Retreatment hepatitis B surface antigen clearance prediction model identifies pegylated interferon alpha candidates in chronic hepatitis B

Table 2 Univariate Cox regression, least absolute shrinkage and selection operator regression, and multivariate Cox regression analysis of factors associated with hepatitis B surface antigen seroclearance in patients with chronic hepatitis B receiving pegylated interferon alpha-2b retreatment

Characteristic	Univariable		LASSO	Multivariable
	HR (95%CI)	P value		HR (95%CI)	P value
Age (years)	0.979 (0.931-1.030)	0.406
Gender
Male	1
Female	1.185 (0.522-2.690)	0.685
BMI (kg/m2)	0.945 (0.837-1.067)	0.363
HBV family history
No	1
Yes	0.642 (0.301-1.373)	0.254
Smoke history
No	1
Yes	0.785 (0.208-2.968)	0.722
Drink history
No	1
Yes	0.562 (0.072-4.393)	0.583
Diabetes mellitus
No	1
Yes	0.742 (0.100-5.482)	0.770
Hypertension
No	1
Yes	1.444 (0.497-4.194)	0.499
Cirrhosis
No	1
Yes	0.662 (0.252-1.742)	0.404
First circle Peg-IFNα treatment relative
Combination of NAs			Yes		0.022
No	1			1
Yes	0.159 (0.064-0.394)	< 0.001		0.276 (0.092-0.833)
Type of NAs
No	1
ETV	0.056 (0.011-0.280)	< 0.001
TDF	0.198 (0.072-0.546)	0.002
TAF	0.188 (0.065-0.544)	0.002
Combine	0.187 (0.038-0.933)	0.041
1st Peg-IFNα treatment course (weeks)	1.011 (0.986-1.037)	0.394
Baseline HBsAg level of initial treatment (log10 IU/mL)	0.472 (0.324-0.686)	< 0.001
HBsAg level at week 12 of initial treatment (log10 IU/mL)	0.433 (0.329-0.569)	< 0.001
HBsAg level at end of initial treatment (log10 IU/mL)	0.474 (0.377-0.594)	< 0.001	Yes	1.024 (0.641-1.638)	0.920
HBsAg decline at week 12 of initial treatment (log10 IU/mL)	4.043 (2.576-6.343)	< 0.001	Yes	1.113 (0.578-2.142)	0.310
HBsAg decline at end of initial treatment (log10 IU/mL)	2.450 (1.748-3.434)	< 0.001	Yes	2.050 (1.108-3.793)	0.028
HBsAg decline at end of initial treatment (%)	27.448 (3.286-29.246)	0.002
HBeAg
Negative	1
Positive	0.706 (0.285-1.749)	0.452
HBV DNA (log10 IU/mL)	1.047 (0.954-1.148)	0.333
ALT (U/L)	1.001 (0.999-1.003)	0.266
AST (U/L)	0.997 (0.989-1.005)	0.501
GGT (U/L)	1.000 (0.994-1.006)	0.965
TBIL (μmol/L)	0.989 (0.941-1.040)	0.670
ALB (g/L)	1.063 (0.921-1.227)	0.405
PLT (109/L)	0.998 (0.990-1.006)	0.643
AFP (ng/mL)	0.966 (0.885-1.055)	0.441
LSM (kPa)	0.919 (0.798-1.059)	0.244
CAP (dB/m)	0.994 (0.987-1.001)	0.109
The interval weeks between the two treatments (weeks)	1.010 (1.006-1.014)	< 0.001	Yes	1.013 (1.008-1.018)	< 0.001
Second circle Peg-IFNα treatment relative
HBsAg level at retreatment baseline (log10 IU/mL)	0.440 (0.353-0.549)	< 0.001	Yes	0.571 (0.410-0.795)	0.001
Rebound magnitude of HBsAg at retreatment baseline compared to end of initial treatment (log10 IU/mL)	0.757 (0.658-0.872)	< 0.001
Rebound magnitude of HBsAg at retreatment baseline compared to end of initial treatment (%)	0.682 (0.448-1.037)	0.073
Rebound magnitude of HBsAg at retreatment baseline compared to baseline of initial treatment (%)	0.179 (0.107-0.300)	< 0.001
Model parameter			λ = 0.054

LASSO: Least absolute shrinkage and selection operator; HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; HBV: Hepatitis B virus; Peg-IFNα: Pegylated interferon alpha; NAs: Nucleoside analogs; ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; TAF: Tenofovir alafenamide fumarate tablets; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B envelope antigen; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; TBIL: Total bilirubin; ALB: Albumin; PLT: Platelet; AFP: Alpha-fetoprotein; LSM: Liver stiffness measurement; CAP: Controlled attenuation parameter.