长期应用替诺福韦酯对慢性乙型肝炎患者肾脏和骨骼肌肉相关实验室指标的影响

Effects of long-term use of tenofovir on kidney and skeletal muscle related laboratory parameters in patients with chronic hepatitis B

目的 了解长期服用替诺福韦酯对慢性乙型肝炎患者肾脏和骨骼肌肉相关实验室指标的影响.方法 收集2014年1月1日至12月31日在首都医科大学附属北京地坛医院就诊的慢性乙型肝炎患者的病历资料进行回顾性分析.患者均服用替诺福韦酯300 mg,1次/d,持续24个月.用药前和用药3、6、9、12、15、18、21、24个月进行血清肌酐、磷、ALP 和CK水平检测,实验室不良事件定义为血清肌酐较基线值升高≥44.2 μmol/L,连续2次检测（间隔3个月）检测血磷〈0.8 mmol/L,血清ALP〉2倍参考值上限（ULN）,血清CK〉3＆#215;ULN或连续2次检测（间隔3个月）CK〉500 U/L. 结果 纳入分析的患者共40例,男性31例,女性9例;年龄19~59岁,平均（34±11）岁.用药后男性和女性患者血清肌酐水平均呈逐渐升高趋势,但仅男性患者血清肌酐的上升趋势具有统计学意义（P=0.03）;男性和女性患者血磷和血清CK水平与用药前比较差异均无统计学意义（均P〉0.05）.40例患者中1例（2.5%）连续3次检测血磷均〈0.80 mmol/L,确认为实验室不良事件.未发现其他实验室不良事件. 结论 慢性乙型肝炎患者连续2年服用替诺福韦酯可能导致血清肌酐升高和血磷降低,应加强监测;对血清CK水平无明显影响.

Objective Effects of long-term use of tenofovir on kidney and skeletal muscle related laboratory indexes in patients with chronic hepatitis B.Methods The medical record data of patients with chronic hepatitis B in Beijing Ditan Hospital, Capital Medical University from January 1, 2014 to December 31, 2014 were collected and retrospectively analyzed.All patients were given tenofovir 300 mg once daily and lasted for 24 months.The levels of serum creatinine, phosphorus, alkaline phosphates （ALP） and creatine kinase （CK） were tested before medication and 3, 6, 9, 12, 15, 18, and 24 months after medication.The laboratory tests suggestive of adverse events included the following： values of serum creatinine exceeding the baseline value by 44.2 μmol/L, blood phosphorus〈0.8 mmol/L for 2 consecutive times （every 3 months）, serum ALP〉2 times more than the upper limit of normal （ULN） and,serum CK〉3 times more than ULN or CK〉500 U/L for 2 consecutive times （every 3 months）.Results A total of 40 patients were enrolled in this study, including 31 males and 9 females, with a mean age of 34±11 years （19-59 years）.After medication, the serum creatinine levels of all patients gradually increased, but only the trend of male patients was statistically significant （P=0.03）.There was no statistically significant difference in serum phosphorus and CK levels between male and female patients before and after medication （P〉0.05）.Of the 40 patients, 1（2.5%） case was identified as a laboratory adverse event since serum phosphorus 〈0.80 mmol/L for 3 consecutive times.No other laboratory test results suggesting adverse events were found.Conclusions Chronic hepatitis B patients taking tenofovir for two consecutive years might cause increase of serum creatinine and decrease of blood phosphorus, therefore monitoring should be strengthened.The medication had no significant impact on serum CK levels.