Analysis Of Factors Accociated With Entecavir Anti-HBV Efficacy

objective:To observe the clinical efficacy of ETV anti-HBV and establish predictors of its efficacy. To analyze the distribution, clinical characteristics of different HBV genotypes in the experiments and the relationship with HBV genotypes and hepatitis disease spectrum and explore the relationship between HBV genotypes and efficacy of ETV.Method:1. Retrospective comparative analysis of clinical efficacy of ETV on 75 CHB patients with HBeAg-positive, compensated liver function in 48 weeks (baseline ALT in the 1.2-10×ULN, HBV DNA≥5 log10copies/ml).Analyse the relationship between the baseline level and anti-HBV efficacy of ETV in accordance with the baseline ALT and HBV DNA load.2. Comparative analyse the response of 64 CHB patients with HBeAg-positive and 15 CHB patients with HBeAg-negative to ETV in 24 weeks and 48 weeks according to the level of serum HBV DNA load for 4 weeks.3.22 patients infected with HBV were detected HBV genotype, then observed the distribution, clinical characteristics of different HBV genotypes in the experiments and explored the relationship between HBV genotypes and efficacy of ETV.Results:1. In the 75 HBeAg-positive CHB patients with compensated liver function (baseline ALT in the 1.2-10×ULN, HBV DNA≥5 log10copies/ml) by administration of ETV for 48 weeks, ALT normalization rate was 81.3%, HBV DNA negative conversion rate was 70.7%, HBeAg negative conversion rate was 30.7%, HBeAg seroconversion rate was 24%, response rate was 96.0%, non-response rate was 4.0%.①In the experimemt there were three groups according to the baseline levels of ALT:＜2×ULN group of 32 cases,2～5×ULN group of 34 cases,5～10×ULN group of 9 cases. ALT normalization rate were 76.5%,85.3% and 91.2% in the ALT 2～5×ULN group in 12,24,48 weeks, which was significantly higher than ALT＜2×ULN group 46.9%,59.4% and 68.8% (P＜0.05); HBV DNA negative conversion rate in 24,48 week was 70.6% and 88.9% in 2～5×ULN group, which was significantly higher than ALT＜2×ULN group 43.8% and 56.3%) (P＜0.05); HBV DNA negative conversion rate was 79.4% in ALT 5～10×ULN group in 24 week, which was significantly higher than ALT＜2×ULN group 59.3%(P＜0.05); HBeAg negative conversion rates were 35.3%,44.4% respectively in 48 weeks in ALT 2～5×ULN group and 5～10×ULN group, Which were significantly higher than＜2×ULN group12.5%(P＜0.05); There were no significant difference among the three groups in 48 weeks for HBeAg serology conversion and response rate; Serum ALT and HBV DNA load declined most rapidly in ETV treatment the first 4 weeks in the three groups.2. In the experimemt there were two groups according to the baseline levels of HBV DNA load:5～7 log10copies/mL group of 38 cases and＞7 log10copies/mL group of 37 cases. ALT normalization rate were 76.7%,89.5% and 94.7% in 12,24,48 weeks in HBVDNA 5～71og10copies/mL group, which was significantly higher than HBVDNA＞7 log10copies/mL group 51.4%,59.5% and 67.6% (P＜0.05); HBV DNA negative conversion rate was 63.2%,76.3% and 89.5% in 12,24,48 weeks in 5～7 log10copies/mL group, which was significantly higher thanHBVDNA＞7log10copies/mL group 35.1%,45.9% and 51.4%(P＜0.05); There were no significant difference between the two groups fpr the HBeAg negative conversion rate, HBeAg seroconversion rates and complete response rate in 48 weeks:3. The fastest stage of serum ALT, HBV DNA decline is ETV s treatment for first 4 weeks.The patients of Pre-treatment serum ALT≥2×ULN whose serum ALT, HBV DNA decline was steeper in first 4 weeks.4. CHB patients were treated with ETV, then analyse the relationship of the level of serum HBV DNA load in 4 weeks the response in 24,48 weeks, the results showed:①In the 64 case of HBeAg-positive CHB patients, there were HBV DNA≤3 log10copies/mL group (9 cases), HBV DNA3～5 log10copies/mL group (21 cases) and HBV DNA>51og10copies/mL group (34 cases) according to the 4 week HBV DNA load. Virologic response of the three group were nearly 100% in 24,48 weeks, but there were no significant difference among them; biochemical response rate were 100% and 84.2% o in HBV DNA load≤3 log10copies/mL group and 3～5 log10copies/mL group of 4 weeks, they were significantly higher than HBV DNA＞5 log10copies/mL group of 4 weeks(23.8%) (P＜0.05); Biochemical response rate were both 100% in HBV DNA load≤3 log10copies/mL group and 3～5 log10copies/mL group, which were significantly higher than HBV DNA＞51og10copies/mL group (42.9%) of 4 weeks in 48 weeks; the serological response rates were 45.8%,36.8% and 9.6% above the three groups in 48 weeks which serological response rates were 45.8%,31.6% and 0% in 24 weeks, there were no significant fifference among the three groups;②According to HBVDNA load in 4 weeks, there were HBV DNA load≤3 log10copies/mL group (7 cases),3～5 log10copies/mL group (5 cases) and＞5log10copies/mL group (3 cases) in the 15 case of HBeAg-negative CHB patients; The virologic response rates of the patients who HBV DNA load≤3 log10copies/mL group and 3～5 log10copies/mL group at the 4 weeks were both 100% and significant higher than 33.3% virologic response rate at the 24 weeks of the patients who HBV DNA＞5log10copies/mL in 4 week, (P＜0.05), But at 48 weeks, this difference were no significant; the biochemical response rates of the three groups were no significant difference.5. HBV Genotype of 22 patients were detected, of which B genotype were 6 cases, C genotype were 14 cases and two patients had no sub-type. In the study, there was no significant difference on the genotypes distribution, clinical characteristics and the relation between the B and C genotypes and clinical disease spectrum of the patients infecting B, C genotypes virus.HBV genotype has nothing to do in the clinical efficacy of ETV against HBV.Conclusion:1. There were better clinical efficacy and safety on ETV againsting HBV.2. Baseline ALT, HBV DNA load levels could be used as ETV anti-HBV preditors factors of efficacy in the 12,24,48-week for HBeAg-positive patients with compensated liver function3. Serum HBV DNA load in the 4 weeks could be used as efficacy predictors in the 24, 48 weeks for HBeAg-positive or-negative CHB patients with ETV treatment.4. In the study, there were no significant difference on the clinical charactertis and ETV anti-HBV efficacy of B,C genotype.