阿德福韦治疗慢性乙型肝炎过程中HBV DNA及丙氨酸氨基转移酶水平的变化

目的 研究新药阿德福韦(ADV)治疗慢性乙型肝炎过程中HBV DNA及丙氨酸氨基转移酶(ALT)水平的变化情况,从而指导临床用药. 方法 采集16例慢性乙型肝炎(CHB)患者用ADV治疗前血清,即基线(BL)血清,以及持续服药12、16、28、40、48、52、68、80、92周共10个时段的系列血清.用荧光定量PCR法检测其HBV DNA的水平.用全自动生化仪检测其ALT的水平. 结果 从BL到48周时段,HBV DNA中位数显著下降;在52周,HBV DNA中位数出现反弹;从52至92周时段,HBVDNA中位数再次下降.16例不同时段血清ALIT中位数的变化与HBV DNA中位数变化一致.ADV治疗12周时,HBV DNA中位数较基线下降了2.34 lg拷贝/ml,无HBV DNA阴转、HBeAg血清学转换;治疗28周时,HBV DNA中位数较基线下降了2.91 lg拷贝/ml,有2例HBV DNA阴转、ALT恢复正常、HBeAg血清学转换;治疗40、48周时,HBV DNA中位数较基线分别显著下降了3.83、3.95 kg拷贝/ml,有4例HBV DNA阴转、ALT恢复正常、HBeAg血清学转换;治疗52周时,HBV DNA中位数较基线下降了2.90 lg拷贝/ml,出现反弹,但仍有4例HBV DNA阴转、ALT恢复正常、HBeAg血清学转换;治疗68、80、92周时,HBV DNA中位数较基线显著下降了3.51、3.81、4.01 lg拷贝/ml,分别有4、6、6例HBV DNA阴转、ALT恢复正常、HBeAg血清学转换.16例患者接受ADV治疗的两年中,有9例患者分别从16、28、40周开始HBV DNA的水平显著下降;7例患者HBV DNA的水平下降但不显著. 结论 阿德福韦治疗慢性乙型肝炎过程中,HBV DNA及ALT中位数的变化情况基本一致.52周时段HBV DNA水平出现反弹,提示52周可能是抗病毒的关键时段.

Changes of HBV DNA titers and serum alanine aminotransferase level in chronic hepatitis B patients during adefovir dipivoxil treatment

Objective To study the changes of HBV viral DNA titers and serum alanine aminotransferase(ALT) levels during adefovir dipivoxil(ADV) treatment on chronic hepatitis B (CHB) patient in order to guide the clinical practice. Methods Sixteen CHB patients were treated with ADV for 92 weeks. Blood samples were collected at week 12, 16, 28,40, 52, 68, 80 and 92. ALT and HBV DNA titer were determined by automatic biochemistry analyzer and real-time PCR respectively. Results Mean HBV DNA titers decreased significantly from the start of the treatment to week 48. At week 52, HBV DNA level rebounded instead of decreasing continuously. From week 52 to week 92, HBV DNA decreased again. The change of ALT level was consistent to that of HBV DNA. At week 12, mean reduction of HBV DNA reached to 2.34 lg copies/ml, compared to before trestment baseline (BL), with no patient showing HBV DNA negative and HBeAg seroconversion. At week 28, mean reduction of HBV viral DNA titer was 2.91 lg copies/ml, compared to BL, with two patient showing HBV DNA negative and HBeAg seroconversion. At week 40 and week 48, mean reduction of HBV viral DNA got to 3.83 lg copies/hal and 3. 95 lg copies/ml respectively. Four patients showed HBV DNA negative, ALT normalization and HBeAg seroconversion. At week 52, HBV viral DNA rebounded, with the mean HBV viral DNA reduction climbed to 2.90 lg copies/ml compared to the baseline, even though 4 patients showed HBV DNA negative, ALT normalization and HBeAg seroconversion at this time point. At week 68, 80, 92, mean HBV viral DNA reduction became 3.51,3.81 and 4.01 lg copies/ml, respectively. Additionally, four, six and six patients turned to be HBV DNA negative, ALT recovery and HBeAg seroconversion, respectively. HBV viral DNA titor in 9 patients dropped significantly around week 16-40, but no significant reduction in viral DNA titer was observed in other 7 patients. Conclusions The change of HBV viral DNA load in 16 patients treated with ADV is closely associated with those of their serum ALT levels. Particularly, a significant rebound in viral DNA load was noticed at week 52, a phenomenon not seen in previous reports.