title: Necrotic cell death and suppression of T-cell immunity characterized acute liver failure due to drug-induced liver injury.
abstract: 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.
authors.affiliation: Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan. Electronic address: keikaki@iwate-med.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kakisaka
authors.affiliation: Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan.
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Kuroda
authors.affiliation: Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takikawa
mesh_terms: D017209:Apoptosis; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood; D005260:Female; D006501:Hepatic Encephalopathy / Q000209:etiology; D019693:Hepatitis, Autoimmune / Q000209:etiology; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D007249:Inflammation; D007564:Japan / Q000453:epidemiology; D008099:Liver / Q000166:cytology / Q000473:pathology*; D017114:Liver Failure, Acute / Q000209:etiology / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D009336:Necrosis; D011795:Surveys and Questionnaires; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; C066855:HGF protein, human; D017228:Hepatocyte Growth Factor
keywords: ALF, acute liver failure; DILI, drug-induced liver injury; HGF