Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens

Table 1 Clinical characteristics of the patients, n (%)

Characteristics	Total patients (n = 121)	Sustained HBsAg seroclearance (n = 105)	HBV reversion (n = 16)	P value
Age, years, mean ± SD	35.6 ± 10.9	36.2 ± 11.2	31.8 ± 8.0	0.132
Male	74 (61.2)	66 (62.9)	8 (50.0)	0.326
Family history of HBV infection	64 (52.9)	57 (54.28)	7 (43.8)	0.432
Characteristics before HBsAg seroclearance
Therapy regimens
IHCs treated with peg-IFN-α alone	73 (60.3)	66 (62.9)	7 (43.8)	0.342
CHB treated with NA sequential combination with peg-IFN-α	42 (34.7)	34 (32.4)	8 (50.0)
CHB treated with NA de novo combination with peg-IFN-α	6 (5.0)	5 (4.7)	1 (6.2)
Peg-IFN-α types
Peg-IFN-α-2a	41 (33.9)	34 (32.4)	7 (43.8)	0.371
Peg-IFN-α-2b	80 (66.1)	71 (67.6)	9 (56.3)
HBsAg levels at the initiation of peg-IFN-α, log10 IU/mL, IQR	85.6 (4.5, 362.4)	71.4 (3.7, 289.4)	497.4 (12.7, 1354.5)	0.078
HBsAb status
HBsAb negative	113 (93.4)	98 (93.3)	15 (93.8)	1.000
HBsAb positive	8 (6.6)	7 (6.7)	1 (6.3)
HBV DNA negative	84 (69.4)	75 (71.4)	9 (56.3)	0.250
HBV DNA positive	37 (30.6)	30 (28.6)	7 (43.8)
HBeAg negative	101 (83.5)	87 (82.9)	14 (87.5)	1.000
HBeAg positive	20 (16.5)	18 (17.1)	2 (12.5)
Treatment time before HBsAg loss, weeks, IQR	20.0 (12.0, 42.0)	20.0 (12.0, 38.0)	40.0 (12.0, 57.0)	0.212
Consolidation time after HBsAg loss, weeks, IQR	12.0 (12.0, 24.0)	12.0 (12.0, 24.0)	6.0 (0.0, 11.0)	< 0.001
Total Duration of peg-IFN-α, weeks, IQR	44.0 (28.0, 56.0)	40.0 (28.0, 55.0)	46.0 (29.0, 62.0)	0.625
Characteristics at the cessation of peg-IFN-α
Patients with HBsAg seroconversion	79 (65.3)	74 (70.5)	5 (31.3)	0.074
HBsAb levels, mIU/mL, IQR	36.9 (9.6, 115.1)	44.3 (9.9, 141.0)	9.1 (3.9, 16.3)	< 0.001
HBeAg negative	121 (100.0)	105 (100.0)	16 (100.0)	-
HBV DNA negative	121 (100.0)	105 (100.0)	16 (100.0)	-
ALT, IU/L, IQR	38.0 (24.0, 64.0)	38.0 (23.9, 60.0)	40.0 (26.3, 96.0)	0.218
FibroScan value, kPa, mean ± SD	5.7 ± 1.0	5.7 ± 1.0	6.0 ± 1.0	0.314

HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; IHCs: Inactive HBsAg carriers; CHB: Chronic hepatitis B; Peg-IFN-α: Peginterferon alpha; NA: Nucleos (t)ide analog; HBeAg: Hepatitis B e antigen; HBV DNA: Hepatitis B virus-deoxyribonucleic acid; ALT: Alanine aminotransferase; AST: Aspartate transaminase; IQR: Interquartile range.

Table 2 Univariate logistic regression analysis of the predictors of hepatitis B surface antigen recurrence

Characteristics	OR	95%CI	P value
Age (years)	0.962	(0.916-1.012)	0.133
Gender	1.692	(0.588-4.870)	0.329
Family history of HBV infection	0.655	(0.227-1.890)	0.434
Characteristics at the initiation of peg-IFN-α
HBsAg level, IU/mL	1.000	(1.000-1.000)	0.398
HBsAb negative	0.933	(0.107-8.130)	0.950
HBV DNA positive	0.514	(0.176-1.506)	0.225
HBeAg positive	1.448	(0.302-6.934)	0.643
Peg-IFN-α-2a	1.624	(0.558-4.730)	0.374
Peg-IFN-α monotherapy	0.588	(0.224-1.546)	0.282
Treatment time of peg-IFN-α (weeks)	1.014	(0.992-1.035)	0.217
Total duration of peg-IFN-α (weeks)	0.999	(0.975-1.024)	0.9570
Consolidation time < 12 weeks	25.636	(7.039-93.356)	< 0.001
Characteristics at the cessation of peg-IFN-α
Without HBsAg seroconversion	5.252	(1.684-16.376)	0.004
HBsAb, mIU/mL	0.952	(0.914-0.992)	0.018
HBsAb < 35.3 mIU/mL	9.705	(2.098-44.883)	0.004
HBsAb disappeared during the follow-up	14.500	(1.513-138.972)	0.020
ALT level at baseline, IU/L	1.011	(1.001-1.021)	0.127
FibroScan values at baseline (kPa)	1.314	(0.791-2.183)	0.292

HBV: Hepatitis B virus; Peg-IFN-α: Peginterferon alpha; HBsAg: Hepatitis B surface antigen; HBsAb: Hepatitis B surface antibody; ALT: Alanine aminotransferase; OR: Odds ratio.

Table 3 Multivariate logistic regression analysis of predictors of hepatitis B surface antigen recurrence

Characteristics	OR	95%CI	P value
Age (years)	0.924	(0.843-1.012)	0.089
Gender	0.665	(0.140-3.169)	0.609
Peg-IFN-α-2a	0.759	(0.165-3.485)	0.723
Without HBsAg seroconversion	9.388	(0.512-172.212)	0.131
HBsAb < 35.3 mIU/mL	3.449	(0.264-45.112)	0.345
Consolidation time < 12 weeks	28.044	(4.525-173.791)	< 0.001
HBsAb disappeared during the follow-up	46.445	(2.571-838.957)	0.009

Peg-IFN-α: Peginterferon alpha; HBsAg: Hepatitis B surface antigen; HBsAb: Hepatitis B surface antibody; OR: Odds ratio.