Resistant mutants induced by adefovir dipivoxil in hepatitis B virus isolates

Table 1 Loci distribution of adefovir dipivoxil -resistant mutants n (%)

ADV-resistant mutants	Number of patients	prevalence of patients
rtA181T12 mutant/coexisting mutants3	40 (50.63)
rtV214A1 mutant/coexisting mutants	7 (8.86)
rtN236T1 mutant/coexisting mutants	5 (6.33)
rtP237H1 mutant	1 (1.27)
rtL180M4 + rtM204V456 + rtA181T12 coexisting mutants	4 (5.06)
rtL180M4 + rtT184L6 coexisting mutants, rtM204V45 + rtV207M/L/I4 + rtV214A1 mutant	1 (1.27)
rtL180M4 + rtM204V456 + rtS213T4 + rtA181T12 mutant	1 (1.27)
rtL180M4 + rtM204V456 + rtS213T4 + rtQ215S1 mutant, rtP237H1 coexisting mutants	1 (1.27)
rtL180M4 + rtM204V456 + rtQ215S1 + rtT184L6 mutant	1 (1.27)
rtL180M4 mutant, rtQ215S1 coexisting mutants	1 (1.27)
rtA181T12 + rtV214A1 coexisting mutants	1 (1.27)
rtA181T12 + rtN236T1 coexisting mutants	2 (2.53)
rtA181T1 mutant, rtN236T1 coexisting mutants	1 (1.27)
rtM204V45 + rtA181T12 coexisting mutants	1 (1.27)
rtM204V45 mutant, rtA181T12 coexisting mutants	1 (1.27)
rtM204V45 + rtV207M/L/I4 + rtQ215S1 mutant	1 (1.27)
rtM204V45 + rtV214A1 mutant	1 (1.27)
rtM204V45 mutant, rtA181T12 + rtQ215S1 coexisting mutants	1 (1.27)
rtM204V45 mutant, rtN238T1 coexisting mutants	1 (1.27)
rtV207M/L/I4 + rtA181T12 + rtV214A1 + rtN236T1 + rtM250L6 coexisting mutants	1 (1.27)
rtV207M/L/I4 + rtA181T12 + rtN236T1 coexisting mutants	1 (1.27)
rtV207M/L/I4 + rtV214A1 coexisting mutants	1 (1.27)
rtV207M/L/I4 + rtA181T12 + rtN236T1 coexisting mutants	1 (1.27)
rtS213T4 + rtA181T12 coexisting mutants	1 (1.27)
rtS213T4 + rtN236T1 + rtM250L6 mutant	1 (1.27)
rtN236T1 + rtN238T1 coexisting mutants	1 (1.27)

¹ADV-associated mutants: rtA181T, rtV214A, rtQ215S, rtN236T, rtP237H, rtN238T;

²Shared mutants of ADV, LAM, LdT: rtA181T[2];

³Coexisting mutants: wild strain and mutant strain coexistence;

⁴Lamivudine (LAM)-associated mutants: rtL180M, rtM204V, rtV207M/L/I, rtS213T;

⁵Telbivudine (LdT)-associated mutant: rtM204V;

⁶Entecavir (ETV)-associated mutants: rtT184L, rtM204V, rtM250L. ADV: Adefovir dipivoxil.

Table 2 Clinical features of rtA181T mutant and non-mutant rtA181T groups n (%)

Clinical features	rtA181T(n = 56)	Not rtA181T(n = 23)	Statistical value	P-value
Gender (M/F)	48/8	18/5	χ2 = 0.659	0.507
Age (yr, mean ± SD)	43.1 ± 9.3	43.4 ± 11.6	t = 0.132	0.896
End-stage liver disease1	21 (37.5)	11 (47.83)	χ2 = 0.721	0.396
NAFLD	21 (37.5)	9 (39.13)	χ2 = 0.018	0.892
E-antigen (+/–)	27/29	18/5a	χ2 = 6.004	0.023
Genotype (B/C)	7/49	9/14b	χ2 = 7.159	0.007
HBV DNA (log10 copy/mL)	5.16 ± 1.23	5.14 ± 1.25	t = 0.086	0.932
Duration of treatment (mo, mean ± SD)	41.2 ± 10.1	40.8 ± 9.7	t = 0.162	0.872

¹End-stage liver disease: included hepatitis cirrhosis, liver failure, and primary hepatocellular carcinoma.

^aP < 0.05, status of e-antigen in the rtA181T mutant group vs in the not-rtA181T mutant group;

^bP < 0.01, genotype (B/C) in the rtA181T mutant group vs the not-rtA181T mutant group. NAFLD: Non-alcoholic fatty liver disease; HBV: Hepatitis B virus.

Table 3 Clinical features of single mutant and multi-mutant groups n (%)

Clinical features	Single mutant(n = 53)	Multi-mutants(n = 26)	Statistical value	P-value
Gender (M/F)	45/8	21/5	χ2 = 0.217	0.749
Age (yr, mean ± SD)	42.6 ± 10.5	44.5 ± 8.9	t = 0.806	0.423
End-stage liver disease1	21 (39.62)	11 (42.31)	χ2 = 0.721	0.396
NAFLD	19 (35.85)	11 (42.31)	χ2 = 0.137	0.712
E-antigen (+/–)	24/29	12/14	χ2 = 0.005	1.000
Genotype (B/C)	10/43	6/20	χ2 = 0.022	0.883
HBV-DNA (log10 copy/mL)	5.06 ± 1.24	5.35 ± 1.21	t = 0.989	0.326
Duration of treatment (mo, mean ± SD)	38.6 ± 8.2	43.9 ± 10.8a	t = 2.426	0.018

¹End-stage liver disease: included hepatitis cirrhosis, liver failure, and primary hepatocellular carcinoma.

^aP < 0.05 duration of treatment in the single mutant group vs the multi-mutants group. NAFLD: Non-alcoholic fatty liver disease; HBV: Hepatitis B virus.

Table 4 Clinical features of the rtA181T mutant and rN236T groups n (%)

Clinical features	rtA181T mutant(n = 50)	rtN236T mutant(n = 7)	Statistical value	P-value
Gender (M/F)	43/7	7/0	χ2 = 0.069	0.792
Age (yr, mean ± SD)	42.6 ± 9.4	47.3 ± 12.1	t = 1.201	0.235
End-stage liver disease1	19 (38)	3 (42.86)	χ2 = 0.026	1.000
NAFLD	20 (40)	3 (42.86)	χ2 = 0.009	1.000
E-antigen (+/–)	25/25	2/5	χ2 = 1.131	0.427
Genotype (B/C)	7/43	5/2a	χ2 = 5.958	0.028
HBV-DNA (log10 copy/mL)	5.18 ± 1.23	4.91 ± 1.20	t = 0.544	0.588

¹End-stage liver disease: included hepatitis cirrhosis, liver failure, and primary hepatocellular carcinoma.

^aP < 0.05 genotype (B/C) in the rtA181T mutant group vs the rtN236T mutant group. NAFLD: Non-alcoholic fatty liver disease; HBV: Hepatitis B virus.