1,721,105 research outputs found
Diagnosi e storia naturale della steatosi epatica non alcolica. Performance e limiti delle tecniche diagnostiche invasive e non invasive e risultati del follow-up a lungo termine delle cirrosi criptogenetiche.
No full textIntroduzione e Scopo Generale La steatoepatite nonalcolica(NASH) [parte dello spettro della steatosi epatica nonalcolica(NAFLD)] è una sfida clinica ed un precursore di molti casi di cirrosi criptogenetica(CC). Abbiamo valutato performance e limiti di tecniche diagnostiche invasive e non invasive di NAFLD e la storia naturale di CC.
LAVORO I-Scopo Valutare se categorie istologiche secondo algoritmo FLIP/score SAF identificano distinti profili clinici. Metodi 218 biopsie per NAFLD; NASH e malattia severa(MS) diagnosticate secondo classificazione FLIP/SAF. Risultati Obesità centrale, HOMA e ALT predicono indipendentemente NASH; obesità centrale, HOMA, TG, ALT e piastrine predicono indipendentemente MS. Conclusioni NASH e MS presentano un grado più avanzato di insulino-resistenza (IR), supportando la rilevanza clinica della classificazione istologica FLIP/SAF.
LAVORO II-Scopo Confrontare l’istologia della NAFLD tra 625 pazienti(pz) con obesità morbigena (Coorte Bariatrica:CB) e 369 pz sovrappeso/moderatamente obesi con sospetta NAFLD (Coorte Epatologica:CE). Metodi NASH e fibrosi avanzata(FA) diagnosticate secondo classificazione FLIP/SAF. Risultati Sia NASH che FA sono più frequenti in CE che in CB. L’associazione tra CE e FA è indipendente da età, sesso, BMI, profilo metabolico, HOMA e ALT. Al contrario, la prevalenza di NASH è simile appaiando le due coorti per sesso-età e CE non risulta indipendentemente associata a NASH. Conclusioni Pz di CE hanno una fibrosi più avanzata di pz di CB. Ciò non è attribuibile a differenze in prevalenza di NASH, età, sesso e profilo metabolico.
LAVORO III-Scopo Valutare se il profilo clinico-istologico dei pz con ALT normali(ALTN) di CB differisce da quello dei pz di CE. Metodi Biopsie epatiche valutate secondo classificazione FLIP/SAF. Risultati ALTN sono più frequenti in pz di CB. Pz con ALTN di CB hanno un miglior profilo metabolico e meno spesso NASH e FA rispetto a pz con ALT elevate di CB. In pz di CE ALTN non sono associate alla severità metabolica/istologica. Conclusioni ALTN in pz di CB sono associate a un profilo istologico/metabolico meno severo, suggerendo una diversa patogenesi.
LAVORO IV-Scopo Validazione di 5 biomarcatori di steatosi in pz sottoposti a biopsia epatica per sospetta NAFLD. Metodi Severità della steatosi valutata istologicamente. Risultati Tutti i biormarcatori correlano con IR e diagnosticano accuratamente la steatosi. Tuttavia, la loro abilità di quantificare la steatosi è limitata, e fibrosi ed infiammazione hanno un effetto confondente. Conclusioni I biomarcatori diagnosticano la steatosi, ma non sono in grado di quantificarla e mancano di specificità.
LAVORO V-Scopo Valutare l’affidabilità dell’elastometria transitoria(ET) nel monitoraggio della fibrosi epatica. Metodi Analisi retrospettiva di 531 coppie di ET effettuate al basale e al follow-up a distanza di >1 giorno e <1 anno in 432 pz stabili, non trattati, con NAFLD/epatopatie croniche. Risultati Esiste una significativa variabilità nelle misurazioni a breve termine mediante ET correlata sia all’operatore sia al pz e non dovuta a progressione della fibrosi. Conclusioni ET non è uno strumento sufficientemente affidabile per il follow-up della fibrosi nei pz epatopatici.
LAVORO VI-Scopo Valutare caratteristiche cliniche, storia naturale e predittori di outcome nella CC. Metodi 91 pz con CC seguiti per 26.5 mesi. Risultati Patologie metaboliche e cardiovascolari, neoplasie extraepatiche, scompenso epatico, mortalità epato-correlata e carcinoma epatocelullare sono molto frequenti. Complicanze e morte epato-correlate sono predette da età e funzione epato-renale. Conclusioni CC può derivare da NASH occulta, ha una severa prognosi epato-correlata ed è associata ad eventi cardiovascolari e neoplasie suggerendo la necessità di sorveglianza.
Conclusioni Generali Abbiamo fornito nuovi dati che potranno essere di aiuto nella diagnosi e nel follow-up di pz con NAFLD.Background and General Aim-Nonalcoholic steatohepatitis(NASH) [part of nonalcoholic fatty liver disease(NAFLD) spectrum] is a clinical challenge and a precursor of most cryptogenic cirrhosis(CC) cases. We evaluated invasive and non-invasive diagnostic techniques in NAFLD and characterized CC course.
PAPER I-Aim:To assess if FLIP/SAF histological categories identify distinct patient profiles. Method:218 biopsy-proven NAFLD patients were selected; NASH was diagnosed according to FLIP algorithm and histologically severe disease(HSD) according to SAF score. Results:Central obesity, HOMA and ALT independently predicted NASH; central obesity, HOMA, TG, ALT and platelets independently predicted HSD. Conclusions:NASH and HSD patients show a more advanced obesity-related IR and worse liver tests supporting the clinical importance of FLIP/SAF histological classification.
PAPER II-Aim:To compare NAFLD histology between 625 morbidly obese patients undergoing bariatric surgery (Bariatric-cohort:BC) and 369 overweight/moderately obese patients referred for NAFLD (Hepato-cohort:HC). Method:NASH and advanced fibrosis(AF) diagnosed according to FLIP algorithm and SAF score. Results:Both AF and NASH were more prevalent in HC than in BC. The association between HC and AF was independent of age, sex, BMI, metabolic traits, HOMA and ALT. In contrast, NASH prevalence was similar in the matched cohorts and HC was not independently associated to NASH. Conclusions:HC patients have a more fibrosing disease than BC, which is not attributable to differences in NASH prevalence, age, sex and metabolic traits.
PAPER III-Aim:To assess if the clinico-histological profile of normal ALT(NALT) BC cases differs from HC cases. Method:Liver biopsies evaluated according to FLIP algorithm and SAF score. Results:NALT was more common in BC patients. NALT BC patients had a better metabolic profile and had less often NASH and AF than high ALT BC patients. In HC patients NALT was not associated with metabolic or histological severity. Conclusions:NALT in BC cases is associated with milder histology and metabolic derangements than HC cases, suggesting a different pathogenesis.
PAPER IV-Aim:To validate steatosis biomarkers in patients biopsied for suspected NAFLD. Method:The histological severity of steatosis was categorized and 5 biomarkers were tested. Results:All biomarkers were correlated with IR and accurately detected steatosis but their ability to quantify it was poor. Fibrosis and necroinflammation significantly confounded the biomarkers-steatosis association. Conclusions:Biomarkers detect steatosis, but they do not quantify it and lack of specificity.
PAPER V-Aim:To assess the reliability of transient elastometry(TE) in monitoring liver fibrosis changes during follow-up. Method:Retrospective analysis of 531, paired, baseline and follow-up liver stiffness measurements by TE >1day and <1year apart in 432 untreated/stable patients with NAFLD/other chronic liver diseases(CLD) was performed. Results:A substantial operator- and patient-related variability of repeated, short-term TE measurements, was observed, unrelated to true disease progression. Conclusions:TE alone may not be sufficient for a reliable follow-up of fibrosis in CLD patients.
PAPER VI-Aim:To evaluate CC clinical features, long-term course and predictors of outcome. Method:91 CC patients were followed-up for 26.5 months. Results:metabolic traits, cardiovascular diseases and extrahepatic malignancies were highly prevalent. Liver decompensation, liver-related death and HCC were common. Liver-related complications and death were predicted by age and hepato-renal function. Conclusions:CC may result from occult NASH, has a poor liver-related prognosis and is associated with cardiovascular events and cancer suggesting that surveillance programs are necessary.
Overall Conclusions-We have provided novel insights into diagnosis and natural history of NAFLD patients
Non-alcoholic fatty liver disease: Diagnosis and investigation
No full textGiven the worldwide increase in obesity and diabetes, non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is associated with increased hepatic and extrahepatic morbidity and mortality, mainly related to non-alcoholic steatohepatitis with fibrosis. An early diagnosis in the high-risk population with features of insulin resistance and a proper identification of those patients with progressive liver disease are needed. Practicing physicians dealing with NAFLD should be aware of and should carefully evaluate the extended spectrum of NAFLD-related extrahepatic diseases, which significantly affects liver- and non-liver-related prognosis. This clinical practice-oriented article reviews the diagnostic methods and staging strategies for NAFLD and proposes an investigational algorithm for a global evaluation of NAFLD patients. © 2014 S. Karger AG, Basel
Telomere shortening: An innocent bystander at the crossroad of NASH with ageing and cardiometabolic risk?
No full textEditorial of
"Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease-related advanced fibrosis.
Energy balance, glucose and lipid metabolism, cardiovascular risk and liver disease burden in adult patients with type 1 Gaucher disease
No full textGaucher disease (GD), the most prevalent lysosomal storage disease, is characterized by systemic accumulation of macrophages engorged with glycosphingolipid-laden lysosomes. Even though both lysosomes and sphingolipids play a pivotal role in metabolic homeostasis, little is known on metabolic abnormalities associated with GD. In this review, we discuss the peculiarity of energy balance and glucose and lipid metabolism in adult type 1 GD patients. Moreover, we evaluate the potential relationship between these metabolic derangements, cardiovascular risk and chronic liver disease. The limited data available show that adult type 1 GD is characterized by a hypermetabolic state, peripheral insulin resistance and hypolipidemia with markedly reduced HDL-cholesterol levels, partially reverted by enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Although this unfavorable metabolic profile has not been associated with increased incidence of type 2 diabetes and premature atherosclerosis, a natural history study has shown that cardio-cerebrovascular events and malignancy are the leading causes of death in treated type 1 GD patients. Hepatomegaly is frequently observed in GD and ERT/SRT are highly effective in reducing liver volume. Nevertheless, patients with GD may be at increased risk of long-term liver complications including cirrhosis and hepatocellular carcinoma. The role that ERT/SRT and/or lifestyle habits may have on such metabolic features of GD patients, and subsequently on long-term prognosis, deserves further investigations. To gain more insights into the peculiarity of GD metabolism may serve both surveillance and treatment purposes by helping to identify new markers of disease severity and define an updated natural history of GD
Is it time to include non-alcoholic fatty liver disease in the current risk scores for atrial fibrillation?
No full textno abstract availabl
Identifying lipid patterns through lipidomic profiling for MASLD detection and severity stratification
No full textThe increasing global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) has placed this condition at the forefront of chronic liver diseases, especially in Western populations. Strongly associated with metabolic comorbidities such as obesity, dyslipidemia, insulin resistance, and type 2 diabetes [1], MASLD follows a continuum that ranges from asymptomatic hepatic steatosis to the more advanced metabolic dysfunction-associated steatohepatitis (MASH). This progression, characterized by hepatocellular injury and inflammation, significantly increases the risk of fibrosis, cirrhosis, and hepatocellular carcinoma [2]. Although current non-invasive tools including imaging and serum-based biomarkers are helpful in initial evaluations, their limited sensitivity and specificity reduce their effectiveness in accurately staging the disease or predicting its progression [3]. To address this gap, we applied lipidomic profiling to investigate the molecular features associated with MASLD severity.
In this pilot study, we conducted untargeted lipidomic analyses on serum and plasma samples from a metabolically defined patient cohort spanning the full MASLD spectrum, including cases with advanced MASH. Lipids were extracted using a biphasic methyl-tert-butyl ether (MTBE) protocol [4] and analyzed by UHPLC coupled with high-resolution Orbitrap mass spectrometry. Lipid species were annotated using Compound Discoverer software and structurally validated through MS/MS fragmentation.
Our analysis revealed distinct lipidomic profiles corresponding to different stages of MASLD. Key changes were observed in ceramides, sphingolipids and phospholipids, with specific patterns reflecting the extent of steatosis and inflammatory activity. These results point to a gradual reprogramming of lipid metabolism as the disease progresses, highlighting lipidomic alterations as potential indicators of disease status.
Overall, our findings underscore the value of lipidomics as a high-resolution molecular tool for improving early detection, patient stratification, and personalized monitoring in MASLD. While larger validation studies are needed, this approach may enrich current diagnostic frameworks and support the transition toward a more personalized model of care
Role of ultrasound in the diagnosis and treatment of nonalcoholic fatty liver disease and its complications
No full textWe review the role of liver ultrasonography (US) and related techniques as non-invasive tools in predicting metabolic derangements, liver histology, portal hypertension and cardiovascular risk as well as allowing early diagnosis and management of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease. In this setting, US detects fatty changes as low as ≥20% and hepatic steatosis identified ultrasonographically, in its turn, closely mirrors coronary and carotid atherosclerosis burden. Semi-quantitative US indices (to exclude nonalcoholic steatohepatitis) and sonoelastography (to quantify fibrosis) help in predicting liver histology and selecting patients to submit to liver biopsy. Surveillance for hepatocellular carcinoma conducted through biannual US is mandatory and US has a role in guiding locoregional treatment and in evaluating the efficacy of treatment. High-intensity focused ultrasound can be delivered with precision resulting in coagulative necrosis of hepatocellular carcinoma without puncturing the liver. Costs and inconveniences have so far hampered its diffusion
Extra-hepatic manifestations and complications of nonalcoholic fatty liver disease
No full textThis review article aims to synthesize the evidence regarding nonalcoholic fatty liver disease (NAFLD) as a systemic disorder. We critically discuss the metabolic syndrome and its components; the cardiovascular and the endocrine system; chronic respiratory disorders; the musculoskeletal system; the skin; and extrahepatic tumors. We conclude that, while some of these extra-hepatic conditions clearly predispose to the development of secondary forms of NAFLD (typically hypothyroidism-induced NAFLD), others result from pre-existent NAFLD (e.g., certain extra-hepatic tumors) and others (such as Type 2 Diabetes) have, with NAFLD, mutual and bidirectional associations. Analyzed data imply that NAFLD is not merely a hepatic disease. It is also and possibly more importantly, a systemic disorder requiring a special awareness, a multidisciplinary approach and a multidimensional vision
The genetic basis of Insulin resistance. A brief review
No full textInsulin resistance, represents the primary physiologic defect underlying the metabolic syndrome (MS) which includes insulin resistance/hyperinsulinemia, glucose intolerance and/or type 2 diabetes mellitus, visceral obesity, hypertension, and dyslipidemia. This constellation of traits is a major risk factor of cardiovascular mortality and morbidity. Insulin sensitivity varies among individuals. Although environment, physical inactivity and caloric excess, plays an important role in the development of obesity and thus insulin resistance, several studies show that there are also a genetic influence in the development of insulin resistance. Extreme forms of insulin resistance may be caused by mutations in the genes for the insulin receptor and peroxisome proliferator-activated receptor gamma, these forms rare. The genetic basis for common more moderate forms of insulin resistance is likely to be polygenic and heterogeneous. There is evidence that gene variants may have phenotypic influences on more than one MS traits which may explain, in part, the clustering of these traits. We briefly review in this article the evidence that insulin resistance has a genetic basis. The identification of specific gene variants will help understanding the molecular basis of MS and ultimately will help to set up preventive and therapeutic interventio
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