替诺福韦酯治疗34例慢性乙型肝炎核苷(酸)类似物经治患者的临床分析

目的观察替诺福韦酯(TDF)对慢性乙型肝炎(CHB)核苷(酸)类似物经治患者的临床疗效。方法回顾性分析TDF治疗34例CHB核苷(酸)类似物经治患者48周的临床资料,其中原发治疗失败患者18例、抗病毒耐药患者16例。分析第12、24、48周时HBV DNA阴转率、ALT复常率和48周的HBeAg血清转换率以及不良事件发生率。两组间比较采用t检验,多组间比较采用单因素方差分析。结果第12、24、48周的HBV DNA阴转率分别为35.3%、67.6%和94.1%。治疗前及治疗第12、24、48周的ALT分别为(63.9±18.9)、(49.8±11.9)、(42.7±7.3)和(35.1±3.9)U/L,治疗前后比较,差异有统计学意义(F=36.3,P0.05),48周时ALT复常率为91.1%。第48周时HBeAg阴转率为25%,HBeAg血清转换率为20%。治疗期间,随访各时间点病毒学突破率为0,肌酸激酶(CK)超过正常上限(ULN)2倍发生率0。血肌酐(Scr)治疗前为(75.1±11.1)μmol/L,治疗48周时为(76.8±10.8)μmol/L,差异无统计学意义(t=0.578,P=0.565)。Scr超过ULN发生率0。骨密度变化发生率0,血磷低于ULN发生率0。结论对于核苷(酸)类药物应答不佳和耐药的CHB患者,TDF单药治疗能有效抑制病毒,且ALT复常率高,不良事件发生率低。

Clinical analysis on tenofovir disoproxil fumarate therapy for 34 nucleos(t)ide-analogue experienced chronic hepatitis B patients

Objective To evaluate the clinical efficacy of tenofovir disoproxil fumarate (TDF) for nucleos (t)ide‐analogue (NAs) experienced chronic hepatitis B (CHB) patients .Methods A total of 34 CHB patients who had been previously treated with NAs and received subsequently TDF for 48 weeks were retrospectively investigated .Among the 34 patients ,18 failed to response to primary treatment ;16 developed antiviral drug resistance ;29 were male and 5 female , with average age as 43 .3 ± 7 .8 years old .Measurement of HBV DNA loading and alanine aminotransferase (ALT ) level were carried out at week 0 ,12 ,24 and 48 ,respectively .The hepatitis B e antigen (HBeAg) seroconversion rate and clinical adverse events rate at week 48 were also recorded .Statistical analyses were performed using standardized mean difference , Student's t‐test and one‐way analysis of variance .Results During the treatment period ,the HBV DNA undetectable rate at week 12 ,24 ,48 are 35 .3% ,67 .6% and 94 .1% ,respectively .The ALT level at week 0 ,12 ,24 ,48 are (63 .9 ± 18 .9) U/L ,(49 .8 ± 11 .9) U/L ,(42 .7 ± 7 .3) U/L and (35 .1 ± 3 .9) U/L ,respectively ,which showed significant differences (F= 36 .3 ,P<0 .05) .At week 48 ,ALT normalization rate ,HBeAg loss rate and HBeAg seroconversion rate were 91 .1% , 25% and 20% ,respectively .During the treatment ,virus breakthrough rate was 0 and creatine kinase levels were no more than 2 times the upper limit of normal .The serum creatinine (Scr) level at week 0 and 48 are (75 .1 ± 11 .1)μmol/L and (76 .8 ± 10 .8)μmol/L ,which showed no significant difference (t=0 .578 ,P=0 .565) .All patients showed a normal level of Scr ,bone mineral density and serum phosphate throughout the treatment period .Conclusion For NAs experienced CHB patients ,TDF can help to efficiently suppress HBV DNA replication and achieve a high rate of ALT normalization with a low rate of adverse events .