Baseline hepatitis B surface antigen and cirrhosis predict extended interferon therapy in chronic hepatitis B: A retrospective study

Table 1 Clinical characteristics of the study population, mean ± SD/n (%)

Characteristic	Before PSM				After PSM
	Overall (n = 688)	Training cohort (n = 274)	Validation cohort (n = 414)	P value	Overall (n = 375)	Training cohort (n = 196)	Validation cohort (n = 179)	P value
Age (year)	40.82 ± 9.19	41.38 ± 8.69	40.44 ± 9.49	0.189	40.91 ± 8.91	41.15 ± 7.88	40.65 ± 9.94	0.588
Gender				0.790				0.805
Male	421 (61.19)	166 (60.58)	255 (61.59)		228 (60.80)	118 (60.20)	110 (61.45)
Female	267 (38.81)	108 (39.42)	159 (38.41)		147 (39.20)	78 (39.80)	69 (38.55)
Cirrhosis				0.085				0.135
(-)	594 (89.32)	238 (86.86)	356 (91.05)		333 (89.04)	170 (86.73)	163 (91.57)
(+)	71 (10.68)	36 (13.14)	35 (8.95)		41 (10.96)	26 (13.27)	15 (8.43)
IFN treatment course (week)				0.673				0.988
Median (Q1, Q3)	24.36 (15.00, 40.71)	24.00 (16.00, 42.00)	25.00 (15.00, 39.71)		24.14 (15.00, 40.00)	24.00 (16.00, 39.25)	24.86 (14.14, 40.71)
	32.0 ± 23.15	32.54 ± 23.68	31.77 ± 22.82		31.82 ± 22.35	31.83 ± 23.02	31.80 ± 21.67
IFN group				0.550				0.487
< 48	555 (80.67)	218 (79.56)	337 (81.40)		301 (80.27)	160 (81.63)	141 (78.77)
≥ 48	133 (19.33)	56 (20.44)	77 (18.60)		74 (19.73)	36 (18.37)	38 (21.23)
HBeAg				0.001				0.417
(-)	590 (86.64)	247 (91.82)	343 (83.25)		338 (90.13)	179 (91.33)	159 (88.83)
(+)	91 (13.36)	22 (8.18)	69 (16.75)		37 (9.87)	17 (8.67)	20 (11.17)
HBV DNA (log10 copies/mL)	1.66 ± 1.80	1.39 ± 1.93	1.88 ± 1.66	0.001	1.78 ± 1.69	1.65 ± 1.85	1.92 ± 1.48	0.123
HBsAg (IU/mL), median (Q1, Q3)	44.25 (3.39, 334.78)	37.08 (2.91, 401.76)	52.35 (3.95, 314.81)	0.755	49.54 (4.54, 330.75)	47.80 (5.56, 469.24)	51.78 (3.99, 235.90)	0.943
HBsAg (log10 IU/mL)	1.53 ± 1.31	1.51 ± 1.27	1.55 ± 1.34	0.687	1.56 ± 1.29	1.61 ± 1.28	1.50 ± 1.30	0.412
12-week HBsAg (log10 IU/mL), median (Q1, Q3)	-0.30 (-1.68, 1.28)	-0.26 (-1.51, 1.37)	-0.30 (-1.96, 1.15)	0.270	-0.29 (-1.51, 1.23)	-0.24 (-1.51, 1.37)	-0.30 (-1.82, 0.72)	0.246
HBsAg decline at 12 weeks (log10 IU/mL), median (Q1, Q3)	1.46 (0.51, 2.74)	1.42 (0.51, 2.55)	1.51 (0.53, 2.87)	0.156	1.46 (0.60, 2.80)	1.58 (0.59, 2.72)	1.43 (0.62, 2.90)	0.485
ALT (U/L), median (Q1, Q3)	24.00 (16.00, 41.00)	23.30 (15.00, 36.00)	24.55 (17.00, 42.85)	0.236	24.00 (16.45, 39.00)	24.00 (15.93, 37.38)	23.00 (17.00, 40.50)	0.298
TBiL (μmol/L)	16.19 ± 10.87	16.70 ± 10.35	15.87 ± 11.19	0.331	16.60 ± 11.46	16.79 ± 10.60	16.41 ± 12.35	0.749
ALP (U/L)	77.30 ± 31.11	72.88 ± 31.03	80.67 ± 30.78	0.002	76.25 ± 32.06	74.46 ± 33.45	78.21 ± 30.44	0.258
GGT (U/L), median (Q1, Q3)	21.00 (14.00, 34.00)	20.00 (14.00, 30.00)	22.00 (15.00, 35.00)	0.807	21.00 (14.00, 34.50)	21.50 (14.00, 32.25)	21.00 (15.00, 36.00)	0.557
ALB				0.067				0.486
< 40	637 (95.50)	255 (97.33)	382 (94.32)		359 (95.73)	189 (96.43)	170 (94.97)
≥ 40	30 (4.50)	7 (2.67)	23 (5.68)		16 (4.27)	7 (3.57)	9 (5.03)
WBC (109/L), median (Q1, Q3)	5.39 (4.30, 6.55)	5.51 (4.72, 6.66)	5.28 (4.20, 6.52)	0.155	5.43 (4.43, 6.50)	5.51 (4.57, 6.66)	5.30 (4.40, 6.47)	0.730
HB (g/L)	146.18 ± 21.76	146.02 ± 25.34	146.28 ± 19.13	0.880	145.50 ± 23.51	146.28 ± 26.96	144.64 ± 19.07	0.502
PLT (109/L)	208.52 ± 67.10	222.42 ± 66.80	199.51 ± 65.83	< 0.001	211.83 ± 60.98	215.57 ± 57.89	207.73 ± 64.10	0.214

PSM: Propensity score matching; IFN: Interferon; Q1: 1st quartile; Q3: 3st quartile; HBeAg: Hepatitis B envelope antigen; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; ALT: Alanine aminotransferase; TBiL: Total bilirubin; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; ALB: Albumin; WBC: White blood cell; HB: Hemoglobin; PLT: Platelet.

Table 2 Baseline characteristics of subgroups based on the duration of pegylated interferon α-2b therapy in the training cohort, mean ± SD/n (%)

Characteristic	Overall (n = 196)	The regular course (< 48 weeks) (n = 160)	The extended course (≥ 48 weeks) (n = 36)	P value
Age (year)	41.15 ± 7.88	41.69 ± 8.01	38.72 ± 6.82	0.041
Gender				0.800
Male	118 (60.20)	97 (60.62)	21 (58.33)
Female	78 (39.80)	63 (39.38)	15 (41.67)
Treatment regimen				0.420
IFN monotherapy	99 (50.51)	83 (51.88)	16 (44.44)
Combined with ETV	97 (49.49)	77 (48.12)	20 (55.56)
Cirrhosis				0.004
(-)	170 (86.73)	144 (90.00)	26 (72.22)
(+)	26 (13.27)	16 (10.00)	10 (27.78)
HBeAg				0.059
(-)	179 (91.33)	149 (93.12)	30 (83.33)
(+)	17 (8.67)	11 (6.88)	6 (16.67)
HBV DNA (log10 copies/mL)	1.65 ± 1.85	1.63 ± 1.72	1.74 ± 2.39	0.765
HBsAg (IU/mL), median (Q1, Q3)	47.80 (5.56, 469.24)	27.05 (2.50, 230.15)	60.19 (60.39, 1878.06)	0.002
HBsAg (log10 IU/mL)	1.61 ± 1.28	1.35 ± 1.20	2.75 ± 0.97	< 0.001
12-week HBsAg (log10 IU/mL), median (Q1, Q3)	-0.24 (-1.51, 1.37)	-0.47 (-1.68, 0.83)	1.94 (0.36, 2.75)	< 0.001
HBsAg decline at 12 weeks (log10 IU/mL), median (Q1, Q3)	1.58 (0.59, 2.72)	1.68 (0.72, 2.72)	0.75 (0.16, 2.60)	0.240
ALT (U/L), median (Q1, Q3)	24.00 (15.93 37.38)	24.00 (15.38, 35.60)	25.50 (20.35, 44.58)	0.681
TBiL (μmol/L)	16.79 ± 10.60	17.02 ± 11.25	15.75 ± 7.09	0.518
ALP (U/L)	74.46 ± 33.45	75.22 ± 35.56	71.08 ± 21.78	0.504
GGT (U/L), median (Q1, Q3)	21.50 (14.00, 32.25)	21.50 (14.00, 33.25)	21.50 (14.75, 28.25)	0.682
ALB				0.776
< 40	189 (96.43)	154 (96.25)	35 (97.22)
≥ 40	7 (3.57)	6 (3.75)	1 (2.78)
WBC (109/L), median (Q1, Q3)	5.51 (4.57, 6.66)	5.46 (4.36, 6.66)	5.63 (4.94, 6.48)	0.918
HB (g/L)	146.28 ± 26.96	146.54 ± 26.68	145.09 ± 28.53	0.771
PLT (109/L)	215.57 ± 57.89	216.75 ± 60.08	210.33 ± 47.33	0.549

Q1: 1st quartile; Q3: 3st quartile; IFN: Interferon; ETV: Entecavir; HBeAg: Hepatitis B envelope antigen; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; ALT: Alanine aminotransferase; TBiL: Total bilirubin; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; ALB: Albumin; WBC: White blood cell; HB: Hemoglobin; PLT: Platelet.

Table 3 Multiple least absolute shrinkage and selection operator-logistic regression analysis of factors associated with pegylated interferon α-2b treatment course in the training cohort

Characteristic	β	SE	Z value	P value	OR (95%CI)
Intercept	-2.04	1.36	-1.50	0.133	0.13 (0.01-1.87)
Age (years)	-0.05	0.03	-1.50	0.133	0.95 (0.90-1.01)
Baseline HBsAg (log10 IU/mL)	0.98	0.27	3.58	< 0.001	2.66 (1.56-4.53)
12-week HBsAg (log10 IU/mL)	0.26	0.14	1.91	0.056	1.30 (0.99-1.70)
Cirrhosis
(-)					1.00
(+)	1.25	0.59	2.13	0.033	3.48 (1.10-10.99)

Multifactorial logistic regression analysis revealed that an elevated baseline hepatitis B surface antigen level [odds ratio (OR) = 2.66, 95% confidence interval (CI): 1.56-4.53] and the presence of cirrhosis (OR = 3.48, 95%CI: 1.10-10.99) were independent risk factors. Z statistic: The larger the Z value, the more significant the effect of the independent variable on the dependent variable. OR: Odds ratio; CI: Confidence interval; Intercept: Constant; HBsAg: Hepatitis B surface antigen; 12-week HBsAg: Hepatitis B surface antigen at the 12^th week of treatment.