联合阿德福韦酯或换用恩替卡韦治疗拉米夫定耐药慢性乙型肝炎患者的临床观察

目的观察拉米夫定(LAM)耐药的慢性乙型肝炎(CHB)患者,加用阿德福韦酯(ADV)联合治疗与换用恩替卡韦(ETV)挽救治疗的疗效。方法将拉米夫定治疗失败的CHB患者52例分为两组,31例接受ADV(10mg/d)联合LAM(100mg/d)治疗(ADV联合组),21例给予ETV(1mg/d)治疗(ETV组),治疗至72周,观察24、48、72周时丙氨酸转氨酶(ALT)复常率、HBV DNA载量、血清学标志及病毒学突破情况。结果①ADV联合组和ETV组治疗24周时的生化学应答率分别为61.3%和57.1%,治疗48周时分别为74.2%和66.7%,治疗72周时分别为80.6%和76.2%。两组患者的生化学应答率无统计学差异(P>0.05)。②治疗72周时两组HBV DNA阴转率分别是71.0%和42.9%,差异具有统计学意义(P<0.05).在治疗24周、48周时,ADV联合组和ETV组的血清HBV DNA较基线下降的平均水平相似(分别为-2.0、-2.1,-2.4、-2.3log10copies/mL),治疗72周时,ADV联合组的HBV DNA下降更加明显(-4.4、-2.4log10copies/mL,P<0.05)。治疗72周时两组分别有2例和3例患者发生病毒学突破。③治疗72周时两组有5例HBeAg阴转,其中2例HBeAg血清转换,3例HBeAb阴性。两组的血清学转换率均较低。结论在拉米夫定耐药CHB患者中,ADV联合组和ETV组治疗72周,两组生化学应答及24、48周的抗病毒效果相似,但随着治疗时间延长至72周,ADV联合组病毒学应答率显著高于ETV组,且ADV联合组治疗的患者病毒学突破发生率更低。

Efficacy of Adefovir Add-on Lamivudine Combination Therapy Compared with Switching to Entecavir Monotherapy in LAMresistant Patients with Chronic Hepatitis B

Objective To study the comparative effect of adefovir(ADV) add-on lamivudine(LAM) versus switching to entecavi r(ETV) in LAM-resistant patients with chronic hepatitis B.Methods Fifty-two LAM-resistant patients with chronic hepatitis B were included in the following two treatment groups;group 1(n=31),ADV was added to LAM(10 mg once a day),and group 2(n=21),LAM was switched to ETV(1.0 mg once a day).All patients were followed for at least 72 weeks.The parameters including normalization of serum alanine aminotransferase(ALT) levels,virologic response,virologic breakthrough,and HBeAg seroconversion rates were studied at 24,48 and 72 weeks.Result ①In the LAM+ADV and ETV groups,the rates of ALT normalization were 61.3 % and 57.1% at weeks 24;74.2% and 66.7% at weeks 48;80.6% and 76.2% at weeks 72,respectively,and significant differences in ALT normalization rates were not detected.②The rates of undetectable HBV DNA were 71.0% and 42.9 %,respectively.The mean reduction in serum HBV DNA at 24 and 48 weeks post treatment was similar between the ADV combination and ETV therapy groups(-2.0 vs.-2.1 and-2.4 vs.-2.3 log10 copies/mL).However,72 weeks post treatment,theADV combination group had a significant reduction in HBV DNAlevels compared to the ETV treatment group -4.4 vs.-2.4(P< 0.05) log10 copies/mL],and virologic breakthrough in 2 and 3 respectively.③HBeAg seroconversion was 2 and 3 cases in the ADV add-on LAM group and ETV group,respectively,72 weeks post treatment.The rate of HBeAg seroconversion was both lower between the two groups.Conclusions In LAM-resistant patients with chronic hepatitis B,the rates of ALT normalization and reduction of HBV DNA at 24 and 48 weeks post treatment was similar between the ETV and ADV combination therapy groups.However,the rate of viral respone was significially higher in the ADV add-on LAM group.Compared with switching to ETV monotherapy,ADV add-on LAM therapy was more effective at reducing the viral load in patients with LAM resistance,and virologic breakthrough was lower in the ADV add-on LAM therapy.