老年患者药物性肝损伤的病因分布与病情严重程度的影响因素

摘要/Abstract

摘要： 目的探讨老年药物性肝损伤(DILI)药物病因分布及影响病情严重程度相关因素,并分析其肝组织病理学特征。方法收集并分析联勤保障部队第904医院和青岛市市立医院收治的86例老年DILI患者临床资料。根据病情严重程度分为轻度组(n=51)和重度组(n=35)。比较两组一般资料、基础疾病、用药情况及实验室指标等。对40例患者进行肝组织病理学检查(轻度组24例,重度组16例),比较两组肝组织学改变。采用多因素logistic回归分析评估老年DILI发生重度损伤的独立危险因素。结果 86例患者共涉及161种可疑致病药物,其中单独用药47例(54.6%),多重用药39例(45.4%)。与轻度组比,重度组合并恶性肿瘤比例更高[42.9% vs. 21.6%],多重用药比例增加[62.9% vs. 37.3%](P<0.05)。重度组ALT、AST及ALP水平明显高于轻度组[ALT:465(266,814)U/L vs. 214(123,394)U/L;AST:398(211,697)U/L vs. 178(95,312)U/L;ALP:212(142,390)U/L vs. 165(94,280)U/L](P<0.05)。同时重度组TBil、INR及Scr水平显著升高[TBil:(92.5±25.7)μmol/L vs. (28.4±6.3)μmol/L;INR:(1.3±0.3) vs. (1.1±0.2);Scr:(97.8±17.6)μmol/L vs. (82.5±11.4)μmol/L],而Alb水平明显降低[(35.6±5.3)g/L vs. (39.2±4.1)g/L](P<0.05)。肝组织病理学结果显示,重度组肝细胞坏死评分(1.7±0.5)分 vs.(0.9±0.3)分、炎症活动度评分(1.9±0.7)分vs.(1.1±0.4)分、气球样变评分(1.2±0.3)分vs.(0.6±0.2)分、脂肪变性程度(19.7±5.1)分vs.(14.5±3.2)分及肝纤维化评分(2.0±0.6)分 vs.(1.2±0.4)分均高于轻度组(P<0.05),且胆汁淤积发生率更高(62.5% vs. 25.0%,P<0.05)。多因素logistic回归分析显示,年龄、合并恶性肿瘤、多重用药、TBil升高、INR升高及肝纤维化评分升高为老年DILI发生重度损伤的独立危险因素,而Alb升高为保护因素(P<0.05)。结论老年DILI患者的病情严重程度与年龄、恶性肿瘤、多重用药及肝功能损害指标等因素密切相关。重度DILI患者常表现为更明显的肝细胞坏死、炎症反应及纤维化改变,并伴胆汁淤积。

关键词: 药物性肝损伤, 老年, 病情严重程度, 肝组织病理学, 危险因素

Abstract: Objective To investigate the distribution of causative drugs in elderly patients with drug-induced liver injury (DILI) and to analyze the factors associated with disease severity, as well as the histopathological characteristics of liver tissue. Methods The clinical data of 86 elderly patients with DILI treated at the No. 904 Hospital of the Joint Logistics Support Force and Qingdao Municipal Hospital were retrospectively collected and analyzed. According to the severity of the disease, patients were divided into a mild group (n=51) and a severe group (n=35). Differences in general characteristics, underlying diseases, medication status, and laboratory indicators between the two groups were compared. Liver histopathological examination was performed in 40 patients (24 in the mild group and 16 in the severe group), and the histological changes between the two groups were analyzed. Multivariate logistic regression analysis was used to identify independent risk factors associated with severe DILI in elderly patients. Results A total of 161 suspected causative drugs were identified among the 86 patients, including single-drug use in 47 cases (54.6%) and multiple-drug use in 39 cases (45.4%). Compared with the mild group, the severe group had a higher proportion of patients with malignant tumors[42.9% vs. 21.6%] and a higher proportion of multiple drug use[62.9% vs. 37.3%] (P<0.05). Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were significantly higher in the severe group than in the mild group[ALT: 465 (266, 814) U/L vs. 214 (123, 394) U/L; AST: 398 (211, 697) U/L vs. 178 (95, 312) U/L; ALP: 212 (142, 390) U/L vs. 165 (94, 280) U/L] (P<0.05). Meanwhile, total bilirubin (TBil), international normalized ratio (INR), and serum creatinine (Scr) levels were significantly increased in the severe group[TBil: (92.5±25.7) μmol/L vs. (28.4±6.3) μmol/L; INR: (1.3±0.3) vs. (1.1±0.2); Scr: (97.8±17.6) μmol/L vs. (82.5±11.4) μmol/L], whereas albumin (Alb) levels were significantly lower[(35.6±5.3) g/L vs. (39.2±4.1) g/L] (P<0.05). Liver histopathological results showed that the scores of hepatocyte necrosis (1.7±0.5 vs. 0.9±0.3), inflammatory activity (1.9±0.7 vs. 1.1±0.4), ballooning degeneration (1.2±0.3 vs. 0.6±0.2), the degree of steatosis (19.7±5.1 vs. 14.5±3.2), and liver fibrosis (2.0±0.6 vs. 1.2±0.4) were all higher in the severe group than in the mild group (P<0.05), and the incidence of cholestasis was also significantly higher (62.5% vs. 25.0%, P<0.05). Multivariate logistic regression analysis indicated that age, malignant tumors, multiple drug use, elevated TBil, elevated INR, and increased liver fibrosis score were independent risk factors for severe DILI in elderly patients, whereas higher Alb levels were a protective factor (P<0.05). Conclusion The severity of DILI in elderly patients is closely associated with age, malignant tumors, multiple drug use, and indicators of liver function injury. Severe DILI is often characterized by more pronounced hepatocyte necrosis, inflammatory responses, and fibrosis, accompanied by cholestasis.

Key words: Drug-induced liver injury, Elderly, Disease severity, Liver histopathology, Risk factors

刘敏, 左丹, 苗瑞田, 高妍芬. 老年患者药物性肝损伤的病因分布与病情严重程度的影响因素[J]. 肝脏, 2026, 31(6): 891-895.

Liu Min, Zuo Dan, Miao Ruitian, Gao Yanfen. Etiological distribution and factors influencing disease severity in elderly patients with drug-induced liver injury[J]. Chinese Hepatolgy, 2026, 31(6): 891-895.

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