类风湿性关节炎患者应用雷公藤制剂及合并用药所致药物性肝损伤的临床特征分析

Clinical features of drug-induced liver injury due to Tripterygium wilfordii preparation and concomitant medications in patients with rheumatoid arthritis

目的观察分析类风湿性关节炎患者使用雷公藤制剂及合并用药发生药物性肝损伤(DILI)的临床特征。方法回顾性收集2014年1月—2019年12月于洪湖市中医院使用雷公藤制剂及合并用药所致DILI的112例类风湿性关节炎患者的临床资料,观察人口统计学资料及DILI的临床特征,并探讨合并用药和基础疾病对DILI的影响。计量资料多组间及进一步两两比较采用Kruskal-Wallis H检验。结果患者平均年龄为(48.13±14.38)岁,女性81例(72.32%),在合并基础疾病中以非酒精性脂肪性肝病较为多见,共8例(7.14%),在联合用药中以雷公藤制剂中药联合非甾体消炎药(NSAID)/抗风湿药物(DMARD)多见,共70例(62.50%)。患者主要临床表现为关节痛,共110例(98.21%)。102例(91.07%)为肝脏生化学检查异常;RUCAM评分为6~8分的患者有66例(58.93%),110例(98.21%)为轻度肝损伤(1级);通过保肝治疗(均<6个月),所有患者肝功能均好转,无加重及死亡。雷公藤制剂+糖皮质激素+NSAID/DMARD联用组(n=22)的血清ALP、GGT较雷公藤制剂+NSAID/DMARD联用组(n=70)显著升高(P值均<0.05)。合并非酒精性脂肪性肝病组患者(n=8)较无基础疾病组(n=90)患者血清ALT升高更显著(P<0.05)。结论类风湿性关节炎患者可因用雷公藤制剂及合并用药发生DILI,以中年女性居多,临床表现以关节痛为主,肝功能损伤较轻,无明显慢性化,预后较好。联合使用糖皮质激素和NSAID/DMARD的患者,或者合并非酒精性脂肪性肝病基础疾病的患者,肝损伤更严重。

Objective To investigate the clinical features of drug-induced liver injury(DILI)due to Tripterygium wilfordii preparation and concomitant medications in patients with rheumatoid arthritis(RA).Methods A retrospective analysis was performed for the clinical data of 112 RA patients with DILI caused by Tripterygium wilfordii preparations and concomitant medications who were treated in Honghu Hospital of Traditional Chinese Medicine from January 2014 to December 2019,and demographic data and the clinical features of DILI were observed to explore the influence of concomitant medications and underlying diseases on DILI.The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups and further comparison between two groups.Results All 112 patients had a mean age of 48.13±14.38 years,and there were 81 female patients(72.32%).The most common underlying disease was nonalcoholic fatty liver disease(NAFLD)in 8 patients(7.14%),and as for concomitant medications,70 patients(62.50%)were treated with Tripterygium wilfordii preparation combined with non-steroid anti-inflammatory drug(NSAID)or disease-modifying anti-rheumatic drug(DMARD).The main clinical manifestation was joint pain in 110 patients(98.21%).Among the 112 patients,102(91.07%)had abnormal results of liver biochemical examinations;66 patients(58.93%)had an RUCAM score of 6-8 points,and 110 patients(98.21%)had mild(grade 1)liver injury.After liver-protecting treatment(for less than 6 months in all patients),all patients had an improvement in liver function without aggravation or death.The Tripterygium wilfordii preparation+glucocorticoid+NSAID/DMARD group with 22 patients had significant increases in the serum levels of alkaline phosphatase(ALP)and gamma-glutamyl transpeptidase(GGT)compared with the Tripterygium wilfordii preparation+NSAID/DMARD group with 70 patients(P<0.05).The 8 patients with NAFLD had a significantly greater increase in serum alanine aminotransferase compared with the 90 patients without underlying diseases(P<0.05).Conclusion RA patients may develop DILI due to Tripterygium wilfordii preparation and concomitant medications,which is commonly observed in middle-aged women.Joint pain is the main clinical manifestation,and patients tend to have mild liver injury and good prognosis without marked chronicity.More severe liver injury is observed in patients with combined medication of glucocorticoids and NSAID/DMARD or those with the underlying disease of NAFLD.