Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine

Table 1 Patient demographics and disease characteristics n (%)

Baseline	ETV (n = 159)	LAM (n = 146)
Age, mean ± SE, yr (range)	35 ± 1.1 (17-76)	34 ± 1.1 (16-71)
Male	116 (73)	104 (71)
Race
Asian	92 (58)	87 (60)
White	64 (40)	53 (36)
HBV genotype
A	45 (28)	41 (28)
B	28 (18)	28 (19)
C	44 (28)	36 (25)
D	18 (11)	23 (16)
F	12 (8)	5 (3)
Mixed	4 (3)	3 (2)
Indeterminate	7 (4)	8 (5)
Missing	1 (< 1)	2 (1)
Serum HBV DNA, mean ± SE, log10 IU/mL	9.52 ± 0.16	9.66 ± 0.16
Hepatic HBV cccDNA, mean ± SE, log10 copies/HGEq	1.90 ± 0.11	2.0 ± 0.11
Hepatic HBV DNA, mean ± SE, log10 copies/HGEq	0.3 ± 0.05	0.4 ± 0.04
ALT (U/L)
mean ± SE	134.9 (9.84)	132.8 (10.07)
Median (range)	96.0 (23.0-915.0)	90.0 (27.0-715.0)
International normalized ratio	1.1 (0.01)	1.1 (0.01)
Albumin (g/dL)	4.3 (0.04)	4.2 (0.04)
Total bilirubin (mg/dL)	0.8 (0.03)	0.8 (0.03)
Prothrombin time (s)	13.2 (0.16)	13.3 (0.16)
Knodell necroinflammatory score, mean ± SE	7.8 ± 0.23	7.5 ± 0.24
Ishak fibrosis score, mean ± SE	2.4 ± 0.11	2.1 ± 0.11

CccDNA: Covalently closed-circular DNA; ETV: Entecavir; LAM: Lamivudine; HGEq: Human genome equivalent.

Table 2 Virologic and histologic efficacy at week 48 among treated patients with evaluable hepatic hepatitis B virus DNA pairs

Week 48 efficacy (NC = M)	ETV (n = 159)	LAM (n = 146)
Serum HBV DNA, mean ± SE, change from baseline log10 IU/mL	-6.85 ± 0.16	-5.30 ± 0.22
Knodell necroinflammatory score, mean ± SE change from baseline	-3.4 ± 0.26	-3.0 ± 0.29
Ishak fibrosis score, mean ± SE change from baseline	-0.5 ± 0.08	-0.3 ± 0.08

NC = M: Non-completer = missing; ETV: Entecavir; LAM: Lamivudine.

Table 3 Significant associations of baseline factors with baseline hepatic hepatitis B virus covalently closed-circular DNA in univariate linear regression analysis

	Estimate1	95%CI	P value
Baseline serum HBV DNA, per 1 log10 IU/mL	0.11	0.08, 0.13	< 0.0001
Baseline total hepatic HBV DNA, per 1 log10 IU/mL	0.11	0.07, 0.16	< 0.0001
HBV genotype F: Not F	-0.41	-0.67, -0.15	0.0023

¹log₁₀ copies/HGEq. HBV: Hepatitis B virus.

Table 4 Significant associations of baseline and on-treatment factors with hepatic hepatitis B virus cccDNA change from baseline at week 48 in univariate linear regression analysis (adjusted for treatment)

		Estimate1	95%CI	P value
Baseline	Serum HBV DNA, per 1 log10 IU/mL	-0.05	-0.08, -0.01	0.0106
	ALT ≥ 2.6 × ULN : < 2.6 × ULN	-0.42	-0.56, -0.28	< 0.0001
On-treatment	Serum HBV DNA, per 1 log10 IU/mL change from baseline at week 48	0.11	0.08, 0.14	< 0.0001
	Total hepatic HBV DNA, per 1 log10 IU/mL change from baseline at week 48	0.35	0.28, 0.42	< 0.0001
	Knodell necroinflammatory score, per 1 unit change from baseline at week 48	0.04	0.01, 0.06	0.0062
	ALT, per 1 U/L change from baseline at week 48	1.51 × 10-3	0.98 × 10-3, 2.05 × 10-3	< 0.0001
	No HBeAg loss at week 48 : HBeAg loss at week 48	-0.20	-0.38, -0.02	0.0338

¹log₁₀ copies/HGEq. ULN: Upper limit of normal; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen; ALT: Alanine aminotransferase.