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台湾药物性肝损伤的临床特征与结局:着重探讨慢性乙型肝炎感染的影响

Clinical characteristics and outcomes of drug-induced liver injury in Taiwan: With emphasis on the impact of chronic hepatitis B infection.

作者信息

Huang Yi-Shin, Tseng Shao-Yu, Chen Wen-Wen, Chang Ting-Tsung, Peng Cheng-Yuan, Lo Gin-Ho, Hsu Chao-Wei, Hu Chi-Tan, Huang Yi-Hsiang

机构信息

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC.

Taiwan Drug Relief Foundation, Taipei, Taiwan, ROC.

出版信息

J Chin Med Assoc. 2022 Mar 1;85(3):286-294. doi: 10.1097/JCMA.0000000000000648.

Abstract

BACKGROUND

Whether hepatitis B virus (HBV) infection can affect the outcomes of drug-induced liver injury (DILI) is controversial. This study aimed to evaluate the characteristics and outcomes of DILI in Taiwan, with an emphasis on the impact of HBV infection.

METHODS

We prospectively recruited patients with DILI from multiple centers in Taiwan from 2010 to 2018.

RESULTS

A total of 1,014 patients were enrolled. The leading culprit drug category was antimicrobials (481, 47.4%), followed by nonsteroidal anti-inflammatory drugs, anticonvulsants, and statins. Among the antimicrobials, antituberculosis agents were most likely to induce liver injury (257, 25.3%), followed by antibacterial, antifungal, and antiviral agents. The liver-related mortality rate was 8.2% (83/1,014). The patients who died had higher rates of hepatocellular-type liver injury, elevated liver biochemical tests, preexisting liver cirrhosis, jaundice, chronic HBV infection, and antituberculosis drug-induced liver injury (ATDILI) than the survivors. A total of 131 patients (12.9%) with DILI were HBV carriers, of whom 23 (17.6%) died of hepatic failure. The rate of HBV-DNA > 2000 IU/mL was higher in the patients who died (47.8% vs. 26.9%, p = 0.047) than in the survivors. After adjusting for possible risk factors, active HBV infection with HBV-DNA > 2000 IU/mL was the most significant risk factor for liver-related mortality (adjusted HR, 4.40, 95% CI, 2.31%-8.38%, p < 0.001). The other independent risk factors for mortality were ATDILI and albumin-bilirubin (ALBI) score (adjusted HR, 1.25 and 4.09, respectively, p < 0.003).

CONCLUSION

Antituberculosis agents were the leading cause of DILI in Taiwanese, and they were associated with poorer outcomes than other drug categories. Active HBV infection, ATDILI and ALBI score were independent risk factors for fatal DILI. Close monitoring of liver tests and timely antiviral therapy should be implemented in HBV carriers during the administration of high-risk drugs, such as antituberculosis agents.

摘要

背景

乙型肝炎病毒(HBV)感染是否会影响药物性肝损伤(DILI)的结局存在争议。本研究旨在评估台湾地区DILI的特征和结局,重点关注HBV感染的影响。

方法

我们于2010年至2018年从台湾多个中心前瞻性招募DILI患者。

结果

共纳入1014例患者。主要的致病药物类别为抗菌药物(481例,47.4%),其次是非甾体抗炎药、抗惊厥药和他汀类药物。在抗菌药物中,抗结核药物最易导致肝损伤(257例,25.3%),其次是抗菌、抗真菌和抗病毒药物。肝脏相关死亡率为8.2%(83/1014)。死亡患者的肝细胞型肝损伤、肝脏生化检查指标升高、既往存在肝硬化、黄疸、慢性HBV感染及抗结核药物性肝损伤(ATDILI)的发生率均高于存活患者。共有131例(12.9%)DILI患者为HBV携带者,其中23例(17.6%)死于肝衰竭。死亡患者中HBV-DNA>2000 IU/mL的比例高于存活患者(47.8%对26.9%,p=0.047)。在调整可能的危险因素后,HBV-DNA>2000 IU/mL的活动性HBV感染是肝脏相关死亡的最显著危险因素(调整后HR,4.40,95%CI,2.31%-8.38%,p<0.001)。其他独立的死亡危险因素为ATDILI和白蛋白-胆红素(ALBI)评分(调整后HR分别为1.25和4.09,p<0.003)。

结论

抗结核药物是台湾地区DILI的主要病因,与其他药物类别相比,其结局较差。活动性HBV感染、ATDILI和ALBI评分是致命性DILI的独立危险因素。在使用抗结核药物等高风险药物期间,应对HBV携带者密切监测肝功能检查并及时进行抗病毒治疗。

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