19 research outputs found
Doença HepĂĄtica CrĂłnica Agudizada: RevisĂŁo da ExperiĂȘncia de um Centro PortuguĂȘs de Referenciação
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of a patient with cirrhosis, frequently associated with multi-organ failure and a high short-term mortality rate. We present a retrospective study that aims to characterize the presentation, evolution, and outcome of patients diagnosed with ACLF at our center over the last 3 years, with a comparative analysis between the group of patients that had ACLF precipitated by infectious insults of bacterial origin and the group of those with ACLF triggered by a nonbacterial infectious insult; the incidence of acute kidney injury and its impact on the prognosis of ACLF was also analyzed. Twenty-nine patients were enrolled, the majority of them being male (89.6%), and the mean age was 53 years. Fourteen patients (48.3%) developed ACLF due to a bacterial infectious event, and 9 of them died (64.2%, overall mortality rate 31%); however, no statistical significance was found (p < 0.7). Of the remaining 15 patients (51.7%) with noninfectious triggers, 11 died (73.3%, overall mortality rate 37.9%); again there was no statistical significance (p < 0.7). Twenty-four patients (83%) developed acute kidney injury (overall mortality rate 65.5%; p < 0.022) at the 28-day and 90-day follow-up. Twelve patients had acute kidney injury requiring renal replacement therapy (41.37%; overall mortality rate 37.9%; p < 0.043). Hepatic transplant was performed in 3 patients, with a 100% survival at the 28-day and 90-day follow-up (p < 0.023). Higher grades of ACLF were associated with increased mortality (p < 0.02; overall mortality 69%).
CONCLUSIONS:
ACLF is a heterogeneous syndrome with a variety of precipitant factors and different grades of extrahepatic involvement. Most cases will have some degree of renal dysfunction, with an increased risk of mortality. Hepatic transplant is an efficient form of therapy for this syndrome.info:eu-repo/semantics/publishedVersio
Adiponectin, leptin, and IGF-1 are useful diagnostic and stratification biomarkers of NAFLD
[EN] Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver
disease where liver biopsy remains the gold standard for diagnosis. Here we aimed
to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor
1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with
the metabolome.
Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured
by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and
healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD,
31 controls) and correlated with clinical data, histology, genetic parameters, and
serum metabolomics.
Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC
0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between
obese and non-obese healthy controls, suggesting that obesity is not a confounding
factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis
(NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p < 0.0001). For the validation
cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC
0.63; p < 0.05). Combining adiponectin with specific serum lipids improved the assay
performance (AUROC 0.80; p < 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p<0.05), but combination with international normalized
ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p < 0.01).
Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with
specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis.CR was funded by FEDER through the COMPETE program
and by national funds through Fundação para a CiĂȘncia
e a Tecnologia (PTDC/MED-FAR/29097/2017âLISBOA-01-
0145-FEDER-029097) and by European Horizon 2020 (H2020-
MSCA-RISE-2016-734719). This work was also supported by
Fundação para a CiĂȘncia e Tecnologia (PD/BD/135467/2017)
and Portuguese Association for the Study of Liver/MSD
2017. JB was funded by Spanish Carlos III Health Institute
(ISCIII) (PI15/01132, PI18/01075 and Miguel Servet Program
CON14/00129 and CPII19/00008), co-financed by Fondo
Europeo de Desarrollo Regional (FEDER), Instituto de Salud
Carlos III (CIBERehd, Spain), La Caixa Scientific Foundation
(HR17-00601), FundaciĂłn CientĂfica de la AsociaciĂłn Española
Contra el CĂĄncer, and European Horizon 2020 (ESCALON
project: H2020-SC1-BHC-2018-2020)
Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients. METHODS: Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi's classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses. RESULTS: Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001), progressive hepatic inflammation (pâ=â0.029) and fibrosis severity (pâ=â0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (pâ=â0.059), despite no association with insulin resistance. In turn, hepatic steatosis (pâ=â0.015) and inflammation (pâ=â0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (pâ=â0.047) whereas complex I (pâ=â0.040) and III (pâ=â0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (pâ=â0.049) and with a trend with fibrosis severity (pâ=â0.056). CONCLUSIONS: In morbid obese patients, presence of IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction does not appear to be a major driving force contributing to muscle fat accumulation, insulin resistance or liver disease. Importantly, insulin resistance in muscle might occur at a late point in the insulin signaling cascade and be associated with IMCL and NAFLD severity
Status of hepatic DNA methylome predetermines and modulates the severity of non-alcoholic fatty liver injury in mice
Different locations but common associations in subcortical hypodensities of presumed vascular origin: cross-sectional study on clinical and neurosonologic correlates
Muscle mitochondrial enzymatic activities according to hepatic fibrosis severity.
<p>Differences in mean mitochondrial enzymatic activities, citrate synthase (A), complex I (B), complex II (C), complex III (D) and complex IV (E) with fibrosis severity. Error bars: 95% CI. There was a trend to a progressive increase in complex I activity according to fibrosis stage.</p
Patients main features.
<p>NASHâ=ânon alcoholic steatohepatitis, BMIâ=âbody mass index, WTHâ=âwaist to hip, ASTâ=âaspartate aminotransferase, ALTâ=âalanine aminotransferase, Îł-GTâ=âÎł-glutamyl transpeptidase, ALPâ=âalkaline phosphatase, NASâ=âNAFLD activity score.</p><p>P*â=âsignificance level in the comparison between NASH and non NASH.</p
Muscle morphology in morbidly obese patients with NAFLD and lean controls.
<p>NASHâ=ânon alcoholic steatohepatitis, T1Fâ=âtype 1 fibers, Î coefficientâ=âvariability coefficient, T2Fâ=âtype 2 fibers, EMCLâ=âextramyocellular lipids, EMCLâ=âintramyocellular lipids, RRFâ=âragged red fibers presence, COXâ=âpresence of cytochrome oxidase negative fibers.</p><p>P*â=âsignificance level in the comparison between controls and obese patients;</p><p>P**â=âsignificance level in the comparison between NASH and non NASH.</p
Muscle mitochondrial enzymatic activities according to hepatic steatosis degree.
<p>Differences in mean mitochondrial enzymatic activities, citrate synthase (A), complex I (B), complex II (C), complex III (D) and complex IV (E) with steatosis severity. Error bars: 95% CI. Complex I activity progressively increased with hepatic steatosis severity.</p