Virological response to adefovir monotherapy and the risk of adefovir resistance

Table 1 Baseline characteristics of patients

Variables
No. of patients	77
Age (yr, mean ± SD)	49.3 ± 11.7
Female: Male (n, % male)	18: 59 (77%)
HBeAg positive (n, % positive)	21: 56 (73%)
ALT (U/L, median, range)	119 (25–926)
AST (U/L, median, range)	77 (30–483)
Albumin (g/dL, median, range)	4.0 (2.6–4.6)
Total bilirubin (mg/dL, median, range)	1.0 (0.3–4.0)
Prothrombin time (INR, median, range)	1.1 (0.9–1.7)
Baseline creatinine level (mg/dL, mean ± SD)	0.90 ± 0.13
Creatinine level at weeks 96 (mg/dL, mean ± SD)	0.94 ± 0.16
LAM resistance mutation profile (n, %)
rtM204I ± rtL180M	48 (62%)
rtM204V ± rtL180M	29 (38%)

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; INR: International normalized ratio; LAM: Lamivudine.

Table 2 Patterns of ADV-resistant mutations at weeks 48 and 96 after ADV monotherapy in LAM-resistant patients

Variables	Week 48	Week 96
rtA181T	5	5
rtA181V	2	5
rtA181V + rtN236T	1	2
rtA181T + rtN236T	0	2
Total n (%)	8 (10)	14 (18)

LAM: Lamivudine; ADV: Adefovir dipivoxil; rtA181V/T and/or rtN236T: ADV-resistant strain.

Table 3 HBV DNA levels during ADV monotherapy according to emergence of ADV-resistant mutations in LAM-resistant patients

HBV DNA level	ADV resistanceat week 96 (n = 14)	No ADV resistanceat week 96 (n = 63)	P value
Baseline (log10 IU/mL, mean ± SD)	7.1 ± 0.7	6.8 ± 1.0	0.245
Month 3 (log10 IU/mL, mean ± SD)	4.2 ± 1.6	3.1 ± 1.6	0.027
Month 6 (log10 IU/mL, mean ± SD)	4.1 ± 1.4	2.7 ± 1.6	0.002
Month 12 (log10 IU/mL, mean ± SD)	3.9 ± 1.3	2.4 ± 1.5	0.002

LAM: Lamivudine; ADV: Adefovir dipivoxil; HBV: Hepatitis B virus.

Table 4 Incidence of ADV resistance according to HBV DNA levels

HBV DNA level	Patient number	ADV resistance at week 48 n (%)	ADV resistance at week 96 n (%)
Week 12a
< 60 IU/mL	18	2 (11)	2 (11)
≥ 60 to < 2000 IU/mL	21	0 (0)	0 (0)
> 2000 IU/mL	38	6 (16)	12 (32)
Week 24b
< 60 IU/mL	26	2 (8)	2 (8)
≥ 60 to < 2000 IU/mL	19	1 (5)	1 (5)
> 2000 IU/mL	32	5 (16)	11 (34)
Week 48c
< 60 IU/mL	34	2 (6)	2 (6)
≥ 60 to < 2000 IU/mL	16	0 (0)	3 (19)
> 2000 IU/mL	27	6 (22)	9 (33)

^aP value; week 48 = 0.162, week 96 = 0.007.

^bP value; week 48 = 0.431, week 96 = 0.008.

^cP value; week 48 = 0.036, week 96 = 0.022. ADV: Adefovir dipivoxil; HBV: Hepatitis B virus.

Table 5 Virological response in predicting ADV resistance at week 96

Variables	Adefovir resistance	Sensitivity (%, 95% CI)	Specificity	Positive predictive value	Negative predictive value
	n (%)		(%, 95% CI)	(%, 95% CI)	(%, 95% CI)
HBV DNA level ≥ 60 IU/mL at Week 12 (n = 59)	12 (20)	85 (56–97)	25 (15–38)	20 (11–33)	89 (63-98)
HBV DNA level > 2000 IU/mL at Week 12 (n = 38)	12 (32)	85 (56–97)	58 (45–70)	31 (18–48)	84 (81–99)
HBV DNA level ≥ 60 IU/mL at Week 24 (n = 51)	12 (24)	85 (56–97)	38 (26-51)	23 (13–38)	92 (73–98)
HBV DNA level > 2000 IU/mL at Week 24 (n = 32)	11 (34)	78 (48–94)	66 (53–77)	34 (19–53)	93 (80–98)
HBV DNA level ≥ 60 IU/mL at Week 48 (n = 43)	12 (28)	85 (56–97)	51 (38–63)	28 (16–44)	72 (56–84)
HBV DNA level > 2000 IU/mL at Week 48 (n = 27)	9 (33)	64 (35–86)	71 (58–81)	33 (17–53)	90 (77–96)

ADV: Adefovir dipivoxil; HBV: Hepatitis B virus.