核苷(酸)类抗肝炎药物对慢性乙型肝炎住院患者肝肾功能的影响

目的：分析核苷（酸）类抗肝炎药物（NAs）对慢性乙型肝炎患者肝肾功能的影响，为临床合理用药提供参考。方法：综合应用某院临床药学管理系统（PASS PharmAssist）、病案质控监测系统和中国医院药物警戒系统检索病历，回顾性分析某院2017年1月至2018年6月因患慢性乙型肝炎而采用NAs药物治疗的患者病例。利用SPSS 23.0软件，采用正态分布、t检验、卡方检验进行单因素分析，把符合单因素分析（P<0.05）的协变量纳入二元logistic分析，以考察多种协变量对NAs药物诱导患者肝肾功能变化的影响。结果：收集到因患慢性乙型肝炎而服用抗肝炎药物的患者病例116份，其中包括男性79例（68.1%），女性37例（31.9%），肝功能正常者65例，慢性肝功能不全者51例。在肝功能不全组，NAs药物性肝损加重发生率为17.65%（9/51），时间为用药后4~13 d；在肝功能正常组，NAs药物性肝损伤发生率为4.61%（3/65），时间为用药后15~19 d。此外，研究表明NAs药物对肝脏的安全性为恩替卡韦 > 拉米夫定 > 阿德福韦酯 > 替比夫定 > NAs药物联用。在116例患者中肾功能正常者74例，慢性肾功能不全者42例，在肾功能不全组发现患者因服用NAs药物导致血清肌酐升高发生率为14.29%（6/42），时间为用药后2~10 d，在肾功能正常组未发现NAs药物性肾损伤者。此外，研究表明NAs药物对肾脏的安全性为：NAs药物联用，拉米夫定，阿德福韦酯 > 恩替卡韦 > 替比夫定，相关因素分析表明NAs药物性肝损伤的发生与患者的肝功能不全（OR=5.344，95% CI：1.349-21.167）（P=0.017）有关。结论：NAs药物对患者肝功能和肾功能确实有影响，主要发生在肝功能不全患者身上，但对肝功能正常的患者影响较小。此外，核苷（酸）类抗肝炎药物中拉米夫定对肝脏和肾脏的安全性相对较高。研究结果提示临床在治疗肝功能不全的患者时，应注意调整NAs药物品种或给药剂量并监测患者肝功能指标变化，以确保用药安全。

Effect of nucleoside (acid) anti-hepatitis drugs on liver and kidney function in hospitalized patients with chronic hepatitis B

OBJECTIVE To analyze the effects of nucleoside (acid) anti-hepatitis drugs (NAs) on liver and kidney function in patients with chronic hepatitis B,and provide reference for clinical rational drug use. METHODS The medical records of patients with chronic hepatitis B who were treated with NAs from January 2017 to June 2018 in a hospital were retrospectively analyzed using PASS PharmAssist, medical record quality control monitoring system and Chinese hospital pharmacovigilance system. Univariate analysis was performed using normal distribution, t-test, and chi-square test by SPSS 23.0 software. Covariates that met the univariate analysis (P<0.05) were included in the binary logistic analysis to investigate the effect of multiple covariates on the changes of liver and kidney function induced by NAs drugs. RESULTS One hundred and sixteen patients with chronic hepatitis B were enrolled, including 79 males (68.1%), 37 females (31.9%), among which 65 with normal liver function and 51 with chronic liver dysfunction. In the liver dysfunction group, the incidence of drug-induced liver damage was 17.65% (9/51), and the onset time was 4 to 13 days after administration. In the normal liver function group, the incidence of drug-induced liver injury was 4.61% (3/65), and the time is 15-19 d after medication. In addition, studies have shown that the safety of NAs drugs for the liver is entecavir > lamivudine > adefovir dipivoxil > telbivudine > NAs drugs. Among the 116 patients, 74 had normal renal function and 42 had chronic renal insufficiency. In the renal insufficiency group, the incidence of serum creatinine elevation was by 14.29% (6/42) due to NAs, and the time was 2-10 days after medication. No NAs drug-induced kidney injury was found in the normal renal function group.In addition, the renal safety of NAs was demonstrated as follows:combination of NAs, lamivudine, adefovir dipivoxil > entecavir > telbivudine.Correlation analysis showed that the occurrence of drug-induced liver damagewas associated withhepatic insufficiency(OR=5.344, 95% CI:1.349-21.167) (P=0.017). CONCLUSION NAs do have an effect on liver and renal function, mainly in patients with liver dysfunction, but less in patients with normal liver function.In addition, lamivudine in nucleos (t) ide antihepatitis drugs has a relatively favorable safe profile for liver and kidney.The results suggest that in clinical treatment of patients with liver dysfunction, attention should be paid to adjusting the variety or dose of NAs and monitoring the changes of liver function indicators to ensure the safety of medication.