药物性肝损伤100例临床病理分析

目的探讨药物性肝损伤(DILI)患者的临床病理学特点,为临床诊治提供病理依据。方法选择行肝穿刺确诊DILI病例100例(男:女=48:52),年龄(33.04±14.00)岁,分为急性DILI组(39例)和慢性DILI组(61例)。肝组织行HE、组织化学染色和免疫组织化学染色,进行临床病理观察分析。结果致DILI的药物种类中,中药类占21%,激素类药物占11%。其中78%的患者出现血清ALT升高和(或)胆红素升高,急性DILI组ALT异常和高胆红素发生率均高于慢性DILI组(56.41%与34.43%,x2=4.69,P<0.05),且程度也明显较重(P<0.01)。急性DILI组和慢性DILI组病理改变,除纤维化和胆管增生外,其余差异无统计学意义。DILI的相对病理特点主要表现为:中央静脉周围为主的肝细胞坏死,富含中性粒细胞和嗜酸性粒细胞的炎性细胞浸润,肝细胞和(或)毛细胆管性淤胆,小泡性脂肪变性为主的混合性肝细胞脂肪变性,上皮样肉芽肿结构等。结论包括中药在内的DILI在中国大陆地区已非少见,中药应用需进一步规范。DILI有其相对临床病理特点,在临床诊治中要注意临床表现与病理特点的密切结合。

Clinical and pathological analysis of 100 cases of drug-induced liver injury

Objective To study the clinical and pathological features of drug-induced liver injury (DILI). Methods Liver specimens were obtained through needle biopsies from 100 patients with DILI. The histological preparations of the specimens were stained with haematoxylin eosin, several histochemistry methods, and immunohistochemistry stains. The pathological changes of the livers were analyzed together with the patients's clinical data. The patients were divided into two groups, an acute DILI group (n = 39) and a chronic DILI group (n = 61), based on their clinical courses and histological changes in their livers. In the chronic DILI group, the clinical courses were longer than 6 months and/or fibrosis or cirrhosis occurred in their liver tissues. Results Among our cases the leading cause of DILI was Chinese herb medicine, accounting for 21% of the 100 cases; steroids induced cases were 11% of the total. 78% of the patients presented elevated serum transaminases and/or jaundice. The degree of transaminases elevation and the frequency of jaundice happening in the acute group were significantly higher than those in the chronic group (P < 0.05). The histopathological liver changes in these DILI cases included: (1) necrosis commonly occuned in acinar zone 3, (2) abundant neutrophil and/or eosinophil infiltrations, (3) hepatocytic and/or canalicular cholestasis with little or no inflammation, (4) microvesicular steatosis mixed with macrovesicular steatosis, and (5) presentation of epitheloid cell granuloma. There were no significant differences in liver histopathology between the acute and the chronic DILI groups, except that the fibrosis and the ductular proliferation were different. Conclusion DILI has become a notable liver disease in mainland China, and the use of Chinese herbal medicine must be improved, standardized and regulated more closely.