255例肝穿刺证实的慢性药物性肝损伤患者预后的影响因素分析

Influencing factors for the prognosis of biopsy proven patients with chronic drug-induced liver injury:An analysis of 255 cases

目的探讨成人慢性药物性肝损伤(DILI)患者预后的影响因素。方法选取2014年1月—2018年12月于解放军总医院第五医学中心经肝穿刺明确诊断为慢性DILI患者255例,根据2年后患者的肝功能水平分为未恢复组和恢复组。统计两组患者的年龄、性别、BMI、用药种类、DILI损伤分型、DILI损伤严重程度、合并基础疾病、实验室指标、肝组织学结果及2年预后等临床资料。正态分布的计量资料两组间比较采用t检验;非正态分布的计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ^(2)检验。采用logistic单因素及多因素回归分析慢性DILI预后的独立影响因素。结果经过两年的随访,195例患者肝功能恢复(76.5%),60例(23.5%)未恢复。两组患者在肝损伤类型(P=0.028)、合并糖尿病(P=0.048)比例以及肝组织纤维化程度(P<0.001)的差异具有统计学意义,且未恢复组患者基线WBC、PLT、ALT、AST、GGT和总胆汁酸水平明显高于恢复组患者,ChE水平低于恢复组患者(P值均<0.05)。将基线特征纳入单因素分析logistic回归,结果显示PLT、ALT、AST、ChE、肝纤维化程度分级对预后的影响具有统计学意义(P值均<0.05)。上述变量的多因素logistic回归分析结果显示,PLT<100×10^(9)/L(OR=3.592,95%CI:1.128~11.438,P=0.003)、ALT>2×ULN(OR=3.080,95%CI:1.331~7.127,P=0.009)是慢性DILI预后的独立危险因素。结论当患者达慢性DILI诊断标准时,基线PLT<100×10^(9)/L、ALT>2×ULN作为独立危险因素,可以用于筛选出更易出现不良预后的患者。

Objective To investigate the influencing factors for the prognosis of adult patients with chronic drug-induced liver injury(DILI).Methods A total of 255 patients who were diagnosed with chronic DILI by liver biopsy in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to December 2018 were enrolled,and according to the liver function after 2 years,they were divid-ed into non-recovery group and recovery group.The two groups were analyzed in terms of the clinical data including age,sex,body mass index,types of drugs used,type of DILI injury,severity of DILI injury,underlying diseases,laboratory markers,liver histology,and 2-year prognosis.The t-test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.Univariate and multivariate logistic regression analyses were used to investigate the independent risk factors for the prognosis of chronic DILI.Results After 2 years of follow-up,195 patients(76.5%)achieved the recovery of liver func-tion,while 60 patients(23.5%)did not achieve such recovery.There were significant differences between the two groups in the type of DILI injury(P=0.028),the proportion of patients with diabetes(P=0.048),and the degree of liver fibrosis(P<0.001),and com-pared with the recovery group,the non-recovery group had significantly higher levels of baseline white blood cell count,platelet count(PLT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transpeptidase,and total bile acid and a significantly lower level of cholinesterase(ChE)(all P<0.05).The baseline characteristics were included in the univariate logistic regression analysis,and the results showed that PLT,ALT,AST,ChE,and fibrosis degree were significantly associated with the prognosis of chro-nic DILI(all P<0.05).The multivariate logistic regression analysis of the above variables showed that PLT<100×10^(9)/L(odds ratio[OR]=3.592,95%confidence interval[CI]:1.128-11.438,P=0.003)and ALT>2×upper limit of normal(ULN)(OR=3.080,95%CI:1.331-7.127,P=0.009)were independent risk factors for the prognosis of chronic DILI.Conclusion When patients meet the diagnostic criteria for chronic DILI,the independent risk factors PLT<100×10^(9)/L and ALT>2×ULN may be used to screen out the pa-tients who are more likely to have poor prognosis.