125 research outputs found

    Principles of risk stratification in nonalcoholic fatty liver disease. A narrative review emphasizing non-invasive strategies

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    Nonalcoholic fatty liver disease (NAFLD) is an umbrella definition that describes the ectopic deposition of fat within the liver that occurs in the absence of inciting factors other than the metabolic syndrome and its individual features. NAFLD has a multi-factorial pathogenesis which determines heterogeneous clinical phenotypes and variable natural course spanning from liver-related (steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma) to extrahepatic outcomes (cardio-metabolic and cancer). This narrative review article leverages the key aspects of disease natural history as the background information to discuss studies that may inform strategies to risk-stratify NAFLD patients. Evaluation of hepatic fibrosis with non-invasive tools, including blood-based biomarkers and imaging-based elastometry techniques, seemingly retains the core information useful to predict the heterogeneous outcomes listed above. Additionally, genetic testing and metabolomic profiles may also be utilized to this end. In conclusion, a comprehensive understanding of the variable hepatic, cardio-metabolic and cancer outcomes of NAFLD may enable physicians and researchers to risk-stratify and accurately identify the multilayered prognosis of NAFLD individuals while also defining homogeneous patient subsets to enroll in clinical trials

    Shutting those revolving doors

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    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

    Extra-hepatic cancers in metabolic fatty liver syndromes

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    Non-alcoholic fatty liver disease and risk of incident chronic kidney disease: an updated meta-analysis

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    Objective: Studies reported a significant association between non-alcoholic fatty liver disease (NAFLD) and increased risk of chronic kidney disease (CKD). However, whether this risk changes with increasing severity of NAFLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of incident CKD. Design: We systematically searched PubMed, Web of Science and Scopus from January 2000 to August 2020 using predefined keywords to identify observational studies with a follow-up duration of ≥1 year, in which NAFLD was diagnosed by blood biomarkers/scores, International Classification of Diseases codes, imaging techniques or biopsy. Data from selected studies were extracted, and meta-analysis was performed using random-effects modelling. Results: 13 studies with 1 222 032 individuals (28.1% with NAFLD) and 33 840 cases of incident CKD stage ≥3 (defined as estimated glomerular filtration rate <60 mL/min/1.73 m2, with or without accompanying overt proteinuria) over a median follow-up of 9.7 years were included. NAFLD was associated with a moderately increased risk of incident CKD (n=10 studies; random-effects HR 1.43, 95% CI 1.33 to 1.54; I 2 =60.7%). All risks were independent of age, sex, obesity, hypertension, diabetes and other conventional CKD risk factors. Sensitivity analyses did not alter these findings. Funnel plot did not reveal any significant publication bias. Conclusion: This large and updated meta-analysis indicates that NAFLD is significantly associated with a~1.45-fold increased long-term risk of incident CKD stage ≥3. Further studies are needed to examine the association between the severity of NAFLD and risk of incident CKD

    Chronic obstructive pulmonary disease (COPD) and metabolic fatty liver syndromes: a dangerous but neglected liaison

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    This perspective article aims at addressing the potential commonalities associated with chronic obstructive pulmonary disease (COPD) and the two metabolic fatty liver syndromes: nonalcoholic fatty liver disease (NAFLD) and metabolic (associated) fatty liver disease (MAFLD). To this end, we briefly review the definitions and burdens of COPD and NAFLD and highlight the differences in the diagnostic criteria of NAFLD and MAFLD. We also critically discuss the recent line of research trying to identify an association between COPD and NAFLD. Moreover, among the chief co-morbidities of COPD patients, we identify significant six that exert a major impact on the natural course of COPD: major cardiovascular events, cardiac arrhythmias, metabolic syndrome, obstructive sleep apnea, osteoporosis, and psychodepression. The potential role of NAFLD in each of these COPD co-morbidities is accurately examined based on published studies. We conclude that both COPD and NAFLD/MAFLD are heterogeneous systemic syndromes. While the complex mechanistic links underlying the association of NAFLD/MAFLD with COPD and its co-morbidities remain to be fully elucidated, we highlight that the diagnosis of metabolic fatty liver syndromes in patients with COPD might be clinically relevant, as it might allow identifying a subset of COPD individuals who, being at risk of severe clinical outcomes, would need more comprehensive treatment approaches

    Concise review: gamma-glutamyl transferase - evolution from an indiscriminate liver test to a biomarker of cardiometabolic risk

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    This concise review article critically examines the recent medical literature regarding gamma glutamyl transferase (GGT) with a special emphasis on newly proposed indications for GGT use, including cardiovascular risk assessment.GGT is a ubiquitous glycosylated protein embedded in the outer surface of cell membranes, which catalyzes the transfer of glutamyl groups from various substrates and plays a key role in the antioxidant/pro-oxidant balance. In the past, the enzyme was considered a non-specific liver test. Current evidence supports the role of GGT in the assessment of portal hypertension in cystic fibrosis, porto-sinusoidal vascular disease, malignant mesothelioma, and incident type 2 diabetes and as a biomarker of cardiometabolic risk and cardiovascular disease.Several specific points including the use of GGT in hepatology as a sensitive but poorly specific test and the association of GGT with metabolic syndrome, nonalcoholic fatty liver disease and its fibrotic stages, cardiometabolic risk, chronic kidney disease, neurodegenerative disorders and dementia, idiopathic pulmonary arterial hypertension, and Corona Virus Disease 2019 (COVID-19) are addressed based on the most recent research in these fields. Putative mechanisms linking GGT with increased metabolic stress and the effects of various therapeutic interventions on GGT values are also discussed. We conclude that GGT has evolved from an indiscriminate liver test and an index of alcohol consumption to a biomarker of cardiometabolic health. The proper interpretation of GGT values (i.e., of hepatic vs. extrahepatic origin) is deeply affected by the clinical and epidemiological context. We propose that GGT may be utilized in public health campaigns, in the research arena, and in clinical practice to identify those individuals who can benefit most from the proactive preventive and therapeutic approaches, given that they are at high cardiometabolic risk

    Diabetes Affects Antibody Response to SARS-CoV-2 Vaccination in Older Residents of Long-term Care Facilities: Data From the GeroCovid Vax Study

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    Objective: Type 2 diabetes may affect the humoral immune response after vaccination, but data concerning coronavirus disease 19 (COVID-19) vaccines are scarce. We evaluated the impact of diabetes on antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in older residents of long-term care facilities (LTCFs) and tested for differences according to antidiabetic treatment. Research design and methods: For this analysis, 555 older residents of LTCFs participating in the GeroCovid Vax study were included. SARS-CoV-2 trimeric S immunoglobulin G (anti-S IgG) concentrations using chemiluminescent assays were tested before the first dose and after 2 and 6 months. The impact of diabetes on anti-S IgG levels was evaluated using linear mixed models, which included the interaction between time and presence of diabetes. A second model also considered diabetes treatment: no insulin therapy (including dietary only or use of oral antidiabetic agents) and insulin therapy (alone or in combination with oral antidiabetic agents). Results: The mean age of the sample was 82.1 years, 68.1% were women, and 25.2% had diabetes. In linear mixed models, presence of diabetes was associated with lower anti-S IgG levels at 2 (β = -0.20; 95% CI -0.34, -0.06) and 6 months (β = -0.22; 95% CI -0.37, -0.07) after the first vaccine dose. Compared with those without diabetes, residents with diabetes not using insulin had lower IgG levels at 2- and 6-month assessments (β = -0.24; 95% CI -0.43, -0.05 and β = -0.30; 95% CI -0.50, -0.10, respectively), whereas no differences were observed for those using insulin. Conclusions: Older residents of LTCFs with diabetes tended to have weaker antibody response to COVID-19 vaccination. Insulin treatment might buffer this effect and establish humoral immunity similar to that in individuals without diabetes

    Metabolic mechanisms for and treatment of NAFLD or NASH occurring after liver transplantation

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    This Review outlines the occurrence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) in patients who have undergone liver transplantation for prior NASH-related cirrhosis (recurrent) or other liver indications (de novo).The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major health concern worldwide. NAFLD - specifically its more advanced form, non-alcoholic steatohepatitis (NASH)-related cirrhosis - is now the fastest growing indication for liver transplantation in the USA and Europe. Although the short-term and mid-term overall survival rates of patients who receive a liver transplant for NASH-related cirrhosis are essentially similar to those of patients who receive a transplant for other liver indications, recipients with NASH-related cirrhosis have an increased risk of waiting-list mortality and of developing recurrent liver disease and cardiometabolic complications in the longer term after liver transplantation. This Review provides a brief overview of the epidemiology of NAFLD and NASH and the occurrence of NAFLD or NASH in patients after liver transplantation for NASH and other liver indications. It also discusses the putative metabolic mechanisms underlying the emergence of NAFLD or NASH after liver transplantation as well as optimal therapeutic approaches for recipients of liver transplants, including the management of cardiometabolic comorbidities, tailored immunosuppression, lifestyle changes and pharmacotherapy for NAFLD

    Effect of cofactors on NAFLD/NASH and MAFLD. A paradigm illustrating the pathomechanics of organ dysfunction

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    Primary nonalcoholic fatty liver disease (NAFLD) is bi-directionally associated with the metabolic syndrome and its constitutive features (“factors”: impaired glucose disposal, visceral obesity, arterial hypertension, and dyslipidemia). Secondary NAFLD occurs due to endocrinologic disturbances or other cofactors. This nosography tends to be outdated by the novel definition of metabolic associated fatty liver disease (MAFLD). Irrespective of nomenclature, this condition exhibits a remarkable pathogenic heterogeneity with unpredictable clinical outcomes which are heavily influenced by liver histology changes. Genetics and epigenetics, lifestyle habits [including diet and physical (in)activity] and immunity/infection appear to be major cofactors that modulate NAFLD/MAFLD outcomes, including organ dysfunction owing to liver cirrhosis and hepatocellular carcinoma, type 2 diabetes, chronic kidney disease, heart failure, and sarcopenia. The identification of cofactors for organ dysfunction that may help understand disease heterogeneity and reliably support inherently personalized medicine approaches is a research priority, thus paving the way for innovative treatment strategies
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