ライフサイエンスコーパス: ACLF

1 ACLF displays key features of systemic inflammation and

2 ACLF grade and white cell count, were independent predic

3 ACLF is especially severe in patients with no prior hist

4 ACLF mortality is associated with loss of organ function

5 ACLF patients had lower human leukocyte antigen-DR isoty

6 ACLF resolved or improved in 49.2%, had a steady or fluc

7 ACLF serum was depleted in LPCs with up-regulated LPA le

8 ACLF was associated with a significant increase of Enter

9 ACLF was defined as two or more extrahepatic organ failu

10 ACLF was more common in the younger patients and in thos

11 rrhosis with (n = 178) and without (n = 101) ACLF from the CANONIC study of the CLIF consortium.

12 ients without (80%) than in those with (20%) ACLF.

13 A total of 80 ACLF patients undergoing <5 L paracentesis were randomiz

14 A total of 80 ACLF patients undergoing <5 L paracentesis were randomiz

15 In patients without a prior history of AD, ACLF was unexpectedly characterized by higher numbers of

16 Both SNPs were protective against ACLF; IL-1beta (odds ratio [OR], 0.34, 95% confidence in

17 ALD-ACLF also increased by 206.3% (348-1,066 registrants; P

18 The majority of patients with EASL-alone ACLF have preserved liver function, suggesting the need

19 n bilirubin level at diagnosis of EASL-alone ACLF was 2.0 mg/dL (interquartile range: 1.1-4.0).

20 monstrated a rising trend in mortality among ACLF-3 patients at 7 days (18.0%), 14 days (27.7%), and

21 proportion was greatest for patients with an ACLF-3 score and MELD-Na score below 25 (43.8% at 28 day

22 On multivariate analysis, ACLF was not significantly associated with eGFR less tha

23 HRS (odds ratio, 4.2; 95% CI, 1.2-14.8), and ACLF (odds ratio, 5.9; 95% CI, 1.3-25.9).

24 For assessing hemostasis in Non-ACLF and ACLF patients the underlying dataset shows advantages of

25 ere outside the normal range in Non-ACLF and ACLF patients, but were significantly more aberrant in A

26 in (Tf) and ceruloplasmin levels in ACLF and ACLF-MOF, compared to patients with cirrhosis and contro

27 ted, acutely decompensated without ACLF, and ACLF).

28 The short-term course of AD and ACLF (worsening, improvement, stable) correlated closely

29 trations were higher in patients with AD and ACLF and correlated with Model for End-Stage Liver Disea

30 predicted mortality in patients with AD and ACLF.

31 ients between compensated cirrhosis, AD, and ACLF, as well as patients with and without complications

32 s the utility of LT in patients with ALF and ACLF.

33 the interaction between MELD-Na category and ACLF-3 showed that patients with ACLF-3 had greater risk

34 Cirrhosis and ACLF represent a substantial and increasing health and e

35 in patients with decompensated cirrhosis and ACLF, with special emphasis on the principal features of

36 th 90-day mortality were: P: age, gender and ACLF type; I: drug, infection, surgery, and variceal ble

37 Baseline CysC is a biomarker of RD, HRS, and ACLF and an independent predictor of mortality in patien

38 fails to predict development of RD, HRS, and ACLF.

39 t (WL) inclusion to predict WL mortality and ACLF.

40 dian follow-up, 783 developed EASL and APASL ACLF, 4,296 developed EASL ACLF alone, and 574 developed

41 ped EASL ACLF alone, and 574 developed APASL ACLF alone.

42 The 28-day and 90-day mortalities for APASL ACLF were 41.9% and 56.1%, respectively, and were 37.6%

43 The incidence rate of APASL ACLF was 5.7 per 1,000 person-years (95% confidence inte

44 OFs, 33.7% (300 patients) were diagnosed as ACLF.

45 We assessed ACLF grades at different time points to define disease r

46 ver failure (total bilirubin >/=12 mg/dL) at ACLF diagnosis.

47 Because ACLF patients have greater hemodynamic derangements than

48 mortality, and identify differences between ACLF and AD.

49 (28-day) and mid-term (90-day) mortality by ACLF grade at 3-7 days.

50 y patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic informat

51 center European Chronic Liver Failure (CLIF) ACLF in Cirrhosis study.

52 We sought to compare ACLF incidence and mortality among a diverse cohort of p

53 tors of course severity were CLIF Consortium ACLF score (CLIF-C ACLFs) and presence of liver failure

54 Conversely, ACLF-NR cMon featured elevated expression of inflammator

55 e organ failure and mortality data to define ACLF grades, assess mortality, and identify differences

56 between patients who did vs did not develop ACLF and patients who did vs did not die during hospital

57 had ACLF when the study began, 112 developed ACLF, and 928 did not have ACLF.

58 Of the 602 patients analyzed, 88 developed ACLF (15%), 43 died in the hospital (7%), and 72 died wi

59 h the highest baseline KP activity developed ACLF during follow-up.

60 Fifty-six (31%) patients developed ACLF, 54 (30%) underwent LT and 35 (19%) died.

61 y began was 33.9%, among those who developed ACLF was 29.7%, and among those who did not have ACLF wa

62 etabolites identified patients who developed ACLF with an AUC of 0.84 (95% confidence interval [CI] 0

63 thelial dysfunction induced by sepsis drives ACLF through HGF-C/EBPbeta pathway.

64 ed EASL and APASL ACLF, 4,296 developed EASL ACLF alone, and 574 developed APASL ACLF alone.

65 pectively, and were 37.6% and 50.4% for EASL ACLF.

66 I]: 5.4-6.0), and the incidence rate of EASL ACLF was 20.1 (95% CI: 19.5-20.6).

67 Patients had either ACLF (n = 41), acute decompensation of cirrhosis without

68 re (ACLF) with three or more organs failing (ACLF-3) portends low survival without transplantation, w

69 have high rates of acute-on-chronic failure (ACLF) development and high mortality within 30 days of a

70 ACLF) and in acute-on-chronic liver failure (ACLF) by CCT and ROTEM including agreement of both tests

71 Acute-on-chronic liver failure (ACLF) develops in patients with chronic liver disease an

72 who develop acute-on-chronic liver failure (ACLF) have poor outcomes after liver transplantation.

73 Acute-on-chronic liver failure (ACLF) in cirrhosis is an increasingly recognized syndrom

74 Acute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensat

75 ion (AD) and acute-on-chronic liver failure (ACLF) in cirrhosis.

76 survival and acute-on-chronic liver failure (ACLF) in patients awaiting LT, as well as early post-LT

77 velopment of acute-on-chronic liver failure (ACLF) in patients with liver cirrhosis is associated wit

78 irrhosis and acute-on-chronic liver failure (ACLF) include susceptibility to infection, immuneparesis

79 Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by mu

80 Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis.

81 Acute-on-chronic liver failure (ACLF) is a variably defined syndrome characterized by ac

82 Acute-on-chronic liver failure (ACLF) is an acute liver and multisystem failure in patie

83 Acute-on-chronic liver failure (ACLF) is an ailment with high incidence of multiorgan fa

84 Acute on chronic liver failure (ACLF) is associated with multisystem organ failure and p

85 Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation (AD) of c

86 Acute-on-chronic liver failure (ACLF) is characterized by systemic inflammation, monocyt

87 The term acute-on-chronic liver failure (ACLF) is intended to identify patients with chronic live

88 Although acute-on-chronic liver failure (ACLF) is the most severe clinical stage of cirrhosis, th

89 Acute on chronic liver failure (ACLF) results in extremely high short-term mortality in

90 The acute-on-chronic liver failure (ACLF) syndrome is characterized by acute decompensation

91 criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B vir

92 atients with acute-on-chronic liver failure (ACLF) with 3 or more failing organs (ACLF-3) is controve

93 presence of acute on chronic liver failure (ACLF) with three or more organs failing (ACLF-3) portend

94 ccurrence of acute-on-chronic liver failure (ACLF), a syndrome defined by an acute deterioration of l

95 of acute and acute-on-chronic liver failure (ACLF).

96 features of acute-on-chronic liver failure (ACLF).

97 irrhosis and acute on chronic liver failure (ACLF).

98 HBV) related acute-on-chronic liver failure (ACLF).

99 ered to have acute-on-chronic liver failure (ACLF).

100 a on PICD in acute-on-chronic liver failure (ACLF).

101 on (CHB) and acute-on-chronic liver failure (ACLF).

102 irrhosis and acute-on-chronic liver failure (ACLF).

103 , n = 52) or acute-on-chronic liver failure (ACLF, n = 57).

104 with grade-3 acute-on-chronic liver failure (ACLF-3).

105 sis, advanced liver fibrosis, heart failure, ACLF and death.

106 2%) in those with severe early course (final ACLF-2 or -3) independently of initial grades.

107 Eighty-one percent had their final ACLF grade at 1 week, resulting in accurate prediction o

108 First ACLF events were identified for each definition.

109 fatality rates decreased from 65% to 50% for ACLF and from 10% to 7% for cirrhosis.

110 nd 5-fold ($320 million to $1.7 billion) for ACLF.

111 and AD to establish diagnostic criteria for ACLF and showed that it is distinct from AD, based not o

112 We established diagnostic criteria for ACLF based on analyses of patients with organ failure (d

113 rent definitions and diagnostic criteria for ACLF have been proposed, and there is increasing recogni

114 e are no established diagnostic criteria for ACLF, so little is known about its development and progr

115 In 2011, the cost per hospitalization for ACLF was 3.5-fold higher than that for cirrhosis ($53,57

116 fair for Non-ACLF patients and moderate for ACLF patients.

117 clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Nat

118 les might identify patients at high risk for ACLF and death.

119 r ML-guided hypothesis generation in further ACLF research.

120 G1 ACLF events conferred a significantly increased risk of

121 Moreover, reversible decompensations for G1 ACLF have a lower risk of G3 ACLF, and liver-intrinsic O

122 Patients who recover from G1 ACLF have substantially increased risk of later developi

123 ACLF as compared to those who never have G1 ACLF.

124 f subsequent G3 ACLF relative no previous G1 ACLF (hazard ratio, 8.69; P < 0.001).

125 tly by type of OF characterizing previous G1 ACLF, with liver, coagulation, and circulatory failure p

126 Propensity matching for grade 1 (G1) ACLF, followed by Cox regression, was used to model risk

127 were significantly more likely to develop G3 ACLF relative to those with gastrointestinal bleed or in

128 tially increased risk of later developing G3 ACLF as compared to those who never have G1 ACLF.

129 Risk of G3 ACLF also varied significantly by type of OF characteriz

130 nsations for G1 ACLF have a lower risk of G3 ACLF, and liver-intrinsic OFs confer a much higher risk

131 ntrinsic OFs confer a much higher risk of G3 ACLF.

132 ignificantly increased risk of subsequent G3 ACLF relative no previous G1 ACLF (hazard ratio, 8.69; P

133 sed to model risk of subsequent grade 3 (G3) ACLF.

134 on for the Study of the Liver criteria grade ACLF severity from 1 (least severe) to 3 (most severe) b

135 LF in terms of risk of subsequent high-grade ACLF are unclear.

136 ver, the implications of surviving low-grade ACLF in terms of risk of subsequent high-grade ACLF are

137 significantly different between the groups (ACLF 28.77 vs. non-ACLF 21.23, P<0.0001).

138 Of the patients assessed, 303 had ACLF when the study began, 112 developed ACLF, and 928 d

139 received dual organs, 10 of them (29.4%) had ACLF.

140 undred fifty-seven patients in the study had ACLF and 175 patients had no ACLF (non-ACLF) pretranspla

141 sed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011

142 Among patients who had ACLF at enrollment, those with immune suppression and th

143 28-day mortality rate among patients who had ACLF when the study began was 33.9%, among those who dev

144 was 29.7%, and among those who did not have ACLF was 1.9%.

145 an, 112 developed ACLF, and 928 did not have ACLF.

146 8-1,066 registrants; P < 0.001), whereas HCV-ACLF declined by 45.2% (P < 0.001).

147 Hereto, ACLF-R cMons were characterized by transcripts associate

148 ysfunction (RD), hepatorenal syndrome (HRS), ACLF, and mortality.

149 I-ACLF was defined as >/= 2 organ failures given the signi

150 on-related acute-on-chronic liver failure (I-ACLF) derived from multicenter studies are required in o

151 decompensated infected cirrhosis patients, I-ACLF defined by the presence of two or more organ failur

152 nt predictors of poor 30-day survival were I-ACLF, second infections, and admission values of high ME

153 ion metabolic program as well as an impaired ACLF-R cMon functionality.

154 nd hepcidin levels were lower (P < 0.001) in ACLF patients with MOF than those without and other grou

155 nts, but were significantly more aberrant in ACLF patients.

156 Conclusion: AKI in ACLF carries a high mortality.

157 ormation about gut microbiome alterations in ACLF using quantitative metagenomics.

158 allel disease stages with maximal changes in ACLF.

159 of organ failure were predictors of death in ACLF.

160 olism and transport are severely deranged in ACLF patients and more so in those with MOF.

161 clusion: There is significant discordance in ACLF events by EASL and APASL criteria.

162 parameters in predicting bleeding events in ACLF group.

163 arallel with SI; it was remarkably higher in ACLF with kidney failure than in ACLF without kidney fai

164 ercentage Tf saturation (%SAT) was higher in ACLF-MOF (39.2%; P < 0.001) and correlated with poor out

165 is, increased in AD and further increased in ACLF, in parallel with SI; it was remarkably higher in A

166 transferrin (Tf) and ceruloplasmin levels in ACLF and ACLF-MOF, compared to patients with cirrhosis a

167 dicting futility (too sick to undergo LT) in ACLF is challenging.

168 in the subsets of circulating macrophages in ACLF-MOF, compared to other groups (P < 0.01).

169 Existing post-LT models in ACLF have been limited.

170 eases the incidence of PICD and mortality in ACLF patients.

171 F and can predict 15- or 30-day mortality in ACLF patients.

172 PICD is common and develops even with MVP in ACLF patients.

173 PICD is common and develops even with MVP in ACLF patients.

174 associated with recovery and nonrecovery in ACLF.

175 ficacy of terlipressin with noradrenaline in ACLF patients with HRS.

176 significant organ dysfunction that occurs in ACLF.

177 events occurred significantly more often in ACLF group with significantly reduced A10 and MCF.

178 st performance based on clinical outcomes in ACLF patients.

179 while significantly more ROTEM parameters in ACLF patients were affected.

180 T could be used for early prognostication in ACLF patients.

181 atic TLR4 expression was reduced by recAP in ACLF but not acute liver failure.

182 D163/MerTK expression levels were reduced in ACLF ex vivo following LPA, but not LPC, treatment.

183 tosis, and inflammation were up-regulated in ACLF patients, compared to patients with cirrhosis.

184 ATX up-regulation in ACLF promotes LPA production from LPC.

185 ystemic inflammation plays a primary role in ACLF progression.

186 han noradrenaline, with improved survival in ACLF patients with HRS-AKI.

187 y higher in ACLF with kidney failure than in ACLF without kidney failure in the absence of difference

188 The organ failure trends in ACLF showed an increasing proportion of cardiovascular a

189 er failure (ALF) and acute-on-chronic liver (ACLF) are distinct phenotypes of liver failure and, thus

190 lic fatty liver disease had among the lowest ACLF incidence rates but had the highest short-term mort

191 nd were injected with saline or LPS to mimic ACLF.

192 005 and 2017, waitlist registrants for NAFLD-ACLF rose by 331.6% from 134 to 574 candidates (P < 0.00

193 As of 2017, the NAFLD-ACLF population consisted primarily of persons aged 60 y

194 ntinues to grow and age, patients with NAFLD-ACLF will likely have the highest risk of waitlist morta

195 with compensated cirrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients du

196 tients with nonsevere early course (final no ACLF or ACLF-1) and high-to-very high (42%-92%) in those

197 n the study had ACLF and 175 patients had no ACLF (non-ACLF) pretransplant.

198 Non-ACLF patients analysed by ROTEM revealed parameters larg

199 y had ACLF and 175 patients had no ACLF (non-ACLF) pretransplant.

200 erence in mean eGFR between the ACLF and non-ACLF cohorts at 3 years posttransplant (56.35 mL/min vs.

201 in patients with stable liver cirrhosis (Non-ACLF) and in acute-on-chronic liver failure (ACLF) by CC

202 Fifty-five Non-ACLF patients and twenty-two patients with ACLF were ana

203 M analyses was determined to be fair for Non-ACLF patients and moderate for ACLF patients.

204 For assessing hemostasis in Non-ACLF and ACLF patients the underlying dataset shows adva

205 by CCT were outside the normal range in Non-ACLF and ACLF patients, but were significantly more aber

206 0-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%,

207 erent between the groups (ACLF 28.77 vs. non-ACLF 21.23, P<0.0001).

208 Assessment of ACLF patients at 3-7 days of the syndrome provides a too

209 ated; and (4) the strength of association of ACLF with SI was higher than with SCD.

210 Alcohol was the primary cause of ACLF in 88.1% of patients.

211 A common cause of ACLF is sepsis secondary to bacterial infection.

212 The course of SI and the course of ACLF (improvement, no change, or worsening) during hospi

213 We aimed to identify diagnostic criteria of ACLF and describe the development of this syndrome in Eu

214 rigin and lipid moieties with development of ACLF and death as an inpatient or within 30 days, after

215 ne independent predictors for development of ACLF were nosocomial infections, Model for Endstage Live

216 ch explains susceptibility to development of ACLF whereas acute liver failure is likely due to direct

217 olipids, were associated with development of ACLF, inpatient, and 30-day mortality and were also asso

218 flammatory process related to development of ACLF.

219 ese data support SI as the primary driver of ACLF in cirrhosis.

220 dy of 332 patients to evaluate the effect of ACLF, defined as an acute rise in the Model for End-Stag

221 (acute damage), supporting the hypothesis of ACLF.

222 The cumulative incidence of ACLF and mortality at 12 months were 50% and 34% in pati

223 nostic scores and probably the management of ACLF should base on similar principles.

224 demiology, economic burden, and mortality of ACLF in the United States.

225 Alb at admission predicted the occurrence of ACLF within 30 days and mortality at 90 days better than

226 , and may be involved in the pathogenesis of ACLF, clinical course, and mortality.

227 a and MELD-Na were independent predictors of ACLF in the WL, while CysC >= 1.5 mg/L, sarcopenia and a

228 The prevalence of ACLF among those hospitalizations increased from 1.5% (n

229 ial novel treatment option for prevention of ACLF but not acute liver failure.

230 liver disease and pose an additional risk of ACLF following infection.

231 severity of SI and frequency and severity of ACLF at enrollment were strongly associated.

232 les were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoho

233 ith nonsevere early course (final no ACLF or ACLF-1) and high-to-very high (42%-92%) in those with se

234 Patients without RD or ACLF at inclusion but with development of either had sig

235 ailure (ACLF) with 3 or more failing organs (ACLF-3) is controversial.

236 ium (MELD-Na) score, compared with the other ACLF groups; the proportion was greatest for patients wi

237 So far there are no biomarkers predicting ACLF.

238 774 patients with HBV related ACLF defined in the CANONIC study were analyzed accordin

239 was developed for patients with HBV related ACLF, allowing stratification into different clusters us

240 suggesting the need for more liver-specific ACLF criteria.

241 (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the S

242 Current study indicates that ACLF is a clinically and pathophysiology distinct even i

243 e was no difference in mean eGFR between the ACLF and non-ACLF cohorts at 3 years posttransplant (56.

244 matin binding was similarly increased in the ACLF group compared with control cirrhosis.

245 In the ACLF model, the severity of liver dysfunction and brain

246 sarcopenia are strongly associated with the ACLF and mortality in WL.

247 Therefore, ACLF patients were additionally subgrouped by bleeding e

248 for end-stage liver disease (MELD) score vs ACLF category.

249 irrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients during the 28-day fol

250 ients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects.

251 e were factors independently associated with ACLF at enrollment.

252 1beta and IL-1ra) in strong association with ACLF.

253 Candidates with ACLF were identified based on the European Association f

254 leukocyte count, and mortality compared with ACLF in patients with a prior history of AD.

255 y low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001).

256 circulating immune cells from patients with ACLF and acute decompensated (AD) cirrhosis and healthy

257 and was particularly marked in patients with ACLF and persisted after adjustment for antibiotic thera

258 on survival of MARS therapy in patients with ACLF could not be demonstrated.

259 olled trial (RCT), consecutive patients with ACLF diagnosed with HRS acute kidney injury (AKI) were r

260 Seventy-six percent of the patients with ACLF had acute kidney injury as their reason for decompe

261 Patients with ACLF have increased numbers of immunoregulatory monocyte

262 is increasing recognition that patients with ACLF may face disadvantages in the current United States

263 Patients with ACLF showed significantly higher levels of these markers

264 ican and a lower percentage of patients with ACLF than patients without ACLF were European American o

265 f race, a higher percentage of patients with ACLF than patients without ACLF were Native American and

266 n-ACLF patients and twenty-two patients with ACLF were analysed in this prospective cohort study.

267 Patients with ACLF were identified based on the European Association f

268 In all, 189 patients with ACLF were randomized either to MARS (n=95) or to standar

269 Consecutive patients with ACLF were randomly assigned to groups given 5 mug/kg G-C

270 Patients with ACLF were younger and more frequently alcoholic, had mor

271 than doubles the percentage of patients with ACLF who survive for 2 months; it also significantly red

272 One hundred twenty patients with ACLF, 20 patients with compensated cirrhosis, and 20 hea

273 patients with AD, culminate in patients with ACLF, and may be involved in the pathogenesis of ACLF, c

274 cytokines by immune cells from patients with ACLF, and might be developed to increase the innate immu

275 on, livers, and lymph nodes of patients with ACLF, compared with patients with stable cirrhosis and c

276 ndscape of transplantation for patients with ACLF, strategies to optimize organ utility, and data opp

277 Conclusion: Patients with ACLF-3 at the time of listing have greater 14-day mortal

278 ategory and ACLF-3 showed that patients with ACLF-3 had greater risk of 14-day mortality than status-

279 MELD-Na category revealed that patients with ACLF-3 had significantly greater mortality (subhazard ra

280 So, certain patients with ACLF-3 have poor outcomes regardless of MELD-Na score.

281 we found high mortality among patients with ACLF-3 on the liver transplant waitlist, even among thos

282 Patients with ACLF-3 were more likely to die or be removed from the wa

283 Patients with ACLF-3 who underwent liver transplantation (LT) between

284 ion of transplant priority for patients with ACLF-3.

285 mal transplantation window for patients with ACLF-3.

286 after liver transplantation in patients with ACLF-3.

287 nts listed status 1a and 5,099 patients with ACLF-3.

288 etabolites were measured in 50 patients with ACLF.

289 but comparable to controls in patients with ACLF.

290 c information in HBV cirrhotic patients with ACLF.

291 ent predictors of mortality in patients with ACLF.

292 dence of PICD and mortality in patients with ACLF.

293 for patients listed status 1a and those with ACLF-3 at listing.

294 his study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cy

295 ), acute decompensation of cirrhosis without ACLF (n = 9), cirrhosis without decompensation (n = 17),

296 (compensated, acutely decompensated without ACLF, and ACLF).

297 of C-reactive protein than patients without ACLF (P < .001).

298 of patients with ACLF than patients without ACLF were European American or African American.

299 of patients with ACLF than patients without ACLF were Native American and a lower percentage of pati

300 r levels of these markers than those without ACLF; (2) different cytokine profiles were identified ac