94例中草药相关肝损伤患者的临床及预后分析

Clinical and Prognostic Analysis of 94 Patients with Herb-Induced Liver Injury

目的:通过分析94例中草药相关肝损伤(HILI)患者的一般特征、临床表现、实验室指标、肝组织病理及影响预后的因素,更好地指导相关中草药的合理用药,降低药物性肝损伤的发病率。方法:回顾性分析2018年1月至2019年12月就诊于某医院诊断为HILI患者的一般资料、中草药用药史、基础疾病、临床表现、实验室指标、肝组织病理、治疗及影响预后的因素。结果:本研究中94例HILI患者年龄分布为14~80岁,其中女性60例,男性34例,以41~60年龄段居多。HILI患者以黄疸及消化道症状最常见,主要为尿黄(42例,44.7%)、黄疸(34例,36.2%)、恶心(27例,28.7%)、腹痛(20例,21.3%)、乏力(11例,11.7%)、陶土样便(5例,5.3%),少数出现发热(7例,7.4%)、皮疹(2例,2.1%)等全身性反应。HILI患者临床分型以肝细胞损伤型(77例,81.9%)最常见,其次是胆汁淤积型(11例,11.7%)、混合型(6例,6.4%)。94例HILI患者经治疗后85例(90.4%)好转出院,8例(8.5%)未愈出院,1例(1.1%)进展为失代偿期肝硬化。经统计分析年龄、临床分型、INR、Alb对预后有统计学意义,而性别、吸烟史、BMI、ALT、AST、TBIL、DBIL、ALP、GGT对预后无统计学意义,多因素分析Alb可能是预后的独立预测指标。结论:中草药相关肝损伤发病率呈逐年上升趋势,引起肝损伤的中草药种类繁多,以何首乌、土三七、雷公藤较为常见。HILI多发生于中老年女性,其临床表现无特异性,以黄疸、尿黄为主,HILI临床分型以肝细胞损伤型为主,HILI患者的肝组织病理无明显特异性,多数伴有嗜酸性粒细胞浸润、中央静脉周围肝细胞点灶状坏死及肝细胞凋亡小体。HILI患者大多数预后较好,极少数预后不良进展为肝衰竭或失代偿期肝硬化。

Objective: To analyze the general characteristics, clinical manifestations, laboratory indicators, liver histopathology and prognostic factors of 94 patients with herb-induced liver injury, so as to guide the rational use of relevant Chinese herbal medicine and reduce the incidence of drug-induced liver injury. Methods: The general data of HILI patients diagnosed at the Affiliated Hospital of Qingdao University from January 2018 to December 2019 were analyzed retrospectively, including clinical manifestations, basic diseases, laboratory indicators, liver histopathology and prognostic factors. Results: In this study, the age distribution of 94 HILI patients was 14~80 years old, including 60 females and 34 males, mostly in the age group of 41~60. Symptoms of jaundice and digestive symptoms were most common in HILI patients, mainly including urine yellow (42 cases, 44.7%), jaundice (34 cases, 36.2%), nausea (27 cases, 28.7%), abdominal pain (20 cases, 21.3%), fatigue (11 cases, 11.7%), grey stools (5 cases, 5.3%), and a few systemic reactions such as fever (7 cases, 7.4%) and rash (2 cases, 2.1%). The most common clinical type of HILI patients was hepatocellular (77 cases, 81.9%), followed by cholestatic (11 cases, 11.7%) and mixed type (6 cases, 6.4%). Of the 94 HILI patients, 85 (90.4%) were discharged from hospital after treatment, 8 (8.5%) were discharged from hospital without recovery, and 1 (1.1%) developed decompensated cirrhosis. After statistical analysis, age, clinical types, Alb and INR had statistical significance for prognosis, while gender, smoking history, BMI, ALT, AST, TBIL, DBIL, ALP and GGT had no statistical significance for prognosis. Multivariate analysis of Alb may be an independent predictor of prognosis. Conclusion: The incidence of herb-induced liver injury is on the rise year by year. There are many kinds of Chinese herbal medicines causing liver injury, such as Polygonum multiflorum, Tunopanax notoginseng and Tripterygium wilfordii. HILI mostly occurs in middle-aged and elderly women, and its clinical manifestations are non-specific, mainly jaundice and urinary yellow. The most common clinical type of HILI is hepatocellular. The liver histopathology of HILI patients has no obvious specificity, most of which are accompanied by eosinophil infiltration, focal hepatocyte necrosis around the central vein, and hepatocyte apoptosis bodies. Most patients with HILI have a good prognosis, with a small minority progressing to hepatic failure or decompensated cirrhosis.