73 research outputs found

    Liver fibrosis in nonalcoholic fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality

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    Liver fibrosis is critical for liver-related outcomes and mortality in chronic liver disease, irrespective of etiology, including nonalcoholic fatty liver disease (NAFLD). NAFLD has been viewed as an independent correlate of cardiovascular risk. This review article briefly describes the cellular and molecular pathomechanisms underlying hepatic fibrosis. We then address noninvasive assessment of liver fibrosis. Finally, we discuss published evidence supporting fibrosis biomarkers’ role in assessing cardiovascular risk among patients with NAFLD. While histological assessment is the diagnostic standard of hepatic fibrosis, we specifically address noninvasive techniques, including equations based on anthropometric parameters, laboratory indices, and elastometry obtained with imaging techniques. The former group includes AST: ALT ratio, the Forns Index, the AST-to-platelet ratio index score, BARD (BMI, AAR, Diabetes) score, the fibrosis-4 index (FIB-4), the NAFLD fibrosis score, the gamma-glutamyl transferase-to-platelet ratio, and the Hepamet fibrosis score. The latter comprises elastographic techniques associated with ultrasonography or magnetic resonance. Our literature review identified numerous studies demonstrating that biomarkers of fibrosis (the most common being FIB-4) and elastographic techniques predict overall mortality and major cardiovascular events among NAFLD patients. The mechanisms accounting for this association are briefly reviewed. In addition to assessing hepatic fibrosis at baseline, during follow-up, and after therapeutic interventions in NAFLD patients, noninvasive assessment of hepatic fibrosis may predict cardiovascular events and overall mortality in these patients

    First Human Case of Tick-Borne Encephalitis in Non-Endemic Region in Italy: A Case Report

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    Tick-borne encephalitis (TBE), a human viral infectious disease caused by the tick-borne encephalitis virus (TBEV), is emerging in Italy, especially in the north-eastern area. No human cases of autochthonous TBE have been reported in Italy’s central regions (such as Emilia-Romagna, Italy). However, here we describe the first human case of TBEV infection in this region, pointing to endemic transmission of TBEV, supporting the concept of circulation of TBEV and of the presence of a possible hot spot in the Serramazzoni region in the Emilian Apennines

    The Fatty liver Index (FLI) 15 years later: a reappraisal

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    The Fatty Liver Index (FLI) is a non-invasive biomarker proposed, in 2006, by Bedogni’s group, to aid in identifying patients with suspected nonalcoholic fatty liver disease (NAFLD) to be submitted to liver ultrasonography to confirm steatosis. Criteria of Assessment of Narrative Review Articles, a scale for the assessment of quality of narrative review articles, inspired our review article, which aims at evaluating the scope of published articles on FLI issued over the last 15-year period. The analysis of retrieved data identified the following conclusions. First, given that FLI and NAFLD share the same risk factors, FLI can be used to identify NAFLD among populations at risk to be submitted to screening. Second, FLI is able to identify the hazard of atherosclerosis, both at a subclinical stage and as an overt disease. Third, FLI detects incident diabetes and chronic kidney disease. However, evidence supporting the notion that FLI also predicts the metabolic syndrome, some endocrine disorders, certain tumor types, and overall and cause-specific mortality appears to be more limited. In conclusion, 15 years after its first publication, FLI has been validated as a robust biomarker of both steatosis and NAFLD. Moreover, the scope of FLI has been expanded to previously unexpected areas. Finally, we discuss FLI limitations and a research agenda aimed at further improving the accuracy of FLI scores in predicting liver-related outcomes, endocrine-metabolic disorders, cancer risk, and survival

    Diagnostic accuracy of ultrasonography for the detection of hepatic steatosis: an updated meta-analysis of observational studies

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    Aim: we examined the diagnostic accuracy of ultrasonography to detect any HS (defined as steatotic hepatocytes ‚Č• 5% on histology) and moderate-severe HS (defined as steatotic hepatocytes ‚Č• 30% on histology) by performing a systematic review and meta-analysis.Methods: we systematically searched PubMed, Web of Science, and Scopus databases, from January 2011 to February 2021, to identify studies conducted in adults investigating the diagnostic accuracy of ultrasonography vs. histology for detecting either ‚Č• 5% histologically defined HS or moderate-severe HS (‚Č• 30%). Meta-analysis was performed using random-effects modeling.Results: twelve studies were included involving a total of 2921 individuals, 1710 (58.5%) of whom had HS ‚Č• 5% by histology. The overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ultrasonography for the detection of ‚Č• 5% histologically defined HS, compared to histology, were 82% (95% confidence interval 76%-86%), 80% (72%-86%), 4.0 (2.90-5.70), and 0.23 (0.18-0.30), respectively. Based on the pooled analysis of seven studies, the overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ultrasonography for the detection of ‚Č• 30% histologically defined HS were 85% (72%-92%), 85% (73%-93%), 5.72 (3.06-10.7), and 0.18 (0.10-0.33) , respectively. Funnel plots did not reveal any significant publication bias.Conclusion: conventional ultrasonography allows for reliable and accurate detection of ‚Č• 5% histologically defined HS compared to histology. These findings call for an extensive use of conventional ultrasonography in the clinical arena.<br/

    Liver Fibrosis Biomarkers Accurately Exclude Advanced Fibrosis and Are Associated with Higher Cardiovascular Risk Scores in Patients with NAFLD or Viral Chronic Liver Disease

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    Liver fibrosis predicts liver-related and cardiovascular outcomes in chronic liver disease patients. We compared the diagnostic performance of various liver fibrosis biomarkers for identifying histological significant/advanced fibrosis. Additionally, the correlations of such liver fibrosis biomarkers with cardiovascular risk (CVR) scores were evaluated. 173 patients with viral hepatitis (157 HCV and 16 HBV) and 107 with a non-alcoholic fatty liver disease (NAFLD) were consecutively enrolled. Various liver fibrosis biomarkers: aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (ARR), AST to Platelet Ratio Index (APRI), Fibrosis-4 (FiB-4), Forns index, NAFLD fibrosis score (NFS), BARD (body mass index (BMI), AAR, Diabetes) score, and Hepamet fibrosis score (HFS), were used to identify significant/advanced fibrosis. CVR was assessed by using the SCORE, the Progetto CUORE, or the Framingham risk scoring systems. Liver fibrosis biomarkers performed better in predicting advanced rather than significant liver fibrosis in all patients, regardless of chronic liver disease aetiology. Forns index and HFS performed best in predicting advanced fibrosis in patients with viral chronic liver disease and NAFLD. Lower cut-offs of these liver fibrosis biomarkers had high negative predictive values for advanced fibrosis overall, as well as in patients with NAFLD or viral chronic liver disease. FIB-4, Forns index, NFS, and HFS were positively correlated with SCORE and Framingham risk scores. In conclusion, liver fibrosis biomarkers accurately exclude advanced fibrosis and positively correlate with CVR scores in patients with chronic liver disease

    Sex disparity in hepatocellular carcinoma owing to NAFLD and non-NAFLD etiology: epidemiological findings and pathobiological mechanisms

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    Nonalcoholic fatty liver disease (NAFLD) exhibits sexual dimorphism, with men being more exposed than women to the risk of simple steatosis, nonalcoholic steatohepatitis fibrosis, and hepatocellular carcinoma (HCC), while the protection conferred to women seemingly disappears with aging and reproductive senescence (i.e., menopause). HCC, the most common primary liver cancer, which carries an ominous prognosis, may result from various genetic and non-genetic risk factors. NAFLD is now projected to become the most common cause of HCC. HCC also exhibits a definite sexual dimorphism in as much as it has a worldwide high male-to-female ratio. In this review article, we focus on sex differences in the epidemiological features of HCC. Moreover, we discuss sex differences in the clinical outcome and molecular pathobiology of NAFLD-HCC. By highlighting the research gaps to be filled, the aim of this review is to prompt future research of sex differences in HCC and facilitate developing personalized cancer prevention strategies, detection, and treatments to achieve better patient outcomes in NAFLD-HCC, considering sex differences in HCC pathobiology

    Sex Differences in NAFLD: State of the Art and Identification of Research Gaps

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    In spite of tremendous research advancements in nonalcoholic fatty liver disease (NAFLD), our understanding of sex-differences in NAFLD remains insufficient. This review summarizes current knowledge on sex differences in NAFLD, identifies current gaps, and discusses important considerations for future research. The prevalence and severity of NAFLD are higher in men than in women during the reproductive age. However, after menopause, NAFLD occurs at a higher rate in women suggesting that estrogen is protective. Sex differences also exist for the major risk factors of NAFLD. In general, animal models of NAFLD recapitulate sex differences observed in patients with more severe steatosis and steatohepatitis, more pro-inflammatory/pro-fibrotic cytokines, and a higher incidence of hepatic tumors in males than females. Based on computer modeling, female and male livers are metabolically distinct with unique regulators modulating sex-specific metabolic outcomes. Analysis of the literature reveals that most published clinical and epidemiological studies fail to examine sex differences appropriately. Considering the paucity of data on sex differences and the knowledge that regulators of pathways relevant to current therapeutic targets for NAFLD differ by sex, clinical trials should be designed to test drug efficacy and safety according to sex, age, reproductive stage (i.e., menopause) and synthetic hormone use. CONCLUSION: Sex differences do exist in the prevalence, risk factors, fibrosis, and clinical outcomes of NAFLD suggesting that, while not yet incorporated, sex will probably be considered in future practice guidelines. Adequate consideration of sex differences, sex hormones/menopause status, age, and other reproductive information in clinical investigation and gene association studies of NAFLD are needed to fill current gaps and implement precision medicine for patients with NAFLD. This article is protected by copyright. All rights reserved

    A round trip from nonalcoholic fatty liver disease to diabetes: molecular targets to the rescue?

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    Evidence suggests a close relationship between nonalcoholic fatty liver disease (NAFLD) and type two diabetes (T2D). On the grounds of prevalence of disease, both conditions account for a significant financial cost for health care systems and individuals. Aim of this review article is to explore the epidemiological basis and the putative molecular mechanisms underlying the association of NAFLD with T2D. Epidemiological studies have shown that NAFLD is associated to the development of incident T2D and either reversal or improvement of NAFLD will result into decreased risk of developing incident T2D. On the other side of the coin data have shown that T2D will worsen the course of NAFLD doubling the risk of disease progression (i.e. evolution from simple steatosis to advanced fibrosis, cirrhosis, hepatocellular carcinoma, liver transplant and death). Conversely, NAFLD will contribute to metabolic decompensation of T2D. The pathogenesis of T2D in NAFLD patients may be mediated by several hepatokines impairing metabolic control. Among these, Fetuin-B, which causes glucose intolerance and is increased in patients with T2D and NAFLD with fibrosis is one of the most promising. T2D may affect the progression of NAFLD by acting at different levels of the pathogenic cascade involving gut microbiota and expanded, inflamed, dysfunctional adipose tissue. In conclusion, T2D and NAFLD are mutually, closely and bi-directionally associated. An improved understanding of molecular pathogenesis underlying this bi-directional association may allow us to be able to prevent the development of T2D by halting the progression of NAFLD

    Extra-hepatic manifestations and complications of nonalcoholic fatty liver disease

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    This 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

    Pathogenesis of hypothyroidism-induced NAFLD: Evidence for a distinct disease entity?

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    Nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, may be associated with primary hypothyroidism. However, the pathogenesis underlying such an association is complex and not completely understood. Here, we specifically discuss the pathogenic mechanisms potentially involved in hypothyroidism-induced NAFLD. To this end, we summarize the general pathophysiology of thyroid hormones (TH). Next, we analyze the published data from rodent studies by discussing whether hypothyroid rats may develop NAFLD via hyperphagia; whether mitochondria become energetically more efficient; what the overall energy balance is and if diversion of fatty substrates occurs; and the latest advancements in molecular pathogenesis brought about by metabolomics, cell imaging, lipophagy, autophagy and genetically engineered mouse models. Moreover, we discuss the data published regarding humans on the pathogenic role of TH, metabolic syndrome and other risk factors in hypothyroidism-related NAFLD as well as the putative mechanisms underlying the development of NAFLD-related hepatocellular carcinoma in hypothyroidism. In conclusion, although many research questions still remain unanswered, the pathophysiology of hypothyroidism-induced NAFLD makes this a potentially curable and distinct disease entity. However, further studies are needed to better elucidate the underlying mechanisms, and to ascertain whether treatment with either TH or thyromimetic agents improves NAFLD
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