Kakisaka Keisuke, Kataoka Kojiro, Suzuki Yuji, Okada Yohei, Yoshida Yuichi, Kuroda Hidekatsu, Takikawa Yasuhiro
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan.
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan.
Cytokine. 2016 Oct;86:21-28. doi: 10.1016/j.cyto.2016.07.010. Epub 2016 Jul 19.
BACKGROUND & AIMS: The aim of this study was to investigate the clinical characteristics and pathophysiology of drug-induced liver injury (DILI) - acute liver failure (ALF).
The patients with acute liver injury (ALI) including ALF from 2009 to 2014 were analyzed. The hepatic encephalopathy (HE) development rate was compared with the findings from a national survey in Japan. The serum cytokines levels and the findings of a liver function test were evaluated in the DILI patients.
The HE development rate substantially decreased for autoimmune hepatitis (AIH) - and undetermined cause-induced ALI owing to the early prediction system, but not in DILI-ALI. Among the DILI-ALF and AIH-ALF cases, the CK-18 fragment (1480.1U/L, 3945.4U/L), IL-8 (82.9pg/mL, 207.5pg/mL), IP-10 (1379.6pg/mL, 3731.2pg/mL) and MIP-1β (1017.7pg/mL, 2273.3pg/mL) levels were lower in the DILI-ALF cases. Among the DILI-ALI and DILI-ALF cases, IL-4 (19.8pg/mL, 25.4pg/mL) and RANTES (14028.0pg/mL, 17804.7pg/mL) were higher in DILI-ALI, and HMGB-1 (397.1pg/μL, 326.2pg/μL) and HGF (2.41ng/mL, 0.55ng/mL) were higher in DILI-ALF. We observed that HGF independently associated with DLI-ALF development.
Despite the low grade apoptosis and inflammation, DILI patients progressed to ALF comparable with that of the AIH patients.
本研究旨在调查药物性肝损伤（DILI）-急性肝衰竭（ALF）的临床特征及病理生理学。
对2009年至2014年患有包括ALF在内的急性肝损伤（ALI）患者进行分析。将肝性脑病（HE）的发生率与日本全国调查结果进行比较。对DILI患者的血清细胞因子水平及肝功能检查结果进行评估。
由于早期预测系统，自身免疫性肝炎（AIH）及病因不明所致ALI的HE发生率大幅下降，但DILI-ALI患者未下降。在DILI-ALF和AIH-ALF病例中，DILI-ALF病例的细胞角蛋白18片段（1480.1U/L，3945.4U/L）、白细胞介素-8（82.9pg/mL，207.5pg/mL）、干扰素诱导蛋白10（1379.6pg/mL，3731.2pg/mL）和巨噬细胞炎性蛋白-1β（1017.7pg/mL，2273.3pg/mL）水平较低。在DILI-ALI和DILI-ALF病例中，DILI-ALI患者的白细胞介素-4（19.8pg/mL，25.4pg/mL）和调节激活正常T细胞表达和分泌因子（RANTES，14028.0pg/mL，17804.7pg/mL）较高，而DILI-ALF患者的高迁移率族蛋白B1（HMGB-1，397.1pg/μL，326.2pg/μL）和肝细胞生长因子（HGF，2.41ng/mL，0.55ng/mL）较高。我们观察到HGF与DILI-ALF的发生独立相关。
尽管DILI患者的凋亡和炎症程度较低，但进展为ALF的情况与AIH患者相当。
