3种核苷酸类药物对慢性乙型肝炎患者肾功能的影响及替比夫定对阿德福韦酯所致肾功能损伤的干预效果

Influences of three nucleotide drugs on renal function of patients with chronic hepatitis B and intervention effect of telbivudine on renal function injury caused by adefovir dipivoxil

目的比较替比夫定(LdT)、恩替卡韦(ETV)、阿德福韦酯(ADV)单药治疗对慢性乙型肝炎(CHB)患者肾功能的影响,探讨替比夫定对所致肾功能损伤的干预效果。方法采用随机数字表法将本院收治的309例CHB患者分为LdT组(n=70)、ETV组(n=94)和ADV组(n=145)。另选取本院同期应用ADV治疗后出现轻度肾功能损伤的69例CHB患者,根据后续治疗方案分为ADV转LdT组(n=33)和ADV转ETV组(n=36)。比较5组患者0、48、96、144周时的血清肌酐(SCr)、肾小球滤过率估值(eGFR)水平;比较治疗144周时5组患者SCr和eGFR相对基线变化率;比较治疗144周时5组患者eGFR分布较基线的变化情况。结果治疗0、48、96、144周时,ADV转LdT组SCr水平显著下降,eGFR水平显著升高(P<0.05),而ADV转ETV组SCr、eGFR水平无显著变化。治疗0、48、96、144周时,ADV组、LdT组、ETV组SCr、eGFR水平变化两两比较,差异均有统计学意义(P<0.05)。治疗144周时,LdT组SCr、eGFR相对基线变化率最为显著,特别是在ADV转LdT组中,SCr、eGFR相对基线变化率更为显著。治疗144周时,ADV组、LdT组、ETV组eGFR分布较基线变化显著(P<0.05),且ADV转ETV组与ADV转LdT组比较有显著差异(P<0.05)。结论在应用ADV、LdT、ETV单药治疗CHB患者中,LdT的肾功能保护作用最好,ADV最差,ETV对肾功能无明显影响。对于ADV导致肾功能损伤的患者,应用LdT进行后续治疗可显著改善患者的SCr和eGFR水平,对肾功能有明显的改善作用。

Objective To compare the effects of single application of telbivudine(LdT),entecavir(ETV)and adefovir dipivoxil(ADV)on renal function of patients with chronic hepatitis B(CHB)and to explore the influence of LdT on renal function injury caused by ADV.Methods Totally 309 CHB patients in our hospital were randomly divided into LdT group(n=70),ETV group(n=94)and ADV group(n=145).In addition,69 CHB patients with mild renal injury caused by ADV in the same period were divided into ADV transferring to LdT group(n=33)and ADV transferring to ETV group(n=36)according to the follow-up treatment.The serum creatinine(SCr)and estimated GFR(eGFR)level were compared among the 5 groups at the time points of 0,48,96 and 144 weeks of treatment.At the time point of 144 weeks,the change rates of SCr and eGFR levels relative to baseline levels were compared among 5 groups.At the time point of 144 weeks,the changes of eGFR distribution against baseline were compared among 5 groups.Results At the time points of 0,48,96,and 144 weeks,the level of SCr in the ADV to LdT group decreased significantly,and the level of eGFR increased significantly(P<0.05),but there was no significant change in the levels of SCr and eGFR in the ADV transferring to ETV group.At the time points of 0,48,96,144 weeks,there were significant differences in levels of SCr and eGFR among ADV group,LdT group and ETV group(P<0.05).At the time point of 144 weeks,the change rates of SCr and eGFR in LdT group was the most significant,especially in the ADV to LdT group.At the time point of 144 weeks,there were significant differences in distribution of eGFR when compared with those of baseline in ADV group,LdT group and ETV group(P<0.05),and there was a significant difference between the ADV transferring to ETV group and the ADV transferring to LdT group(P<0.05).Conclusion Among the CHB patients treated with single application of ADV,LdT and ETV,LdT shows the best protective effect on renal function,ADV is the worst and ETV shows no significant effect on renal function.For patients with renal impairment caused by ADV,application of LdT as a subsequent treatment can significantly improve the levels of SCr and eGFR as well as renal function.