| ObjectiveTo study the efficacy in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with adefovir dipivoxi (ADV) treatment and the relevant factors including serum levels of tumor necrosis factorα(TNF-α),polymorphisms in TNF-αgene promoter region at positions -238 and -308,genotypes and subgenotypes of hepatitis B virus (HBV),and so on.Methods1 203 HBeAg-positive chronic hepatitis B patients from Fujian province were recruited for research and administered with ADV 10 mg once daily for 48 weeks.2 The gene polymorphisms in TNF-αpromoter region at positions -238 and -308 were determined by the restriction fragment length polymorphism (RFLP) assay of polymerase chain reaction (PCR) products, and the serum levels of TNF-αwere examined by enzyme linked immunosorbent assay (ELISA) before and after ADV treatment.3 HBV genotypes were assayed by real-time fluorescent quantitative PCR or sequencing HBV S gene by which HBV subgenotypes could be determined.4 The relationships among the efficacy of ADV treatment,serum levels of TNF-α,polymorphisms in TNF-αpromoter at positions -238 and -308,genotypes and subgenotypes of hepatitis B virus (HBV),and so on were analyzed by logistic regression. Results1 The rate of HBV DNA negativity,alanine aminotransferase (ALT) norma- lization,HBeAg loss and seroconversion,and response in patients at the treatment times of 24 and 48 weeks was 31.5%, 59.1%, 15.8%, 8.9%, 13.3% and 58.6%,78.3%,29.6%,16.7%,25.6% respectively,and meantime the median reduction in serum HBV DNA loads was 3.56 and 4.35log10 copies/ml respectively.Furthermore the therapeutic effects at week 48 were all considerably better than those at week 24 (P<0.05).And there were lower serum levels of TNF-αat week 48 than before treatment in different therapeutic effect groups,which had statistic difference (P<0.001) but the groups of HBV DNA positivity and ALT abnormality.2 The baseline levels of TNF-αin patients with TNF-α-238G/A genotype were significantly lower than those with G/G genotype (P=0.037),but those with -308G/A genotype were significantly higher than those with G/G genotype (P<0.001).3 HBV genotypes in all patients were B and C,58.6% and 41.4% respectively. And in 99 patients by sequencing HBV S gene,there were 52 cases with subgenotype Ba and 47 cases with subgenotype Ce.The average age was younger and the mean body mass index (BMI) was lower in patients with genotype B than genotype C (P=0.020;P<0.001).4 Patients with higher baseline levels of TNF-αhad greater rate of HBeAg loss and response at week 24 and 48 (P=0.028;P=0.040;P=0.038;P=0.014).HBV DNA negativity at week 24 were observed more often in patients with TNF-α-308G/A genotype than G/G (P=0.002).And HBV genotype B achieved greater rate of HBV DNA negativity at week 24 and ALT normalization at week 48 than genotype C (P=0.019;P=0.015). Meanwhile,patients with higher baseline levels of ALT,lower baseline loads of HBV DNA,lower BMI,female or younger age had better correspon- ding therapeutic effect,and some therapeutic effects at week 24 influenced on some at week 48.5 The baseline levels of TNF-α,polymorphisms in TNF-αpromoter at positions -238 and -308 were not significantly associated with HBV genotype B and C (P>0.05).Meanwhile,the baseline levels of TNF-αwas showed negative trend with the baseline loads of HBV DNA (r=- 0.151,P=0.031),while positive trend with the baseline levels of ALT (r=0.333,P<0.001).The baseline loads of HBV DNA in patients with TNF-α-308G/A genotype was significantly lower than those with G/G genotype (P=0.019).Conclusions1 ADV can be effective to inhibit the copy of HBV and ameliorate liver inflammation during treatment for patients with HBeAg-positive chronic hepatitis B.Also the therapeutic effects at week 48 are better than those at week 24.2 Higher baseline levels of TNF-αmay be observed more often in patients with TNF-α-238G/G or -308G/A genotype,and may predict higher probability for winning HBeAg loss and response at week 24 and 48.Also TNF-α-308G/A genotype may be a helpful factor for achieving greater rate of HBV DNA negativity at week 24.3 The major popular genotypes of HBV are B and then C,but only subgenotype Ba and Ce are found in our research.Patients with genotype B may be younger,have lower BMI and be more prone to HBV DNA negativity at week 24 and ALT normalization at week 48 than those with genotype C.4 The baseline levels of ALT,baseline loads of HBV DNA,gender,age or BMI may influence on corresponding therapeutic effect.Also some therapeutic effects at week 24 may predict some at week 48.5 The baseline levels of TNF-α,polymorphisms in TNF-αpromoter at positions -238 and -308 may be not associated with HBV genotype B and C.
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