1.Department of Medical Service; 3. Department of Hepatological Surgery,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China; 2. Liver Disease Department,Hebei Hospital of Traditional Chinese Medicine for Liver Disease,Hebei 050800,China; 4. Department of Integrative Medicine,the Fifth Medical Center,Chinese PLA General Hospital,Beijing 100039,China
摘要目的 分析179例肝组织活检诊断药物性肝损伤的肝功能异常患者临床特征。方法 回顾性分析2010-01至2015-01解放军总医院第五医学中心收治的符合条件的诊断为肝功能异常且可排除甲乙丙戊型病毒性肝炎、EB病毒及CMV病毒性感染、自身免疫性肝病、酒精性肝病、非酒精性脂肪性肝病,以及遗传代谢性肝病导致的肝损伤病例179例。依据肝组织活检病理结果将病例分为急性/亚急性组和慢性组,分析两组间临床特征及病理表现差异。结果 在发病类型方面,急性/亚急性肝损伤以青年为主(64.3%),而对于慢性肝损伤以老年为主(53.7%),差异具有统计学意义(P<0.05)。临床症状表现中,乏力、肝区不适、发热、皮肤瘙痒方面,两组之间相比差异无统计学意义;而急性/亚急性组中纳差(50.0% vs 30.9%)和尿黄(58.9% vs 35.0%)症状较慢性组更明显(P<0.05)。肝功能生化检测指标方面,急性/亚急性组在ALT、AST、TBIL、DBIL方面明显高于慢性组,有统计学差异(P<0.01),但两组在ALP、GGT、ANA的分布比例无统计学差异。急性/亚急性组与慢性组药物性肝损伤的病理表现不同,两组在胆汁淤积病理表现方面没有差异,而急性/亚急性组多见于混合型病理表现,慢性组多见肝细胞损伤病理表现。结论 老年人易发生慢性药物性肝损伤,并且多以肝细胞损伤病理表现为主,对于病因不明的反复肝功能异常老年患者,应警惕慢性药物性肝损伤的可能。
Abstract:Objective To explore the clinical features of drug-induced liver injury(DILI) in patients diagnosed by liver biopsy.Methods A retrospective study was conducted of 179 patients treated at the Fifth Medical Center of Chinese PLA General Hospital between January 2010 and January 2015. All of them had abnormal liver function and were diagnosed with drug-induced liver injuries by liver biopsy that were caused by factors other than common liver disease, including hepatitis A, B, C, E, virus EB, CMV virus infection, autoimmunity liver disease, alcoholic liver disease, nonalcoholic fatty hepatopathy and genetic metabolic liver disease. These patients were assigned to two groups according to liver biopsy results to analyze clinical features and results of biopsy.Results The acute/subacute group consisted of mainly young patients(64.3%), while in the chronic group, elder patients accounted for 53.7%(P<0.05). In terms of clinical manifestations, such as fatigue, liver discomfort, fever and skin pruritus, there was no difference between those two groups (P>0.05).Poor appetite(50.0% vs 30.9%) and dark urine(58.9% vs 30.5%) were much more common in the acute/sub-acute group than in the chronic group(P<0.05). In terms of biochemical detection of liver function, levels of ALT, AST, TBIL and DBIL were significantly higher in the acute/sub-acute group than in the chronic group (P<0.01), but there was no obvious difference in terms of ALP, GGT or ANA. There was no difference in manifestations of cholestasis biopsy between the two groups. The acute/subacute group had more biopsy manifestations of the mixed type while the chronic liver injury group had more cases of hepatocellular injury.Conclusions The seniors are vulnerable to chronic drug-induced liver injuries, especially i hepatocellular injuries. Patients with recurring and hepatic dysfunction for unknown reasons must be alert to potential chronic drug-induced liver injuries.
Sumeet K A, Harshad D, John E, et al. Burden of liver diseases in the world[J]. Hepatology, 2019, 70(1):151-157 .
[2]
Chalasani N P, Hayashi P H, Bonkovsky H L, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol, 2014, 109(7): 950-967.
[3]
Lu R J, Zhang Y, Tang F L, et al. Clinical characteristics of drug-induced liver injury and related risk factors [J]. ExpTher Med, 2016, 12(4): 2606-2616.
[4]
Lee B M, Lee W C, Jang J Y, et al. Clinical features of drug-induced liver injury according to etiology [J]. J Korean MedSci, 2015, 30(12): 1815-1820.
[5]
Aithal G P, Watkins P B, Andrade R J, et al. Case definition and phenotype standardization in drug-induced liver injury[J]. Clin Pharmacol Ther, 2011, 89(6): 806-815.
[6]
Chen Minjun, Bisgin H, Tong Lillian,et al. Toward predictive models for drug induced liver injury in humans:are we there yet [J]. Biomarkers Med,2014,8(2):201-213.
[7]
Kubo S, Matsuzaki K, Sek T, et al.Severe acute hepatitis in a printing company worker: a case study[J]. J Occup Health, 2015,57(1):87-90.
[8]
Davern T J. Drug -induced liver disease [J] . Clin Liver Dis ,2012,16(2):231-245.