28.97)	-	-0.175
Male	91 (75.83)	181 (72.98)		0.067	56 (78.87)	103 (71.03)	-	0.175
Age	-	-	0.359	-	-	-	0.68	-
Male < 40 years or female < 50 years	45 (37.50)	81 (32.66)	-	0.1	29 (40.85)	55 (37.93)	-	0.083
Male ≥ 40 years or female ≥ 50 years	75 (62.50)	167 (67.34)	-	-0.1	42 (59.15)	90 (62.07)	-	-0.083
Family history of HCC	-	-	0.005	-	-	-	0.622	-
No	103 (85.83)	180 (72.58)		0.38	56 (78.87)	110 (75.86)	-	0.058
Yes	17 (14.17)	68 (27.42)		-0.38	15 (21.13)	35 (24.14)	-	-0.058
Liver cirrhosis			< 0.001	-	-	-	0.267	-
Non-cirrhosis	80 (66.67)	103 (41.53)	-	0.533	39 (54.93)	68 (46.90)	-	0.164
Compensatory cirrhosis	40 (33.33)	145 (58.47)	-	-0.533	32 (45.07)	77 (53.10)	-	-0.164
Alpha-fetoprotein ≥ 7.0 ng/mL	-	-	< 0.001	-	-	-	0.288	-
No	101 (84.17)	127 (51.21)		0.903	53 (74.65)	98 (67.59)	-	0.144
Yes	19 (15.83)	121 (48.79)		-0.903	18 (25.35)	47 (32.41)	-	-0.144
Liver nodules detected on imaging	-	-	0.939	-	-	-	0.536	-
No	89 (74.17)	183 (73.79)	-	0.009	57 (80.28)	111 (76.55)	-	0.118
Yes	31 (25.83)	65 (26.21)	-	-0.009	14 (19.72)	34 (23.45)	-	-0.118
Diabetes	-	-	0.012	-	-	-	1	-
No	115 (95.83)	217 (87.50)	-	0.417	66 (92.96)	136 (93.79)	-	-0.04
Yes	5 (4.17)	31 (12.50)	-	-0.417	5 (7.04)	9 (6.21)	-	0.04
Alcohol intake	-	-	0.304	-	-	-	0.536	-
No	94 (78.33)	182 (73.39)		0.12	57 (80.28)	111 (76.55)	-	0.118
Yes	26 (21.67)	66 (26.61)		-0.12	14 (19.72)	34 (23.45)	-	-0.118
Fatty liver	-	-	0.823	-	-	-	0.633	-
No	105 (87.50)	219 (88.31)	-	-0.024	60 (84.51)	126 (86.90)	-	-0.078
Yes	15 (12.50)	29 (11.69)	-	0.024	11 (15.49)	19 (13.10)	-	0.078
Platelet count (× 10⁹/L)	174	134.5	< 0.001	0.826	163	149	0.103	0.252
Platelet count (× 10⁹/L)	(146.00, 209.25)	(89.00, 177.25)	< 0.001	0.826	(139.00, 197.50)	(108.00, 190.00)	0.103	0.252
HBsAg (IU/mL)	378.49	1440.72	< 0.001	-1.043	495.81	818.42	0.088	-0.262
HBsAg (IU/mL)	(87.61, 1013.48)	(559.95, 3118.72)	< 0.001	-1.043	(157.23, 1409.65)	(425.93, 2236.81)	0.088	-0.262
HBeAg	-	-	< 0.001	-	-	-	0.245	-
Negative	100 (83.33)	133 (53.63)		0.797	53 (74.65)	97 (66.90)	-	0.16
Positive	20 (16.67)	115 (46.37)		-0.797	18 (25.35)	48 (33.10)	-	-0.16
HBV DNA (lg IU/mL)	0.00 (0.00, 2.01)	2.90 (0.00, 5.30)	< 0.001	-1.045	0.00 (0.00, 2.43)	1.86 (0.00, 3.69)	0.081	-0.236

Serum hepatitis B virus DNA levels were measured and log10-transformed (expressed as lg IU/mL. PSM: Propensity score matching; NAs: Nucleos(t)ide analogs; IFN: Interferon; HCC: Hepatocellular carcinoma; HBeAg: Hepatitis B virus e antigen; HBV: Hepatitis B virus; SMD: Standardized mean difference; HBsAg: Hepatitis B surface antigen.

Full Size Table

Table 2 Cox regression analysis of hepatocellular carcinoma occurrence in patients with high risk of hepatitis B virus-associated hepatocellular carcinoma

Character	Univariate Cox regression		Multifactor Cox regression
Character	P value	HR (95%CI)	P value	HR (95%CI)
Sex
Male	-	1.00 (reference)	-	-
Female	0.073	1.77 (0.95–3.30)	-	-
Age
Male < 40 years or female < 50 years	-	1.00 (reference)	-	1.00 (reference)
Male ≥ 40 years or female ≥ 50 years	< 0.001	3.43 (1.70-6.92)	0.005	2.76 (1.35-5.61)
Family history of HCC
No	-	1.00 (reference)	-	1.00 (reference)
Yes	< 0.001	2.32 (1.43-3.75)	0.022	1.76 (1.09-2.86)
Liver cirrhosis
Non-cirrhosis	-	1.00 (reference)	-	1.00 (reference)
Compensatory cirrhosis	< 0.001	3.91 (2.21-6.93)	0.009	2.27 (1.23-4.19)
-fetoprotein ≥ 7.0 ng/mL
No	-	1.00 (reference)	-	-
Yes	0.748	1.08 (0.66-1.78)
Liver nodules detected on imaging
No	-	1.00 (reference)	-	-
Yes	0.389	1.26 (0.75-2.12)	-	-
Diabetes
No	-	1.00 (reference)	-	-
Yes	0.216	1.56 (0.77-3.14)	-	-
Alcohol intake
No	-	1.00 (reference)	-	-
Yes	0.728	1.10 (0.65-1.86)	-	-
Fatty liver
No	-	1.00 (reference)	-	-
Yes	0.995	0.00 (0.00-infinity)	-	-
Antiviral therapy
NAs treatment		1.00 (reference)		1.00 (reference)
Peg IFN-α treated with NAs alone or in combination	< 0.001	0.08 (0.02-0.25)	< 0.001	0.12 (0.04-0.39)
White blood cell count (× 10⁹/L)	0.835	0.98 (0.85-1.14)	-	-
Platelet count (× 10⁹/L)	< 0.001	0.99 (0.99-0.99)	0.279	1.00 (0.99-1.00)
Glutamic-pyruvic transaminase (IU/L)	0.518	1.00 (1.00-1.01)	-	-
Glutamic oxalacetic transaminase (IU/L)	0.213	1.00 (1.00-1.01)	-	-
Albumin (g/L)	0.576	1.01 (0.96-1.07)	-	-
Total bilirubin (μmol/L)	0.491	1.01 (0.98-1.04)	-	-
Alkaline phosphatase (IU/L)	0.391	1.00 (1.00-1.01)	-	-
Glutamyltranspeptidase (U/L)	0.856	1.00 (1.00-1.00)	-	-
HBsAg (IU/mL)	0.131	1.00 (1.00-1.00)	-	-
HBV DNA (lg IU/mL)	0.477	0.97 (0.88-1.06)	-	-
HBeAg
Negative	-	1.00 (reference)	-	-
Positive	0.410	0.81 (0.48-1.35)	-	-
Abdominal lymph node enlargement
No	-	1.00 (reference)	-	-
Yes	0.610	1.30 (0.47-3.57)	-	-

HR: Hazard ratio; CI: Confidence interval; HCC: Hepatocellular carcinoma; IFN: Interferon; NAs: Nucleos(t)ide analogs; HBeAg: Hepatitis B virus e antigen; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen.

Full Size Table

Citation: Hao M, Liu CR, Zhang M, Zhou XQ, Jiang ZC, Gao XH, Zhang X, Wang WJ, Wang YK, Jia XL, Li YP, Dang SS. Interferon therapy reduces incidence of hepatocellular carcinoma in patients with high risk of hepatitis B virus-related hepatocellular carcinoma. World J Gastrointest Oncol 2026; 18(11): 123962
URL: https://www.wjgnet.com/1948-5204/full/v18/i11/123962.htm
DOI: https://dx.doi.org/10.4251/wjgo.123962

Hao M, Liu CR, Zhang M, Zhou XQ, Jiang ZC, Gao XH, Zhang X, Wang WJ, Wang YK, Jia XL, Li YP, Dang SS. Interferon therapy reduces incidence of hepatocellular carcinoma in patients with high risk of hepatitis B virus-related hepatocellular carcinoma. World J Gastrointest Oncol 2026; 18(11): 123962 [DOI: 10.4251/wjgo.123962]

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