Shigeto Eriko
Department of Respiratory Medicine, National Hospital Organization, Higashihiroshima Medical Center, Hiroshima, Japan.
Kekkaku. 2007 May;82(5):467-73.
To clarify the incidence and clinical significance of anti-tuberculosis drug-induced liver injury.
Questionnaire was sent out by mail to 114 hospitals, to ask whether there were patient(s) from 1994 to 2003 with liver injury induced by anti-tuberculosis drugs with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level of more than 1000 IU/l and/or total bilirubin level of more than 2 mg/dl. As for the cases of severe hepatic injury, their backgrounds and clinical courses were investigated.
Seventy cases were reported from 24 out of 68 hospitals which treated at least 8095 tuberculosis patients in 2003. Incidence rate of severe liver injury by anti-tuberculosis drugs was 0.50 to 0.59 percent in three hospitals with good surveillance system, and overall incidence was estimated to be between 0.1 to 0.5 percent. We could analyze 33 cases; one was HB antigen positive, one had HCV positive liver cirrhosis, 2 had other hepatic disease, and 17 had other underlying disease including diabetes mellitus. Twenty-three were treated by regimens with isoniazid (INH), rifampicin (RFP) and pyrazinamide (PZA), and 8 by regimens without PZA but with INH and RFP and one was a multidrug-resistant case and was treated by regimen with ethionamide and PZA. The onset of liver injury was within 2 months after starting anti-tuberculosis chemotherapy in 28 (85%) cases. In twenty-eight cases which both ALT and total bilirubin level are known, total bilirubin level at the onset of liver injury was more than 2 mg/dl in 14 cases and most of the cases were hepatocellular type of liver injury. Six out of 10 cases with total bilirubin level more than 5 mg/dl died by liver failure. Total birilubin was less than 2 mg/gl in two of the dead cases; in one case antituberculosis drug were continued despite elevated level of ALT and another case complicated with gastric bleeding. Treatment for liver injury was conservative in most cases, 6 were treated by plasmapheresis and no liver transplantation was carried out. Eight cases died of liver failure, one died of tuberculosis and only 15 were treated successfully for tuberculosis.
Incidence rate was high comparared with that by other drugs reported previously. The risk factor of liver injury by antituberculosis drugs was not detected, but elevated total bilirubin level more than 5 mg/dl was an alarming sign for poor prognosis.
阐明抗结核药物所致肝损伤的发生率及临床意义。
通过邮件向114家医院发放问卷，询问1994年至2003年间是否有抗结核药物所致肝损伤患者，其丙氨酸氨基转移酶（ALT）或天冬氨酸氨基转移酶（AST）水平超过1000 IU/L和/或总胆红素水平超过2 mg/dl。对于严重肝损伤病例，调查其背景及临床病程。
2003年至少治疗8095例结核病患者的68家医院中有24家报告了70例。在三家监测系统良好的医院中，抗结核药物所致严重肝损伤的发生率为0.50%至0.59%，总体发生率估计在0.1%至0.5%之间。我们能够分析33例；1例乙肝抗原阳性，1例丙肝阳性肝硬化，2例有其他肝脏疾病，17例有其他基础疾病包括糖尿病。23例采用异烟肼（INH）、利福平（RFP）和吡嗪酰胺（PZA）方案治疗，8例采用不含PZA但含INH和RFP的方案治疗，1例为耐多药病例，采用乙硫异烟胺和PZA方案治疗。28例（85%）肝损伤发生在开始抗结核化疗后2个月内。在28例同时已知ALT和总胆红素水平的病例中，可以发现，肝损伤发生时总胆红素水平超过2 mg/dl的有14例，且大多数病例为肝细胞型肝损伤。总胆红素水平超过5 mg/dl的10例病例中有6例死于肝衰竭。2例死亡病例的总胆红素低于2 mg/gl；1例尽管ALT水平升高仍继续使用抗结核药物，另1例并发胃出血。大多数肝损伤病例采用保守治疗，6例采用血浆置换治疗，未进行肝移植。8例死于肝衰竭，1例死于结核病，仅15例成功治愈结核病。
与先前报道的其他药物相比，发生率较高。未发现抗结核药物所致肝损伤的危险因素，但总胆红素水平超过5 mg/dl是预后不良的警示信号。
