Viral blips during long-term treatment with standard or double dose lamivudine in HBe antigen negative chronic hepatitis B

Table 1 Baseline characteristics of the patients

	Lam-200	Lam-100	P
Number of patients	12	35	NS
Age (median; range)	44.5 (32-60)	44 (23-72)	NS
BMI median (range)	24.3 (23.2-28.7)	25.5 (20.9-34.3)	NS
Gender (M/F)	11/1	26/9	NS
Histology			NS
Minimal-Mild	1 (14%)	6 (22%)
Moderate-Severe	3 (43%)	7 (26%)
Cirrhosis	3 (43%)	14 (52%)
ALT (x n.v.)			NS
< 3	4 (33.3%)	16 (50%)
3-5	3 (25%)	5 (15.6%)
> 5	5 (41.7%)	11 (34.4%)
HBV-DNA IU/mL median (range)	1.06 × 106 (3.2 × 104-3.8 × 106)	6 × 105 (2.4 × 104-3.5 × 106)	NS
Months of therapy median (range)	28 (8-50)	28 (9-48)	NS

Table 2 Virological responses in the two treatment groups n (%)

	Lam-100 (n = 35)	Lam-200 (n = 12)
Primary responses	29 (82)	12 (100)
Breakthroughs	7 (24.6)	2 (16.6)
End of study responses (amplicor)	22 (62.8)	10 (83.3)
Stably undetectable HBV-DNA by RT-PCR	18 (51.4)a	10 (83.3)a

^aP = 0.051; 51.4% vs 83.3%.

Table 3 Viral blips observed during treatment. A viral blip is a transiently detectable viremia below 4 × 10² copies/mL in a responder patient

	Lam 100	Lam 200	Total
Primary responders (n)	29	12	41
Viral blips n (%)	10 (34.4)	1 (8.3)	11
Breakthroughs no.	7	2	9
Viral blips n (%)	6 (85.7)	1 (50)	7 (77.7)a
End of study responses (Amplicor)	22	10	32
Viral blips n (%)	4 (18.2)	0	4 (12.5)a

^aViral blips among patients with breakthroughs vs viral blips among patients with end of study response; 77.7% vs 12.5%; P = 0.001.

Table 4 Lamivudine resistance mutations and HBV genotypes in patients with a virological breakthrough or primary non-response

Patients	Genotype	Baseline	Mutation (mo)
Breakthrough
11	D	Wt	rtM204V (11)
12	D	Wt	None (19)
23	D	Wt	rtM204V (24)
14	A	Wt	rtM204V
			rtL180M (28)
15	D	Wt	rtM204V
			rtL180M (32)
16	D	Wt	rtM204V
			rtL180M (19)
17	D	Wt	rtM204V
			rtL180M (21)
18	D	Wt	rtM204I (12)
Primary non-response
11	D	Wt	rtM204I (9)
12	D	Wt	rtM204V (11)
13	D	Wt	rtM204I (11)
14	D	Wt	rtM204I (9)
15	D	Wt	rtM204I (12)

Treatment group:

¹LAM:100;

²LAM:200.