ライフサイエンスコーパス: DILI

1 DILI also occurred in 1 of 9480 patients taking diclofen

2 DILI associated with SJS/TEN is rare and associated with

3 DILI had a primary role in 68 (64%), a contributory role

4 DILI is an uncommon indication for hospitalization carry

5 DILI leads directly or indirectly to fatality in 7.6% of

6 DILI may be attenuated or exacerbated by pathogens depen

7 DILI was caused by a single prescription medication in 7

8 DILI with cirrhosis yielded the highest in-hospital and

9 Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (2

10 ring n = 354 drugs, an algorithm to assign a DILI score was developed.

11 te liver failure (controls) collected from a DILI Biobank in Germany.

12 For these purposes, a DILI ontology (DILIo) was developed by using the Unified

13 ased on daily dose, lipophilicity, and RM, a DILI score algorithm was developed that provides a scale

14 Acetaminophen DILI yielded lower risks of mortality (HR 0.24, 95 % CI:

15 for prediction of prognosis during an acute DILI event.

16 At 6 months after DILI onset, 18.9% of the 598 evaluable subjects had pers

17 ularly when fatalities occur >26 weeks after DILI onset.

18 N-acetylcysteine may be protective against DILI while taking antituberculosis medication.

19 Prediction of prognosis among DILI patients using the Model for End-Stage Liver Diseas

20 hout adverse effects (n = 55 and n = 92) and DILI patients (n = 98, n = 28, and n = 143) were assayed

21 ap of histologic findings exists for AIH and DILI, sufficient differences exist so that pathologists

22 relationship between hepatic metabolism and DILI of prescription medications.

23 amoxicillin-clavulanate as outpatients, and DILI occurred in 1 of 2350 (43 of 100,000; 95% CI, 24-70

24 ationship between calculated DILI scores and DILI risk was obtained when applied to three independent

25 Conclusion: Frequencies of SOS and DILI after inotuzumab ozogamicin treatment were 1.5% and

26 ght network investigators and categorized as DILI having a primary, a contributory, or no role in the

27 prospective study used two methods to assess DILI causality: a structured expert opinion process and

28 e molecular features important for assessing DILI risk.

29 eliable, and reproducible means of assessing DILI causality is still needed.

30 with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.

31 When applied at DILI recognition, the nR criteria for Hy's Law provides

32 We analyzed data collected at DILI recognition and at the time of peak levels of alani

33 i-tuberculosis drug induced liver injury (AT-DILI).

34 NAC should be considered in management of AT-DILI.

35 time to ALT&100 U/L in participants with AT-DILI, but significantly reduced length of hospital stay.

36 f DILI can help with predicting and avoiding DILI in clinical practice and provide the foundation for

37 Because DILI is a diagnosis of exclusion, selected elements of t

38 46 nevirapine-induced rash plus 3 with both DILI and SJS phenotype) and 155 age-, sex- and ethnicity

39 ore, a clear relationship between calculated DILI scores and DILI risk was obtained when applied to t

40 assessing the likelihood of an agent causing DILI and written criteria for improving the reliability,

41 ibiotics remain the most common drug causing DILI in the United States and Europe.

42 >1000 drugs for their likelihood of causing DILI in humans, of which >700 drugs were classified into

43 patients with clinically well-characterized DILI [n = 35, including 19 hepatocellular injury (HC) an

44 Chronic DILI may occur, but development of clinically important

45 nt were independent risk factors for chronic DILI (C-statistic = 0.71).

46 no-DILI drugs in comparison with the 2-class DILI model.

47 e developed and compared 2-class and 3-class DILI prediction models using the machine learning algori

48 quantitative assessment of risk of clinical DILI.

49 exposure thresholds associated with clinical DILI.

50 -approved drugs by extracting all clinically DILI-related histopathologic descriptions for 1082 liver

51 Conclusion: DILI is an uncommon cause of ALF that evolves slowly, af

52 a foundation for future studies correlating DILI pathology with its causality and outcome.

53 llance is the most useful tool for detecting DILI, and prompt discontinuation of the drug responsible

54 We identified patients who developed DILI in association with SJS/TEN from a registry of DILI

55 may still be the better method of diagnosing DILI compared with an objective tool such as the Roussel

56 ients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (d

57 During DILI, oncotic necrosis with concomitant release and reco

58 tic regression analyses the algorithm (i.e., DILI score model) defined the relative contribution of d

59 not only had a higher resolution to estimate DILI risk but also showed an improved capability to diff

60 Although an infrequent event, DILI from antidepressant drugs may be irreversible, and

61 stically to promote sex bias in experimental DILI by reducing Tregs.

62 terms were "liver injury," "liver failure," "DILI," "hepatitis," "hepatotoxicity," "cholestasis," and

63 ailure (28% versus 9%, P = 0.004), and fatal DILI (23% versus 4%, P = 0.001), but not jaundice (46% v

64 ver failure, liver transplantation, or fatal DILI.

65 ver failure, liver transplantation, or fatal DILI.

66 66,399 markers in 51 cases of flucloxacillin DILI and 282 controls matched for sex and ancestry.

67 nsights into the mechanism of flucloxacillin DILI and have the potential to substantially improve dia

68 interesting example is flucloxacillin (FLUX)-DILI, which is associated with the HLA-B*57:01 allele.

69 At present, the mechanism of FLUX-DILI is not understood, but the HLA association suggests

70 Causality assessment for DILI and SJS/TEN was carried out with the Roussel Uclaf

71 ption has been proposed as a risk factor for DILI from medications, but there is insufficient evidenc

72 lar target but differ in their potential for DILI.

73 e developed a polygenic risk score (PRS) for DILI by aggregating effects of numerous genome-wide loci

74 ean ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A*02:01 and D

75 an appropriate means of estimating risk for DILI compared with dose alone.

76 There is an unmet need to predict risk for DILI more reliably, and lipophilicity might be a contrib

77 s to be associated with significant risk for DILI; however, the RO2 failed to estimate grades of DILI

78 elopment of new or adapted model systems for DILI prediction.

79 Mortality from DILI is significantly higher in individuals with pre-exi

80 Liver samples from DILI patients contained more activated JNK, predominantl

81 Proposed scales for grading DILI severity and assessing the likelihood of an agent c

82 bjects were deemed by expert opinion to have DILI; 81.1% were considered highly likely, 15.0% probabl

83 tivity was generally correlated across human DILI concern categories.

84 a affirm that severe manifestations of human DILI are multifactorial, highly associated with combinat

85 l testing regimes for the detection of human DILI thus remain inadequate.

86 nt of predictive preclinical models of human DILI.

87 ere highly associated with more severe human DILI, more restrictive product safety labeling related t

88 rs contribute to the susceptibility to human DILI and its severity that are either compound- and/or p

89 o be more useful than miR-122 in identifying DILI patients, and K18, OPN, and MCSFR are promising can

90 Idiosyncratic DILI is a relative rare hepatic disorder but can be seve

91 Idiosyncratic DILI was shown to have an important dose-dependency and

92 l prescription medications and idiosyncratic DILI.

93 We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that e

94 Furthermore, idiosyncratic DILI is not a single disease entity but rather a spectru

95 opulations on the incidence of idiosyncratic DILI (iDILI) that may develop independently of drug dose

96 We describe here cases of idiosyncratic DILI ALF enrolled during a 10.5-year period.

97 inical models for the study of idiosyncratic DILI and its pathogenesis is poorly understood.

98 isk factors, and mechanisms of idiosyncratic DILI.

99 mmune regulation contribute to idiosyncratic DILI.

100 iated any genetic factors with idiosyncratic DILI.

101 factoring RM into the RO2 to highly improve DILI prediction.

102 he most robust increase in plasma miR-122 in DILI and it correlated with the highest ALT levels.

103 ate biomarkers were significantly altered in DILI cases compared with healthy volunteers.

104 n approach for evaluating liver histology in DILI and demonstrate numerous associations between patho

105 ghlighted processes previously implicated in DILI, including unfolded protein responses and oxidative

106 alth products (NHPs) have been implicated in DILI.

107 cellular) cholestasis were more prevalent in DILI (CS) (P < 0.02).

108 es will help further delineate their role in DILI diagnosis and management.

109 Transplant-free survival in DILI ALF is determined by the degree of liver dysfunctio

110 current nomenclature and terminology used in DILI research.

111 d with the exosome-rich fraction, whereas in DILI/APAP injury these miRNAs were present in the protei

112 sociation between azithromycin and increased DILI in patients with chronic liver disease.

113 xiclav (amoxicillin-clavulanic acid) induced DILI.

114 3%), idiosyncratic drug-induced liver injury DILI (22%), acute hepatitis B virus infection (12%), aut

115 Drug-induced liver injury (DILI) accounts for 20-40% of all instances of clinical h

116 ogy and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using cu

117 imal in detecting drug-induced liver injury (DILI) and predicting its outcome.

118 the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes.

119 he association of drug-induced liver injury (DILI) and Stevens-Johnson syndrome (SJS) or toxic epider

120 ited States, with drug-induced liver injury (DILI) being the single most common reason for regulatory

121 Drug-induced liver injury (DILI) developed in 26 (7.9%) InO recipients and 3 (1%) c

122 ith incidences of drug-induced liver injury (DILI) for more than 50 years, although its role in this

123 Patients with drug-induced liver injury (DILI) frequently have comorbid conditions, but the effec

124 Distinguishing drug-induced liver injury (DILI) from idiopathic autoimmune hepatitis (AIH) can be

125 he role of JNK in drug-induced liver injury (DILI) in liver tissue from patients and in mice with gen

126 the incidence of drug-induced liver injury (DILI) in the general population.

127 Drug-induced liver injury (DILI) is a leading cause of drug failure in clinical tri

128 d development and drug-induced liver injury (DILI) is a leading cause of preclinical and clinical dru

129 Drug-induced liver injury (DILI) is a leading cause of termination in drug developm

130 Drug-induced liver injury (DILI) is a main cause of drug withdrawal.

131 Drug-induced liver injury (DILI) is a major health issue, as it remains difficult t

132 Drug-induced liver injury (DILI) is a major public health concern, and improving it

133 Drug induced liver injury (DILI) is a necro-inflammatory liver disease caused by se

134 Drug-induced liver injury (DILI) is a patient-specific, temporal, multifactorial pa

135 Idiosyncratic drug-induced liver injury (DILI) is a rare disease that develops independently of d

136 Idiosyncratic drug-induced liver injury (DILI) is a rare disorder that is not related directly to

137 Idiosyncratic drug-induced liver injury (DILI) is a rare, often difficult-to-predict adverse reac

138 Drug-induced liver injury (DILI) is an adverse reaction to drugs or other xenobioti

139 Idiosyncratic drug-induced liver injury (DILI) is an important but relatively infrequent cause of

140 Drug-induced liver injury (DILI) is an important cause of acute liver failure, with

141 Drug induced liver injury (DILI) is an important cause of acute liver injury and ac

142 Drug-induced liver injury (DILI) is an important cause of death and indication for

143 Drug-induced liver injury (DILI) is an important cause of serious liver disease.

144 Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion.

145 and management of drug-induced liver injury (DILI) is hindered by the limited utility of traditional

146 Drug-induced liver injury (DILI) is largely a diagnosis of exclusion and is therefo

147 Drug-induced liver injury (DILI) is the leading cause of liver failure in the Unite

148 Idiosyncratic drug-induced liver injury (DILI) is traditionally thought not to be dose-related.

149 Drug-induced liver injury (DILI) limits the development and application of many the

150 Drug-induced liver injury (DILI) may present any morphologic characteristic of acut

151 on idiosyncratic drug-induced liver injury (DILI) over the past 2 years in the peer-reviewed literat

152 Drug-induced liver injury (DILI) presents a significant challenge to drug developme

153 Drug-induced liver injury (DILI) remains a leading cause of drug withdrawal from hu

154 URPOSE OF REVIEW: Drug-induced liver injury (DILI) remains an important disease in clinical practice.

155 ith idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibilit

156 Immune-mediated, drug-induced liver injury (DILI) triggered by drug haptens is more prevalent in wom

157 at hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is use

158 (acetaminophen, APAP)-induced liver injury (DILI), and Toll-like receptor (TLR) 9+4 ligand-induced i

159 e pathogenesis of drug-induced liver injury (DILI), but supporting data are limited.

160 y lead to serious drug-induced liver injury (DILI), chronic liver disease, or acute liver failure.

161 lure (ALF) due to drug-induced liver injury (DILI), though uncommon, is a concern for both clinicians

162 increased risk of drug-induced liver injury (DILI).

163 mainly caused by drug-induced liver injury (DILI).

164 t drugs can cause drug-induced liver injury (DILI).

165 RNA biomarker for drug-induced liver injury (DILI).

166 concerns, such as drug-induced liver injury (DILI).

167 rechallenge after drug-induced liver injury (DILI): antimicrobials; and central nervous system, cardi

168 ersensitivity (15 drug-induced liver injury [DILI], 33 SJS/TEN, 20 hypersensitivity syndrome, and 46

169 This perspective outlines many of the known DILI mechanisms and assessment methods used to evaluate

170 ibitory properties of 24 Most-DILI-, 28 Less-DILI-, and 20 No-DILI-concern drugs were investigated.

171 ified into three categories (most-DILI, less-DILI, and no-DILI).

172 d provide a pharmaceutical strategy to limit DILI and improve drug safety.

173 eir role in a mouse model of immune-mediated DILI.

174 ssment methods used to evaluate and mitigate DILI risk.

175 To model DILI, we immunized BALB/c, BALB/cBy, IL-6-deficient, and

176 ificant hepatic metabolism should cause more DILI than those without it.

177 -LTKB), the inhibitory properties of 24 Most-DILI-, 28 Less-DILI-, and 20 No-DILI-concern drugs were

178 were classified into three categories (most-DILI, less-DILI, and no-DILI).

179 an improved capability to differentiate most-DILI drugs from no-DILI drugs in comparison with the 2-c

180 s of 24 Most-DILI-, 28 Less-DILI-, and 20 No-DILI-concern drugs were investigated.

181 ree categories (most-DILI, less-DILI, and no-DILI).

182 ity to differentiate most-DILI drugs from no-DILI drugs in comparison with the 2-class DILI model.

183 Nonetheless, DILI is challenging to investigate because of its rarity

184 of the blood transcriptome for biomarkers of DILI.

185 ranscriptome might provide new biomarkers of DILI.

186 ing analyses are under way to study cases of DILI attributed to a single medication.

187 ntribute similarly in many clinical cases of DILI.

188 e ultimate aim of preventing future cases of DILI.

189 etabolism have been implicated as a cause of DILI, and their formation has been correlated to the add

190 al agent flucloxacillin is a common cause of DILI, but the genetic basis for susceptibility remains u

191 drugs and are also the most common cause of DILI.

192 The most common causes of DILI were acetaminophen (35.0 %) and anti-tuberculous dr

193 f mechanisms and clinical characteristics of DILI.

194 A definitive diagnosis of DILI is, nowadays, one of the main challenging issue in

195 The diagnosis of DILI relies on the exclusion of other aetiologies of liv

196 stablished but poorly understood etiology of DILI.

197 We describe our experience of DILI occurring in association with SJS/TEN including the

198 patic DNA accumulation is a novel feature of DILI pathogenesis.

199 c accuracy, but the histological features of DILI and their relationship to biochemical parameters an

200 s descriptors of histopathologic features of DILI.

201 useful, particularly in the emergent form of DILI related to immune-checkpoint inhibitors in patients

202 ver, it is now evident that certain forms of DILI are immune-mediated and may involve the activation

203 lism are associated with higher frequency of DILI.

204 y of SOS, but a relatively high frequency of DILI.

205 owever, the RO2 failed to estimate grades of DILI severity.

206 f 1.32 pM that enabled the identification of DILI.

207 th drugs associated with a high incidence of DILI (flucloxacillin, amoxicillin, isoniazid, and nitros

208 ion-based study in Iceland, the incidence of DILI was the highest reported to date.

209 es of patients with short vs long latency of DILI.

210 Defining lexemes of DILI histopathology would allow the development of advan

211 the diagnosis, prediction and management of DILI will be reviewed.

212 e sensitive to more severe manifestations of DILI than drugs that only have a single liability factor

213 MicroRNAs are a potential marker of DILI.

214 specifically related to known mechanisms of DILI (like mitochondrial and BSEP inhibition), and, alon

215 unction protein, is an essential mediator of DILI by showing that mice deficient in Cx32 are protecte

216 rgo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients h

217 Within 6 months of DILI onset, 30 patients received liver transplants (4.5%

218 death or transplantation within 6 months of DILI onset.

219 d diagnostic criteria regarding the onset of DILI, evolution of liver injury, risk factors, and manda

220 We assessed incidences and outcomes of DILI including associated factors for mortality.

221 The pathogenesis of DILI is not fully understood.

222 s into the mechanisms of the pathogenesis of DILI.

223 establishing the diagnosis and prognosis of DILI were reviewed.

224 The crude annual incidence rate of DILI was 19.1 (95% confidence interval [CI], 15.4-23.3)

225 At recognition of DILI, the R- and nR-based models identified patients who

226 association with SJS/TEN from a registry of DILI patients from a single center.

227 CL accurately identified patients at risk of DILI after acetaminophen overdose (area under ROC curve

228 d the incidence and the quantitative risk of DILI in a population-based cohort.

229 The role of DILI in these fatalities is poorly characterized, partic

230 de crucial insights into the mechanism(s) of DILI with the ultimate aim of preventing future cases of

231 rovides a scale of assessing the severity of DILI risk in humans associated with oral medications.

232 or other etiologies, causes, and severity of DILI.

233 ics of pathophysiology and susceptibility of DILI can help with predicting and avoiding DILI in clini

234 of the pathophysiology and susceptibility of DILI.

235 Hepatocellular type of DILI is more common in younger patients, whereas cholest

236 cell-cell interactions in specific types of DILI.

237 models and the mechanistic understanding of DILI, and proposes our vision of a roadmap for the devel

238 e, will harmonize and accelerate research on DILI.

239 estasis yielded an AUC of 0.91 in predicting DILI (CS) versus AIH.

240 teristic curve (AUROC) of 0.90 in predicting DILI (HC) versus AIH.

241 the rule-of-two performed best in predicting DILI in seven therapeutic categories.

242 to have definite, highly likely, or probable DILI.

243 ts with definite, highly likely, or probable DILI.

244 performance characteristics of 14 promising DILI biomarker candidates.

245 ategies used by medicinal chemists to reduce DILI risk during the optimization of drug candidates.

246 in liver pathways, predicting human-relevant DILI using in vitro human liver models is crucial.

247 inically important liver injury after severe DILI is rare.

248 ohorts, can be used to predict a more severe DILI outcome.

249 ver Injury Network, DILIGEN, and the Spanish DILI registry) are important tools for clinical and gene

250 ts with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012.

251 Due to logistical barriers, gold standard DILI screening fails to be executed at the point-of-care

252 within 6 months of presenting with suspected DILI (6-month mortality) for 306 patients enrolled in th

253 l networks enrolling patients with suspected DILI according to standardized methodologies are needed.

254 n in 2003 to recruit patients with suspected DILI and create a repository of biological samples for a

255 es obtained from 249 patients with suspected DILI enrolled in the prospective, observational study co

256 using data from 247 patients with suspected DILI enrolled in the same study at the University of Nor

257 data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer.

258 Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 8

259 Among 250 patients with suspected DILI, the expert opinion adjudication process scored 78

260 laboratory data from patients with suspected DILI.

261 6-month mortality in patients with suspected DILI.

262 within 6 months for patients with suspected DILI.

263 Of 598 eligible Swedish DILI cases, 9% belonged to the < or =10 mg/day group, 14

264 , liver diseases, drug targets and long-term DILI.

265 but were more severe in AIH (P < 0.05) than DILI (HC).

266 ammation scores were more severe in AIH than DILI (CS) (P </= 0.05).

267 The DILI score model was also functional with drug pairs def

268 ly, for drug pairs where the RO2 failed, the DILI score correctly identified toxic drugs.

269 Standardization of the DILI nomenclature and methods to assess causality, along

270 dify hepatic metabolism and excretion of the DILI-causative agent leading to cellular stress, cell de

271 's LiverTox database to demonstrate that the DILI score correlated with the severity of clinical outc

272 umbers may provide a therapeutic approach to DILI.

273 ility factors that predispose individuals to DILI.

274 The most common drugs leading to DILI in the United States are antibiotics, central nervo

275 mpound-specific primary mechanisms linked to DILI include: cytotoxicity, reactive metabolite formatio

276 The PRS predicted the susceptibility to DILI in patients treated with fasiglifam, amoxicillin-cl

277 scored the polygenic architecture underlying DILI vulnerability at the level of hepatocytes, thus fac

278 properties and clinical dose provide useful DILI predictivity.

279 ts and retrospective analyses using verified DILI-associated drugs from the Liver Tox Knowledge Base

280 ential hallmarks to differentiate AIH versus DILI.

281 cytopenia were independently associated with DILI fatalities.

282 rt or long latencies are not associated with DILI mortality.

283 %), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21-1.56; P = 1.5

284 eosinophilia has often been associated with DILI, although its role remains unclear.

285 and a stronger independent association with DILI fatalities within 26 weeks compared to the original

286 cted data from 96 individuals diagnosed with DILI in Iceland from 2010 through 2011 (54 women; median

287 e association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls).

288 We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from

289 We studied liver sections from patients with DILI (due to acetaminophen, phenprocoumon, nonsteroidal

290 Multicenter databases of patients with DILI (the United States Drug Induced Liver Injury Networ

291 outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective stud

292 Among 748 consecutive patients with DILI from 1997 to March 2015, 36 (4.8%) had associated f

293 ducting a prospective study of patients with DILI in the United States.

294 iR-122 isomiRs in the serum of patients with DILI that were at low concentration or not present in he

295 Of the 771 patients with DILI, 32 developed ALF.

296 rbidity burden and outcomes of patients with DILI, and developed and validated a model to calculate r

297 on-based study of hospitalized patients with DILI.

298 a model for predicting ALF in patients with DILI.

299 uced more isomiRs, particularly rapidly with DILI.

300 ransfer from naive female mice to those with DILI reduced hepatitis severity and hepatic IL-6.