Effects of antiviral agents and HBV genotypes on intrahepatic covalently closed circular DNA in HBeAg-positive chronic hepatitis B patients

Table 1 Demographic, histological, biochemical, virological data obtained from three antiviral therapies (mean ± SD)

Parameter	Sequential lamivudine -INF-αtherapy	Lamivudine monotherapy	Interferon monotherapy
Number of patients	24	35	12
Sex ratio (male/female)	21/3	29/6	9/3
Mean age (y)	33 ± 6	32 ± 5	31 ± 8
Mean Knodell score
pretreatment	8.9 ± 3.6	8.2 ± 4.5	7.1 ± 4.0
post-treatment	6.6 ± 4.0a	5.6 ± 3.2a	5.0 ± 2.8
Mean ALT level (nkat/L)
Pretreatment	3423 ± 2388	4390 ± 2454	3006 ± 1720
Post-treatment	668 ± 400a	667 ± 384a	1686 ± 1286a
Serum HBV DNA (log10)
Pretreatment	7.5 ± 1.3	7.7 ± 0.8	7.8 ± 1.1
Post-treatment	3.8 ± 1.0a	3.7 ± 1.2a	5.0 ± 1.5ac
Intrahepatic HBV DNA (log10)
Pretreatment	5.8 ± 1.2	6.2 ± 0.9	6.3 ± 0.9
Post-treatment	4.7 ± 1.1a	4.6 ± 1.5a	5.6 ± 1.5ac
Intrahepatic ccc DNA (log10)
Pretreatment	5.1 ± 1.0	5.2 ± 1.2	5.8 ± 1.2
Post-treatment	3.4 ± 1.3a	3.8 ± 1.1a	5.0 ± 1.5c
HBeAg seroconversion
rate at the treatment completion	8/21 (38.1%)	6/32 (18.6%)	3/12 (25%)
Sustained virological response
rate at 24 wk off treatment	4/16 (25%)	13/31 (41.9%)	1/1 (100%)

^aP < 0.05 vs post-treatment,

^cP < 0.001 vs sequential lamivudine - INF-α therapy and lamivudine monotherapy. HBeAg seroconversion rate at the end of treatment: some post-treatment data were lost, ALT: Alanine aminotransferase, ccc DNA: Covalently closed circular DNA.

Table 2 Histological, biochemical and virological data on different therapy responses (mean ± SD)

Parameter	HBeAg positive	HbeAg serocon -version	Sustained virological response	Virological flares
Number of patients	48	17	18	30
Mean Knodell score
Pretreatment	8.4 ± 4.1	7.1 ± 4.2	8.0 ± 4.0	8.4 ± 3.9
Post-treatment	6.0 ± 3.6	5.1 ± 3.1a	6.1 ± 3.0	5.2 ± 2.7a
Mean ALT level (nkat/L)
Pretreatment	3206 ± 2338	3841 ± 2371	3340 ± 2638	4576 ± 2505
Post-treatment	1018 ± 985	618 ± 384a	517 ± 300	601 ± 400
24 wk off- treatment			851 ± 200	380 ± 183e
Serum HBV DNA (log10)
Pretreatment	7.9 ± 0.9	7.5 ± 1.0	7.3 ± 1.3	7.6 ± 0.8
Post-treatment	4.4 ± 1.4a	3.0 ± 0.2ac	3.1 ± 0.3a	3.3 ± 0.4a
24 wk off-treatment			3.2 ± 0.3	6.1 ± 0.8ac
Intrahepatic HBV DNA (log10)
Pretreatment	6.3 ± 0.8	5.6 ± 1.2	5.9 ± 0.8	6.0 ± 1.1
Post-treatment	5.1 ± 1.5	4.1 ± 0.8a	4.5 ± 1.6	4.3 ± 1.0a
Intrahepatic ccc DNA (log10)
Pretreatment	5.5 ± 1.1	5.8 ± 1.0	4.6 ± 1.0	5.4 ± 0.8e
Post-treatment	3.9 ± 1.5	2.8 ± 1.3ac	4.0 ± 0.9	3.8 ± 0.8a

^aP < 0.05 vs post-treatment,

^cP < 0.05 vs HBeAg positive,

^eP < 0.05 vs sustained virological response. ALT: Alanine aminotransferase; ccc DNA: Covalently closed circular DNA.

Table 3 Histological, biochemical and virological data on HBV genotypes C and B (mean ± SD)

Parameter	HBV Genotype C	HBV Genotype B
Number of patients	61	10
Sex ratio (male/female)	50/11	9/1
Number of Sequential therapy	20 (32.8%)	4 (40%)
Number of Lamivudine therapy	31 (50.8%)	4 (40%)
Number of Interferon therapy	10 (16.4%)	2 (20%)
Mean Knodell score
Pretreatment	8.1 ± 4.1	5.7 ± 3.2
Post-treatment	6.0 ± 3.4a	5.4 ± 3.1
Mean ALT level (nkat/L)
Pretreatment	3390 ± 2438	2438 ± 2296
Post-treatment	901 ± 918	551 ± 233
24 wk off-treatment	1503 ± 1336	1987 ± 1720
Serum HBV DNA (log10)
Pretreatment	7.7 ± 1.2	7.6 ± 0.8
Post-treatment	4.05 ± 1.3a	4.9 ± 1.2a
24 wk off-treatment	5.1 ± 1.6	5.3 ± 1.3
Intrahepatic HBV DNA (log10)
Pretreatment	6.1 ± 0.9	5.6 ± 1.5
Post-treatment	4.9 ± 1.4a	4.7 ± 1.2a
Intrahepatic ccc DNA (log10)
Pretreatment	5.6 ± 1.1	5.8 ± 0.5
Post-treatment	3.5 ± 1.2a	3.9 ± 1.9
Sustained virological response rate at
24 wk off-treatment	29.4% (15/51)	30% (3/10)
ALT normalization rate at
24 wk off-treatment	39.3% (24/51)	30% (3/10)

^aP < 0.05 vs post-treatment. ALT: Alanine aminotransferase; ccc DNA: Covalently closed circular DNA.