S. Gitto, Nicolò Mannelli, A. Tassi, F. Gabrielli, F. Nascimbeni, P. Andreone
{"title":"Liver transplantation and nonalcoholic steatohepatitis: the state of the art","authors":"S. Gitto, Nicolò Mannelli, A. Tassi, F. Gabrielli, F. Nascimbeni, P. Andreone","doi":"10.20517/mtod.2022.04","DOIUrl":"https://doi.org/10.20517/mtod.2022.04","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) represents one of the most diffuse liver diseases worldwide. It is a condition ranging from liver steatosis to non-alcoholic steatohepatitis (NASH) and NASH-related cirrhosis. Recently, the term metabolic dysfunction-associated fatty liver disease has been proposed in place of NAFLD, accenting the metabolic and cardiovascular risks that accompany hepatic disease. In the last decades, NASH and NASH-related cirrhosis have been the fastest growing indications for liver transplantation (LT), and they will probably overcome the other indications in next future. After LT, recipients show an important increase in body weight due to a greater caloric intake, partially because of the metabolic influence of immunosuppressant drugs, favoring the development of diabetes mellitus, dyslipidemias, and arterial hypertension. These metabolic complications will, in turn, elevate cardiovascular risk in this population. In this review, we analyze the main metabolic challenges of both pre-and post-LT periods.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenhao Li, C. Ng, Jingxuan Quek, K. Chan, C. Tan, R. Zeng, J. Yong, H. Tay, D. Tan, W. Lim, Douglas Chee, Jinyang Ho, N. Chew, L. Mak, M. Siddiqui, A. Sanyal, W. Alazawi, Naim Alkouri, M. Muthiah, M. Noureddin
{"title":"The growing prevalence of nonalcoholic fatty liver disease (NAFLD), determined by fatty liver index, amongst young adults in the United States. A 20-year experience","authors":"Wenhao Li, C. Ng, Jingxuan Quek, K. Chan, C. Tan, R. Zeng, J. Yong, H. Tay, D. Tan, W. Lim, Douglas Chee, Jinyang Ho, N. Chew, L. Mak, M. Siddiqui, A. Sanyal, W. Alazawi, Naim Alkouri, M. Muthiah, M. Noureddin","doi":"10.20517/mtod.2022.24","DOIUrl":"https://doi.org/10.20517/mtod.2022.24","url":null,"abstract":"Aim: The Global burden of nonalcoholic fatty liver disease (NAFLD) has significantly increased recently, with its prevalence mirroring increasing obesity and diabetes. However, population-specific evidence for young adults remains limited. Herein, we provide a 20-year trend analysis of NAFLD in young adults and examine factors associated with NAFLD and major adverse cardiovascular events (MACE) prevalence. Methods: This study uses data from the United States National Health and Nutrition Examination Survey (NHANES) 1999-2018. Fatty liver was examined with the fatty liver index (FLI) and United States-FLI (US-FLI), and advanced fibrosis was examined with the fibrosis-4 index. Clustered multivariate logistic regression analysis on the year of study was applied to obtain odds ratios (OR) for the estimation of events. Results: 13.31% (95%CI: 12.71% to 13.94%) of young adults had NAFLD. The prevalence increased from 9.98% in 1999 to 19.49% in 2018, with a statistically significant trend (P < 0.001). 9.52% and 5.29% of patients have clinically significant and advanced fibrosis, respectively. In multivariate analysis, diabetes (3.48, 95%CI: 2.37 to 5.11), hypertension (2.03, 95%CI: 1.62 to 2.55), elevated body mass index (1.22, 95%CI: 1.20 to 1.23, P < 0.001) significantly increases odds of NAFLD. The largest increase in odds was related to obesity (OR: 21.61, 95%CI: 16.95 to 27.55, P < 0.001). Young adults with NAFLD had a borderline non-significant increase in the prevalence of MACE compared to individuals without NAFLD (OR: 1.603, 95%CI: 0.949 to 2.708, P = 0.078). Conclusion: The rising prevalence of NAFLD in young adults depicts the changing landscape of NAFLD and its association with a significant increase in MACE. The challenge of effective risk stratification and education of these individuals remains.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Screening for advanced liver fibrosis in overweight and obese patients with NAFLD","authors":"N. Stefan","doi":"10.20517/mtod.2022.29","DOIUrl":"https://doi.org/10.20517/mtod.2022.29","url":null,"abstract":"","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alejandro Villalón, L. Díaz, E. Fuentes-López, Javier Villalón, F. Villalon, Gustavo Ayares, B. Yañez, R. Candia, J. Arab, M. Arrese
{"title":"Colorectal adenomas and MAFLD: a cross-sectional study in a hispanic screening cohort","authors":"Alejandro Villalón, L. Díaz, E. Fuentes-López, Javier Villalón, F. Villalon, Gustavo Ayares, B. Yañez, R. Candia, J. Arab, M. Arrese","doi":"10.20517/mtod.2021.17","DOIUrl":"https://doi.org/10.20517/mtod.2021.17","url":null,"abstract":"Aims: Prior evidence demonstrates an association between non-alcoholic fatty liver disease (NAFLD) and colorectal adenomas (CRA) risk. However, information using the new definition of the disease [i.e., metabolic dysfunction-associated fatty liver disease (MAFLD)] is scarce. We aimed to assess the relationship between MAFLD and CRA risk. Methods: We conducted a cross-sectional study including patients from three university centers in Chile who underwent a colonoscopy for colorectal cancer screening and abdominal imaging study. We obtained sociodemographic and clinical data, and we performed univariate and multivariable regression analyses. Results: In total, 895 patients were included; 42% were male, the mean age was 59.9 ± 9.3 years, and 37.8% (338) had CRA. Patients harboring polyps were predominantly males (48.2% vs. 38.2%, P = 0.002), older (61.6 ± 8.7 years vs. 58.9 ± 9.5 years, P < 0.001), and exhibited a higher body weight than controls [75 (66-88) kg vs. 72 (63-82.3) kg, P = 0.002]. Fifty-six percent of patients showed hepatic steatosis in imaging studies and 54.4% met MAFLD diagnostic criteria. The adenoma detection rate was higher in the MAFLD group compared to controls (46.4% vs. 27.5%, P < 0.001). In the multivariable analysis, MAFLD was significantly associated with the presence of CRA (odds ratio = 2.32; 95%CI: 1.68-3.19, P < 0.0001). There were no statistically significant differences of histopathological characteristics of the adenomas according to the presence of MAFLD. Conclusion: The present study shows that, in Chilean Hispanic subjects, MAFLD is associated with an increased risk of CRA. This information may be useful to design specific screening colonoscopy recommendations in MAFLD patients.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From liver fat to full-blown metabolic disorder: the kidney as target organ","authors":"M. Petroni, G. Marchesini","doi":"10.20517/mtod.2022.17","DOIUrl":"https://doi.org/10.20517/mtod.2022.17","url":null,"abstract":"study of subjects classified as advanced fibrosis by biomarker [high nonalcoholic fibrosis score (NFD) vs. low NFD; HR, 1.59], as well as in two studies where liver biopsy was available (fibrosis ≥ F3 vs. fibrosis < F3; HR, 2.75 and 3.25, respectively). The authors concluded that an effect of disease severity is very likely, but data are needed to support this evidence.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amedeo Lonardo, Ashwani K Singal, Natalia Osna, Kusum K Kharbanda
{"title":"Effect of cofactors on NAFLD/NASH and MAFLD. A paradigm illustrating the pathomechanics of organ dysfunction.","authors":"Amedeo Lonardo, Ashwani K Singal, Natalia Osna, Kusum K Kharbanda","doi":"10.20517/mtod.2022.14","DOIUrl":"https://doi.org/10.20517/mtod.2022.14","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9453927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33459644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolism and cancer-select topics","authors":"F. Lonardo, Casem Ballouk","doi":"10.20517/mtod.2022.05","DOIUrl":"https://doi.org/10.20517/mtod.2022.05","url":null,"abstract":"Metabolism and cancer intersect in multiple ways. Cancer has unique metabolic properties, including an inordinate reliance on anaerobic glycolysis (the Warburg effect). From an evolutionary standpoint, increased cancer incidence is associated with increased metabolic rates across species. Epidemiological data prove that a group of overlapping metabolic alterations, including obesity, type II Diabetes Mellitus, non-alcoholic fatty liver disease, and metabolic syndrome, constitute predisposing risk factors for cancer development in multiple anatomical sites. The molecular pathways underpinning this association involve hyperinsulinemia, hyperglycemia, sex hormones, adipokines, chronic inflammation, oxidative stress, and altered immune response.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolism and Target Organ Damage","authors":"N. Fearon, D. Pournaras","doi":"10.20517/mtod","DOIUrl":"https://doi.org/10.20517/mtod","url":null,"abstract":"People with diabetes mellitus (DM) undergo more elective surgery than those without DM; however, up to half of the patients are undiagnosed when referred for surgery. This is an opportunity to intervene and instigate a management plan. Preoperative strategies may vary based on coexisting medical diseases such as obesity and the availability of resources with the aim of achieving glycaemic control while also treating coexisting conditions. In the context of obesity, there is substantial overlap in some of the treatment strategies. Guidelines, such as those from the UK Centre for Perioperative Medicine, suggest target glycated haemoglobin levels, preoperative fasting blood glucose levels, and when to defer an elective operation or instigate treatment to proceed if deemed safe. Preoperatively glycaemic control is often achieved pharmacologically, and newer agents, including glucagon-like peptide one receptor agonists (GLP1-RA) and sodium-glucose co-transporter 2 (SGLT2) inhibitors, are emphasised in the preoperative management of diabetes mellitus, particularly if obesity is also present. A very low-energy diet is an underutilised but well-evidenced method of achieving both glycaemic control and weight loss with a particularly dominant effect on liver fat which is helpful for people who are due to undergo abdominal surgery. Bariatric-metabolic procedures are of growing interest as bridging interventions to surgery and are more commonly used for obesity, but they also have a well-recognized impact on the improvement and remission of DM. This review gives an overview of the necessity of preoperative identification of DM and strategies for management. Intra-operative glycaemic control is also discussed, and the role of stress hyperglycaemia perioperatively.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chronic obstructive pulmonary disease (COPD) and metabolic fatty liver syndromes: a dangerous but neglected liaison","authors":"A. Lonardo, B. Beghé, L. Fabbri","doi":"10.20517/mtod.2022.06","DOIUrl":"https://doi.org/10.20517/mtod.2022.06","url":null,"abstract":"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.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Barchetta, C. Chiappetta, A. Biasio, F. A. Cimini, L. Bertoccini, S. Dule, D. Capoccia, C. Cristofano, G. Silecchia, F. Leonetti, M. Baroni, A. Lenzi, M. Cavallo
{"title":"Expression of TGR5 in adipose tissue in relation to metabolic impairment and adipose tissue dysfunction in human obesity","authors":"I. Barchetta, C. Chiappetta, A. Biasio, F. A. Cimini, L. Bertoccini, S. Dule, D. Capoccia, C. Cristofano, G. Silecchia, F. Leonetti, M. Baroni, A. Lenzi, M. Cavallo","doi":"10.20517/mtod.2021.04","DOIUrl":"https://doi.org/10.20517/mtod.2021.04","url":null,"abstract":"Aim: Takeda G-protein-coupled receptor 5 (TGR5) is a functional receptor which mediates a variety of metabolic and immune processes and is involved in the regulation of adipocyte pathophysiology. Data on TGR5 in human adipose tissue are very limited. Therefore, the aims of this study were to investigate TGR5 expression in visceral adipose tissue (VAT) and explore its association with signs of VAT dysfunction and overt metabolic disease in individuals with obesity. Methods: Fifty obese candidates to bariatric surgery were recruited at Sapienza University, Rome, Italy. The expression of TGR5 and markers of VAT dysfunction were assessed by rt-PCR in omental fragments obtained intraoperatively. Page 2 of Barchetta et al. Metab Target Organ Damage 2021;1:8 https://dx.doi.org/10.20517/mtod.2021.04 12 Results: Individuals with higher VAT TGR5 levels (high-TGR5) had greater fasting glucose (P = 0.027) and worse lipid profile (total-cholesterol, P = 0.014; LDL-cholesterol, P = 0.022) than those with lower TGR5 (low-TGR5) expression. High-TGR5 subjects showed significantly higher expression of markers of AT-specific inflammation and insulin resistance, such as tissue metallopeptidase inhibitor 1 (TIMP1; P = 0.011), poly[ADP-ribose]polymerase 1 (PARP1, P = 0.034), and WNT1-inducible-signaling pathway protein 1 (WISP1, P = 0.05), apoptosis (caspase 7, P = 0.031), and lipid trafficking (ANGPTL4, P < 0.001), compared to low-TGR5 patients. High VAT TGR5 expression predicted the presence of abnormal glucose metabolism with AUROC = 0.925 (95%CI: 0.827-1.00, P = 0.001) for the age-, sex-, and waist circumference-adjusted ROC curve. Conclusion: Our data show that increased VAT TGR5 is associated with VAT dysfunction and impaired lipid trafficking and predicts the presence of metabolic disorders in human obesity, overall adding novel insights to the understanding of TGR5-mediated pathways in the clinical setting.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43089050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}