ライフサイエンスコーパス: NASH

1 NASH affects an estimated 3% to 6% of the US population

2 NASH and AF were associated with a greater risk of outco

3 NASH biopsies showed a higher CD61(+) platelets, and mos

4 NASH is a serious condition that can progress to cirrhos

5 NASH is strongly associated with obesity, dyslipidemia,

6 NASH patients ages 65-69 had an increased risk of waitli

7 NASH patients had higher serum LPS and hepatocytes LPS l

8 NASH resolution with no worsening of fibrosis was observ

9 NASH resolved in all mice receiving saroglitazar.

10 NASH was significantly associated with increased risk of

11 NASH-induced changes in Kupffer cell enhancers were driv

12 0.89 (95% CI, 0.82-0.95), borderline zone 1 NASH with AUROC of 0.91 (95% CI, 0.83-0.99), and fibrosi

13 had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty

14 ology primary outcome, (2) borderline zone 1 NASH, and (3) fibrosis.

15 For borderline zone 1 NASH, the model (P = 0.0004) retained baseline and chang

16 rline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver but not NASH.

17 Recent trials addressing NASH treatment in PLWH are discussed.

18 patient-reported outcomes (PROs) in advanced NASH.

19 Patients with advanced NASH (NASH Clinical Research Network stage F3 or F4) wer

20 A total of 2154 patients with advanced NASH were included: 52.5% with F4 NASH, 40% male, 72% wi

21 clinical and PROs in patients with advanced NASH.

22 es mellitus frequently present with advanced NASH.

23 Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mice represent a mod

24 tients with NASH will develop cirrhosis, and NASH is predicted to become the leading indication for l

25 e) at 5 years and regression of fibrosis and NASH at 1 and 5 years.

26 tologic measures of fibrosis improvement and NASH resolution.

27 collagen deposition in GAN DIO-NASH mice and NASH patient samples.

28 entify who is at risk of fibrosis, NAFLD and NASH among PLWH, and explore the diagnostic accuracy of

29 plays a role in the development of NAFLD and NASH by activating ACC.

30 ring systems exist to characterize NAFLD and NASH, liver biopsy is the only accepted method for diagn

31 ion between human immunodeficiency virus and NASH, and the issues related to the inclusion of PLWH in

32 al characterization, to define "NoNASH" and "NASH" patients.

33 histologic NAS score, 48% were classified as NASH by SAF score.

34 ow the progression of liver diseases such as NASH.

35 Associations between NASH-fibrosis variants and metabolites were assessed usi

36 the children with fatty liver or borderline NASH developed definite NASH.

37 Out of the patients with borderline NASH in the histologic NAS score, 48% were classified as

38 ase activity score >= 4), fibrosis (F1-F3 by NASH Clinical Research Network criteria), and elevated l

39 Activity Score >=4, stage 2 or 3 fibrosis by NASH Clinical Research Network classification, and absol

40 llected and the following scores calculated: NASH clinical scoring system (NCS), aspartate aminotrans

41 ary center cohort, patients with concomitant NASH and CHB had more AF and shorter time to development

42 en validated as molecular targets to counter NASH.

43 or overlap between published "omics"-defined NASH signatures.

44 differentiate between not NASH and definite NASH with a sensitivity of 74% and specificity of 67% (A

45 nt differences between not NASH and definite NASH.

46 liver or borderline NASH developed definite NASH.

47 enrollment, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline

48 s associated with a reduced risk of definite NASH (ADH1B*2: OR, 0.80; P < .01 vs ADH1B*1: OR, 0.96; P

49 of 1.6 +/- 0.4 years, borderline or definite NASH resolved in 29% of the children, whereas 18% of the

50 categorized as no-NASH or probable/definite NASH based on standardized histological assessment.

51 Any progression to definite NASH and/or in fibrosis was associated with adolescent a

52 lammation and collagen deposition in GAN DIO-NASH mice and NASH patient samples.

53 with the clinical features of NASH, GAN DIO-NASH mice demonstrated key components of the metabolic s

54 Liver lesions in GAN DIO-NASH mice showed similar morphological characteristics c

55 logical and transcriptome changes in GAN DIO-NASH mouse and human NASH patients.

56 The GAN DIO-NASH mouse model demonstrates good clinical translatabil

57 highlighting the suitability of the GAN DIO-NASH mouse model for identifying therapeutic targets and

58 osis but ameliorates oxidative stress-driven NASH, indicating that p38alpha plays distinct roles depe

59 Each NASH-fibrosis variant demonstrated a specific metabolite

60 ion of imaging parameters that predict early NASH and disease activity.

61 h advanced NASH were included: 52.5% with F4 NASH, 40% male, 72% with type 2 diabetes, baseline liver

62 se (DIO) mice represent a model of fibrosing NASH.

63 non-alcoholic steatohepatitis and fibrosis (NASH-fibrosis), including a recently identified variant

64 to care, but currently none are approved for NASH.

65 as a diagnostic pre-screening biomarker for NASH.

66 a promising alternative to liver biopsy for NASH diagnosis and monitoring.

67 he optimal mf3D-MRE technical parameters for NASH detection.

68 Obese adults at risk for NASH were enrolled between 2015 and 2017 (prospective co

69 ciated liver biopsies, the gold standard for NASH diagnosis, probably explains the poor overlap betwe

70 resent an effective therapeutic strategy for NASH treatment.

71 ior to biopsy to identify those suitable for NASH clinical trial enrolment.

72 re, we review the most promising targets for NASH treatment, along with the most advanced therapeutic

73 here are currently no approved therapies for NASH, the bile acid-derived FXR agonist obeticholic acid

74 and characterizing novel drug therapies for NASH.

75 Analyses of liver tissues from NASH patients reveal that YAP is increased in KCs and th

76 45, 81% women, and 81 [46%] with histologic NASH) were used for model derivation.

77 ameters that best correlated with histologic NASH, and MRI-PDFF to estimate steatosis.

78 Human NASH features hepatic neutrophil infiltration and up-reg

79 tome changes in GAN DIO-NASH mouse and human NASH patients.

80 and as markers of advanced fibrosis in human NASH.

81 The etiology of human NASH is multifactorial, and identifying reliable molecul

82 RF-calculated gene signatures identified NASH patients in independent cohorts with high accuracy.

83 Despite its importance, NASH is underrecognized in clinical practice.

84 4), bile duct ligation, and more importantly NASH.

85 h diet and exercise can dramatically improve NASH outcomes, significant lifestyle changes can be chal

86 ar, a PPAR alpha/gamma agonist would improve NASH in the diet-induced animal model of NAFLD.

87 It significantly improved NASH resolution (p < 0.001) and the SAF scores (p < 0.05

88 ox, inflammatory, and fibrogenic activity in NASH.

89 ment of the intestinal epithelial barrier in NASH.

90 and hedgehog; how clearance of dead cells in NASH via efferocytosis may affect inflammation and fibro

91 MPK-caspase-6 axis regulates liver damage in NASH, implicating AMPK and caspase-6 as therapeutic targ

92 r cells culminate in fibrosis development in NASH, focusing on triggers and consequences of hepatocyt

93 (a hallmark of NASH), is highly elevated in NASH patients but not in fatty livers in obese individua

94 of steatosis, inflammation, and fibrosis in NASH development.

95 er steatosis to inflammation and fibrosis in NASH.

96 he risk of hepatocellular carcinoma (HCC) in NASH patients with cirrhosis is not well quantified.

97 sitive (TLR4(+) ) macrophages were higher in NASH than simple steatosis or controls and correlated wi

98 KCs for regulation of liver inflammation in NASH.

99 in regulating steatosis and inflammation in NASH.

100 rogenic hepatocyte-macrophage-HSC network in NASH.

101 evaluate the impact of age on LT outcomes in NASH.

102 e issues related to the inclusion of PLWH in NASH clinical trials.

103 cipating in distinct biological processes in NASH as a function of sex.

104 ivated protein kinase (AMPK) is repressed in NASH.

105 ative to baseline and histologic response in NASH.

106 essed by MRI-PDFF and histologic response in NASH.

107 d to model complex liver diseases, including NASH.

108 sion of CXCL1 itself in the liver can induce NASH in HFD-fed mice and to test the therapeutic potenti

109 ury and fibrosis in the HFD(+Cxcl1) -induced NASH model that is associated with strong hepatic p38alp

110 dative burst, markedly reduced CXCL1-induced NASH and stress kinase activation in HFD-fed mice.

111 or methionine-choline deficient diet-induced NASH in mice.

112 tion, and fibrosis in a Western diet-induced NASH mouse model.

113 t l-amino acid-defined high-fat diet-induced NASH.

114 atitis (NASH), and in mice with diet-induced NASH.

115 tiple targets, ameliorated CXCL1/HFD-induced NASH or methionine-choline deficient diet-induced NASH i

116 ering caspase-6 activated in human and mouse NASH.

117 PK knockout aggravated liver damage in mouse NASH models.

118 lipid accumulation and fibrosis in multiple NASH mouse models.

119 obesity and its complications T2D and NAFLD/NASH.

120 n the impact of cellular senescence in NAFLD/NASH and discuss the effectiveness and safety of novel s

121 tty liver disease and steatohepatitis (NAFLD/NASH) and insulin resistance.

122 Patients with advanced NASH (NASH Clinical Research Network stage F3 or F4) were enro

123 e therapeutic potential of IL-22 in this new NASH model.

124 Currently, no NASH-specific therapies are approved by the US Food and

125 re were 1,089 CHB patients, classified as no-NASH (n = 904, 83%) or NASH (n = 185, 17%), with 52 (6%)

126 Patients were categorized as no-NASH or probable/definite NASH based on standardized his

127 hase 2 trial, 140 patients with noncirrhotic NASH, diagnosed by magnetic resonance imaging-proton den

128 APRI was able to differentiate between not NASH and definite NASH with a sensitivity of 74% and spe

129 o showed significant differences between not NASH and definite NASH.

130 zone 3 NASH, and 21% had fatty liver but not NASH.

131 -9.0], P < 0.01) when compared to absence of NASH and AF (reference).

132 ion therapies addressing multiple aspects of NASH pathogenesis are expected to provide benefit for pa

133 ivation might ameliorate multiple aspects of NASH.

134 The association of NASH with obesity, type 2 diabetes mellitus, and dyslipi

135 fat fraction (MRI-PDFF) in the detection of NASH in individuals undergoing bariatric surgery.

136 Of the three histological determinants of NASH, ballooning and inflammation, but not steatosis, we

137 All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between Jan

138 is the only accepted method for diagnosis of NASH.

139 To end the epidemic of NASH and prevent its complications, including cirrhosis

140 tological and pathophysiological features of NASH along with improvement in ALT and dyslipidemia in t

141 NGM282 improved the histological features of NASH in 12 weeks with significant reductions in NAS and

142 Consistent with the clinical features of NASH, GAN DIO-NASH mice demonstrated key components of t

143 e for neutrophil infiltration (a hallmark of NASH), is highly elevated in NASH patients but not in fa

144 In an in vivo model of NASH, 10b decreased liver triglyceride levels and showed

145 assess treatment response in a rat model of NASH.

146 then combined to derive predictive models of NASH and disease activity by nonalcoholic fatty liver di

147 emphasized the sexually dimorphic nature of NASH and its link with fibrosis, calling for the integra

148 aspase-6 inhibition, even after the onset of NASH, improved liver damage and fibrosis.

149 in E treatment improves clinical outcomes of NASH patients with bridging fibrosis or cirrhosis.

150 However, the pathogenesis of NASH is still unclear.

151 ived oxidative stress in the pathogenesis of NASH.

152 Persistence of NASH was associated with no decrease in fibrosis and les

153 ikely that patients develop the phenotype of NASH by multiple mechanisms, and thus the optimal treatm

154 slipidemia has led to an emerging picture of NASH as the liver manifestation of metabolic syndrome.

155 ith clinical outcomes (P < 0.05) in place of NASH.

156 en serostatus, and diabetes, the presence of NASH and concomitant advanced fibrosis (AF) was signific

157 iver injury and prevented the progression of NASH, including steatosis, inflammation, and fibrosis in

158 and exposure to TCS with the progression of NASH.

159 ntial role of newer NCS in the regulation of NASH, however, remain unknown.

160 bariatric surgery, we observed resolution of NASH in liver samples from 84% of patients 5 years later

161 Resolution of NASH was observed at 1 year after bariatric surgery in b

162 The primary endpoint was the resolution of NASH without worsening of fibrosis at 5 years.

163 +/- 7.4 kg/m(2); P = .017 with resolution of NASH).

164 The primary endpoint was resolution of NASH.

165 ADH1B*2 reduces the risk of NASH and fibrosis in adults with NAFLD regardless of alc

166 and Curcuminoids can reduce the severity of NASH by reducing steatosis, fibrosis, oxidative stress,

167 uminoids) in a Stelic animal model (STAM) of NASH.

168 ently in phase 3 trials for the treatment of NASH, are reviewed.

169 As potential treatment of NASH, mitochondrial uncouplers show promise for future d

170 couplers have potential for the treatment of NASH.

171 as a therapeutic target for the treatment of NASH.

172 lic formulation (BPF99) for the treatment of NASH.

173 chanisms, and thus the optimal treatments of NASH will likely evolve to personalized therapy once we

174 understand the mechanistic underpinnings of NASH in each patient.

175 improvement (>=1 stage) with no worsening of NASH was achieved in 38% of patients receiving aldafermi

176 her, our results indicate that, depending on NASH stage, hepatic Shp plays an opposing role in steato

177 CS including Rebaudioside A and sucralose on NASH using high fat diet induced obesity mouse model by

178 isk of outcomes compared to AF (P = 0.01) or NASH alone (P < 0.01).

179 nts, classified as no-NASH (n = 904, 83%) or NASH (n = 185, 17%), with 52 (6%) versus 27 (15%) experi

180 ly among patients with alcohol-associated or NASH-related cirrhosis and those not followed in subspec

181 +/- 4.1 kg/m(2) in patients with persistent NASH vs reduction of 13.4 +/- 7.4 kg/m(2); P = .017 with

182 o a logistic regression model that predicted NASH with cross-validated area under the receiver operat

183 d and thirty-six patients with biopsy-proven NASH and bridging fibrosis or cirrhosis seen at Indiana

184 aims were to determine whether biopsy-proven NASH impacts clinical outcomes in CHB patients and asses

185 Key inclusion criteria were biopsy-proven NASH with Nonalcoholic Fatty Liver Disease Activity Scor

186 0 severely obese patients with biopsy-proven NASH, defined by the NASH clinical research network hist

187 Form-36, Chronic Liver Disease Questionnaire-NASH, EuroQol-5D, and Work Productivity and Activity Imp

188 , the limited availability of representative NASH cohorts with associated liver biopsies, the gold st

189 ively our results showed that BPF99 resolves NASH and ameliorates key histological and pathophysiolog

190 WD-fed knockout mice developed severe NASH, which was associated with increased BA concentrati

191 abetes (T2D), non-alcoholic steatohepatitis (NASH) and a host of other comorbidities including cardio

192 patients with non-alcoholic steatohepatitis (NASH) and significant liver fibrosis.

193 progresses to non-alcoholic steatohepatitis (NASH) and subsequent cirrhosis.

194 mal models of non-alcoholic steatohepatitis (NASH) are important tools in preclinical research and dr

195 reatments for non-alcoholic steatohepatitis (NASH) are still unsatisfactory.

196 nced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors,

197 Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver

198 Non-alcoholic steatohepatitis (NASH) is major health burden lacking effective pharmacol

199 ding NAFL and non-alcoholic steatohepatitis (NASH) were analyzed.

200 a target for non-alcoholic steatohepatitis (NASH), an advanced phase of NAFLD.

201 diet-induced non-alcoholic steatohepatitis (NASH).

202 opsy-confirmed nonalcoholic steatohepatitis (NASH) (nonalcoholic fatty liver disease activity score >

203 ssociated with nonalcoholic steatohepatitis (NASH) and contribute to toxin-induced liver fibrosis in

204 FLD, including nonalcoholic steatohepatitis (NASH) and hepatic fibrosis.

205 Patients with nonalcoholic steatohepatitis (NASH) are waitlisted at older ages than individuals with

206 progression to nonalcoholic steatohepatitis (NASH) as characterized by the additional emergence of in

207 derline zone 1 nonalcoholic steatohepatitis (NASH) at baseline, with resolution in 28% (12 of 46).

208 rd to diagnose nonalcoholic steatohepatitis (NASH) but is invasive with potential complications.

209 in adults with nonalcoholic steatohepatitis (NASH) but not diabetes, but its impact on long-term pati

210 als within the nonalcoholic steatohepatitis (NASH) clinical research network from 2005 through 2015.

211 nducted by the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network.

212 diagnose early nonalcoholic steatohepatitis (NASH) is a major unmet need.

213 Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disea

214 Nonalcoholic steatohepatitis (NASH) is considered as a pivotal stage in nonalcoholic f

215 Nonalcoholic steatohepatitis (NASH) is considered as severe hepatic manifestation of t

216 Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty

217 e treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multip

218 composition in nonalcoholic steatohepatitis (NASH) patients.

219 development of nonalcoholic steatohepatitis (NASH) represents another leading cause of liver-related

220 steatosis and nonalcoholic steatohepatitis (NASH), and (2) the effects of LPI and genetic disruption

221 liver) and 25 nonalcoholic steatohepatitis (NASH), and in mice with diet-induced NASH.

222 a hallmark of nonalcoholic steatohepatitis (NASH), but how this occurs during the progression from s

223 athogenesis of nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain poorly under

224 e steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer.

225 se (NAFLD) and nonalcoholic steatohepatitis (NASH), have steadily increased and now affect approximat

226 gressive form, nonalcoholic steatohepatitis (NASH), requires novel therapeutic approaches to prevent

227 progresses to nonalcoholic steatohepatitis (NASH), which increases the risk for the development of c

228 -associated or nonalcoholic steatohepatitis (NASH)-related cirrhosis.

229 patients with nonalcoholic steatohepatitis (NASH).

230 nderpinning of nonalcoholic steatohepatitis (NASH).

231 ential role in nonalcoholic steatohepatitis (NASH).

232 development of nonalcoholic steatohepatitis (NASH).

233 mprovements in nonalcoholic steatohepatitis (NASH).

234 patients with nonalcoholic steatohepatitis (NASH).

235 patients with nonalcoholic steatohepatitis (NASH).

236 opsy-confirmed nonalcoholic steatohepatitis (NASH).

237 evelopment for nonalcoholic steatohepatitis (NASH).

238 nd fibrosis in nonalcoholic steatohepatitis (NASH).

239 ients may have nonalcoholic steatohepatitis (NASH).

240 isk factor for nonalcoholic steatohepatitis (NASH).

241 e treatment of nonalcoholic steatohepatitis (NASH).

242 patients with nonalcoholic steatohepatitis (NASH).

243 improvement in nonalcoholic steatohepatitis (NASH).

244 patients with nonalcoholic steatohepatitis (NASH).

245 se (NAFLD) and nonalcoholic steatohepatitis (NASH).

246 al in treating nonalcoholic steatohepatitis (NASH).

247 or of death in nonalcoholic steatohepatitis (NASH).

248 Among patients with AF, superimposed NASH predicted poorer clinical outcomes.

249 The NASH diet induced significant changes in Kupffer cell en

250 Our results suggest a link between the NASH-protective variant in MTARC1 to the metabolism of s

251 ents with biopsy-proven NASH, defined by the NASH clinical research network histologic scores.

252 lecular patterns associated with each of the NASH-fibrosis variants under investigation.

253 tology and scored centrally according to the NASH Clinical Research Network criteria.

254 orphological characteristics compared to the NASH patient validation set, including macrosteatosis, l

255 recognized in aging; however, their link to NASH has not been explored.

256 nd fibrosis during the transition of NAFL to NASH and liver failure.

257 present, how simple steatosis progresses to NASH remains obscure and effective pharmacological thera

258 liver disease (NAFLD) and its progression to NASH are commonly accompanied by several pathophysiologi

259 y was to determine why mice are resistant to NASH development and the involvement of p38 mitogen-acti

260 as a major determinant of liver responses to NASH progression and responses to drugs.

261 urs during the progression from steatosis to NASH remains obscure.

262 ecifically in the transition of steatosis to NASH, mice were fed the HFCF diet for 4 weeks, followed

263 n of Cxcl1 and/or IL-8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing liver infla

264 of CXCL1 is sufficient to drive steatosis-to-NASH progression in HFD-fed mice through neutrophil-deri

265 ing system bears the risk of underdiagnosing NASH in comparison to SAF score.

266 The molecular mechanisms underlying NASH development remain obscure.

267 Among UNOS NASH registrants (N = 6,630), 58% had diabetes.

268 ransplant mortality in individuals >=65 with NASH, and cardiovascular disease was the leading cause o

269 From 2004 to 2017, 14 197 adults with NASH were waitlisted, and the proportion >=65 increased

270 ng database was used to identify adults with NASH, hepatitis C virus (HCV) infection, and alcohol-rel

271 ndividuals with risk alleles associated with NASH-fibrosis: rs738409C>G in PNPLA3, rs58542926C>T in T

272 roved metabolic derangements associated with NASH.

273 hree imaging parameters that correlated with NASH.

274 hear stiffness at 60 Hz best correlated with NASH.

275 The outcomes of individuals with NASH were similar to patients of the same age group with

276 In mice with NASH, LPS serum levels and LPS hepatocyte localization w

277 ted in lower liver inflammation in mice with NASH.

278 improved clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis.

279 In patients with NASH and diabetes or insulin resistance, low AGER1 level

280 ase 2 human clinical trials in patients with NASH and diabetic nephropathy.

281 med a double-blind study of 78 patients with NASH at 9 centers in the United States.

282 Among 354 Mayo Clinic patients with NASH cirrhosis, 253 (71%) had diabetes and 145 (41%) wer

283 th an increased risk of HCC in patients with NASH cirrhosis.

284 The mortality rate among patients with NASH is substantially higher than the general population

285 In a long-term follow-up of patients with NASH who underwent bariatric surgery, we observed resolu

286 An estimated 20% of patients with NASH will develop cirrhosis, and NASH is predicted to be

287 In a phase 2 trial of patients with NASH, aldafermin reduced liver fat and produced a trend

288 n increased in livers of older patients with NASH, as assessed by real time quantitative PCR (RT-qPCR

289 Patients with NASH, cirrhosis, and portal hypertension (hepatic venous

290 In a phase 2b study of 162 patients with NASH, cirrhosis, and portal hypertension, 1 year of biwe

291 ty and efficacy of GR-MD-02 in patients with NASH, cirrhosis, and portal hypertension.

292 In patients with NASH, liver fibrosis is the main determinant of mortalit

293 were significantly reduced in patients with NASH-cirrhosis.

294 ffects of bariatric surgery in patients with NASH.

295 istry, and serum bile acids in patients with NASH.

296 of GPR55 were up-regulated in patients with NASH.

297 as also significantly lower in patients with NASH.

298 to those of liver tissues from patients with NASH.

299 prospective, phase 2 study in patients with NASH.

300 All adult liver transplant registrants with NASH between 2004 and 2017 were identified using the Uni