临床诊断的肝细胞型急性药物性肝损伤患者血清ALT/ALP比值变化特点与组织病理学特征分析

目的 探讨药物性肝损伤(DILI)患者临床分型的变化及其组织病理学特征。方法 2018年8月～2019年8月入院临床诊断为肝细胞型DILI患者43例,在入院治疗2周后行肝穿活检,在病理学检查当日再次根据临床指标确定临床分型,观察组织病理学特征。结果 43例临床诊断的肝细胞型DILI患者在肝穿时血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血清总胆红素(TBIL)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)和总胆汁酸(TBA)水平已显著降低,其R值较入院时也显著下降(19.6±13.6对3.29±3.26),差异具有统计学意义(P<0.05);组织病理学检查诊断急性炎症型21例,炎症淤胆型22例;在入院时,急性炎症型与炎症淤胆型患者血清ALT、AST、TBIL、ALP和GGT水平无显著性差异(P>0.05),仅急性炎症型患者R值显著小于炎症淤胆型(13.8±6.2对25.5±16.5,P=0.004),血清TBA水平显著低于炎症淤胆型(61.0±60.8 μmol/L对115.3±80.9μmol/L,P=0.017);入院时诊断为肝细胞型DILI的43例患者在肝穿时仅9例符合肝细胞型临床分型;经ROC曲线分析,以R值等于14.9为截断点,其曲线下面积(AUC)为0.708,具有一定的诊断意义。结论 药物性肝损伤的临床分型会随着病情的变化而呈动态变化,入院时以较高的R值诊断胆汁淤积具有一定的指导意义,值得进一步观察。

Serum ALT/ALP ratio changes and histopathological features of patients with drug-induced liver injury acute hepatocellular type

Objective The purpose of this study was to summarize serum alanine aminotransferase(ALT)/alkaline phosphatase(ALP)ratio changes and liver histopathological features of patients with drug-induced liver injury(DILI)acute hepatocellular type.Methods 43 patients with DILI were admitted to Beijing You'an Hospital between August 2018 and August 2019 and diagnosed at presentation as acute hepatocellular type by serum ALT,ALP and R.All patients underwent liver biopsies at the end of two week liver-protecting treatment.Results At the time of liver biopsies,serum ALT,aspartate aminotransferase(AST),total serum bilirubin(TBIL),ALP,γ-glutamyltranspeptidase(GGT)and total bile acid(TBA)levels in 43 clinically diagnosed at admission as hepatocellular type of DILI decreased greatly,and the R also decreased from 19.6±13.6 to 3.29±3.26(P<0.05);the histopathological examination showed acute inflammation in 21 and inflammatory cholestasis in 22 cases;there were no significant differences as respect to serum ALT,AST,TBIL,ALP and GGT levels at presentation between the two groups(P>0.05),while the R in patients with acute inflammation was much lower than in patients with inflammatory cholestasis(13.8±6.2 vs.25.5±16.5,P=0.004),and serum TBA level was also significantly lower than in patients with inflammatory cholestasis(61.0±60.8μmol/L vs.115.3±80.9μmol/L,P=0.017);only 9 patients accorded with hepatocellular injury at liver biopsies out of the 43 patients with DILI;the area under ROC was 0.708 in diagnosing intrahepatic cholestasis,when the R equalto 14.9 was set as the cut-off-value.Conclusion The clinical type classification of drug-induced liver injury presents as a dynamic changes,and the increased R might help diagnose intrahepatic cholestasis.