Baseline HBV DNA level is the most important factor associated with virologic breakthrough in chronic hepatitis B treated with lamivudine

Table 1 Baseline characteristics of patients (mean ± SD)

	All patients(n = 79)	Breakthrough(n = 24)	Non-breakthrough(n = 55)
Age (yr)	47 ± 12	47 ± 13	47 ± 11
Female (%)	32	29	33
Family history of CHB (%)	47	46	55
ALT (IU/L)	149 ± 44	98 ± 20	171 ± 63
Total bilirubin (mg/dL)	1.1 ± 1.1	1.3 ± 1.4	1.0 ± 0.9
Albumin (g/dL)	4.4 ± 0.4	4.2 ± 0.5	4.3 ± 0.4
(INR)	1.07 ± 0.12	1.09 ± 0.15	1.06 ± 0.08
Cirrhosis (%)	30	36	24
HBeAg-positive (%)	43	56	36
HBV DNA log10 copies/mLa	6.0 ± 1.6	6.6 ± 1.5	5.7 ± 1.5
Mean duration of lamivudine treatment (mo)	26 ± 10	29 ± 11	25 ± 10
3 log < HBV DNA < 5 log (%)	19	3	16
HBV DNA ≥ 5 log (%)	60	21	39

^aP < 0.05 breakthrough vs non-breakthrough group INR: International normalized ratio..

Table 2 Response to lamivudine before breakthrough (mean ± SD)

	HBeAg-positive hepatitis (n = 34)			HbeAg-negative hepatitis (n = 45)
	All patients(n = 34)	BT(n = 14)	No BT(n = 20)	All patients(n = 45)	BT(n = 10)	No BT(n = 35)
Max suppression (log10 copies/mL)	4.7 ± 1.4	4.8 ± 1.7	4.6 ± 1.2	4.3 ± 1.6	4.3 ± 1.7	4.3 ± 1.6
Initial suppression (log10 copies/mL)	4.2 ± 1.7	4.2 ± 2.0	4.3 ± 1.5	3.3 ± 2.1	2.8 ± 2.5	3.4 ± 1.9
Patients with IVR (%)	80	75	83	81	67	85
Patients at 6 mo biochemical response (%)	90	82	94	84	86	83
Patients at 12 mo biochemical response (%)	96	100	93	82	80	82
Time to first detection of BT	-	26 ± 10	-	-	32 ± 12	-

BT: Breakthrough; Max suppression: Maximal virologic suppression; Initial suppression: Initial virologic suppression; IVR: Initial virologic response at 6 mo; Biochemical response: ALT normalization.

Table 3 HBV genotypes, variants, and lamivudine-resistant mutants

Patients with VBT				During BT
Patient	Sex	BT	Genotype	Month after LAM	ALT	HBeAg	HBV DNA log10 copies/mL	PC	CP A1763T G1765A	L180M	M204I/V
1	F	+	C	19	90	-	5.4	Wild	TA	M	I/V
2	M	+	C	18	29	-	3	Stop	TA	L	I/V
3	F	+	C	12	12	+	6.8	Wild	AG	L	M
4	M	+	C	18	44	+	8.3	Wild	TA	M	I/V
5	M	+	C	36	NA	+	5.2	Wild	TA	M	I/V
6	F	+	C	21	42	+	5.7	Wild	AG	L	M
7	M	+	C	27	24	+	6.6	Stop	TA	M	I/V
8	F	+	C	21	NA	+	6.7	Wild	AG	L	M
9	F	+	C	30	108	+	6.7	Wild	TA	M	I/V
Patients without VBT				End of follow-up
Patient	Sex	BT	Genotype	Month after LAM	ALT	HBeAg	HBV DNA log10 copies/mL	PC	CP A1763T G1765A	L180M	M204I/V
1	M	-	C	9	28	+	4.6	Wild	TA	L	M
2	M	-	C	30	NA	+	5.4	Wild	TA	L	M
3	M	-	C	32	12	-	1	UD	UD	L	M
4	M	-	C	27	NA	+	1	Wild	TA	L	M
5	M	-	C	36	42	-	1	UD	UD	L	M
6	M	-	C	24	24	+	1	Wild	TA	UD	UD

PC: Precore mutants; CP: Core promotor mutants; SR: Suboptimal response; NA: Not available; UD: Undetectable; LAM: Lamivudine; BT: Breakthrough; VBT: Virologic breakthrough.