26,308 results on '"Fatty Liver"'
Search Results
2. Carnitine-acylcarnitine translocase deficiency: a case report with autopsy
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Chennakeshava Thunga, Suvradeep Mitra, Devi Dayal, and Sadhna Lal
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Autopsy ,Fatty liver ,Pathology ,Medicine ,Internal medicine ,RC31-1245 - Abstract
Fatty acid oxidation defects are a heterogeneous group of disorders related to the mitochondrial fatty acid oxidation pathway. Carnitine acylcarnitine translocase (CACT) is an enzyme responsible for the unidirectional transport of acylcarnitine across the inner mitochondrial membrane. This enzyme plays a crucial role in the oxidation of fatty acids. The autopsy pathology of the CACT deficiency is described in only a few cases. We describe the autopsy pathology of a child with CACT deficiency dominantly in the form of microvesicular steatosis of the hepatocytes, renal proximal tubular epithelia, cardiac myocytes, and rhabdomyocytes. The diagnosis was further confirmed on whole exome sequencing with compound heterozygous variants in the exon 1 (c.82G>T, p.Gly28Cys; likely pathogenic) and exon 5 (c.535G>A, p.Asp179Asn; uncertain significance) of the SLC25A20 gene. This case elucidates the histopathology of the liver and the detailed autopsy of a case of CACT deficiency from India.
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- 2024
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3. The GCKR-P446L gene variant predisposes to raised blood cholesterol and lower blood glucose in the P446L mouse-a model for GCKR rs1260326
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Brian E. Ford, Shruti S. Chachra, Katrina Rodgers, Tabassum Moonira, Ziad H. Al-Oanzi, Quentin M. Anstee, Helen L. Reeves, Jörn M. Schattenberg, Rebecca J. Fairclough, David M. Smith, Dina Tiniakos, and Loranne Agius
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Liver ,Glucose metabolism ,Glucokinase ,Type 2 diabetes ,Fatty liver ,Blood cholesterol ,Internal medicine ,RC31-1245 - Abstract
Objectives: The Glucokinase Regulatory Protein GKRP, encoded by GCKR, enables acute regulation of liver glucokinase to support metabolic demand. The common human GCKR rs1260326:Pro446 > Leu variant within a large linkage disequilibrium region associates with pleiotropic traits including lower Type 2 diabetes risk and raised blood triglycerides and cholesterol. Whether the GCKR-P446 > L substitution is causal to the raised lipids is unknown. We determined whether mouse GKRP phenocopies the human GKRP:P446 > L substitution and studied a GKRP:P446L knockin mouse to identify physiological consequences to P446 > L. Methods: GKRP-deficient hepatocytes were transfected with adenoviral vectors for human or mouse GKRP:446 P or 446 L for cellular comprehensive analysis including transcriptomics consequent to P446 > L. Physiological traits in the diet-challenged P446L mouse were compared with pleiotropic associations at the human rs1260326 locus. Transcriptomics was compared in P446L mouse liver with hepatocytes overexpressing glucokinase or GKRP:446 P/L. Results: 1. P446 > L substitution in mouse or human GKRP similarly compromises protein expressivity of GKRP:446 L, nuclear sequestration of glucokinase and counter-regulation of gene expression. 2. The P446L knockin mouse has lower liver glucokinase and GKRP protein similar to human liver homozygous for rs1260326-446 L. 3. The diet-challenged P446L mouse has lower blood glucose, raised blood cholesterol and altered hepatic cholesterol homeostasis consistent with relative glucokinase-to-GKRP excess, but not raised blood triglycerides. Conclusions: Mouse GKRP phenocopies the human GKRP:P446 > L substitution despite the higher affinity for glucokinase of human GKRP. The diet-challenged P446L mouse replicates several traits found in association with the rs1260326 locus on chromosome 2 including raised blood cholesterol, lower blood glucose and lower liver glucokinase and GKRP protein but not raised blood triglycerides.
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- 2023
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4. Methodological advancements in organ-specific ectopic lipid quantitative characterization: Effects of high fat diet on muscle and liver intracellular lipids
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Dogan Grepper, Cassandra Tabasso, Axel K.F. Aguettaz, Adrien Martinotti, Ammar Ebrahimi, Sylviane Lagarrigue, and Francesca Amati
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Lipid droplets ,Intrahepatic lipids ,Intramyocellular lipids ,Fatty liver ,Lipid metabolism ,Obesity ,Internal medicine ,RC31-1245 - Abstract
Objective: Ectopic lipid accumulation is a hallmark of metabolic diseases, linking obesity to non-alcoholic fatty liver disease, insulin resistance and diabetes. The use of zebrafish as a model of obesity and diabetes is raising due to the conserved properties of fat metabolism between humans and zebrafish, the homologous genes regulating lipid uptake and transport, the implementation of the ‘3R’s principle and their cost-effectiveness. To date, a method allowing the conservation of lipid droplets (LDs) and organs in zebrafish larvae to image ectopic lipids is not available. Our objectives were to develop a novel methodology to quantitatively evaluate organ-specific LDs, in skeletal muscle and liver, in response to a nutritional perturbation. Methods: We developed a novel embedding and cryosectioning protocol allowing the conservation of LDs and organs in zebrafish larvae. To establish the quantitative measures, we used a three-arm parallel nutritional intervention design. Zebrafish larvae were fed a control diet containing 14% of nutritional fat or two high fat diets (HFDs) containing 25 and 36% of dietary fats. In muscle and liver, LDs were characterized using immunofluorescence confocal microscopy. In liver, intrahepatocellular lipids were discriminated from intrasinusoid lipids. To complete liver characteristics, fibrosis was identified with Masson’s Trichrome staining. Finally, to confirm the conservation and effect of HFD, molecular players of fat metabolism were evaluated by RT-qPCR. Results: The cryosections obtained after setting up the embedding and cryopreservation method were of high quality, preserving tissue morphology and allowing the visualization of ectopic lipids. Both HFDs were obesogenic, without modifying larvae survival or development. Neutral lipid content increased with time and augmented dietary fat. Intramuscular LD volume density increased and was explained by an increase in LDs size but not in numbers. Intrahepatocellular LD volume density increased and was explained by an increased number of LDs, not by their increased size. Sinusoid area and lipid content were both increased. Hepatic fibrosis appeared with both HFDs. We observed alterations in the expression of genes associated with LD coating proteins, LD dynamics, lipogenesis, lipolysis and fatty acid oxidation. Conclusions: In this study, we propose a reproducible and fast method to image zebrafish larvae without losing LD quality and organ morphology. We demonstrate the impact of HFD on LD characteristics in liver and skeletal muscle accompanied by alterations of key players of fat metabolism. Our observations confirm the evolutionarily conserved mechanisms in lipid metabolism and reveal organ specific adaptations. The methodological advancements proposed in this work open the doors to study organelle adaptations in obesity and diabetes related research such as lipotoxicity, organelle contacts and specific lipid depositions.
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- 2023
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5. Peroxisomal regulation of energy homeostasis: Effect on obesity and related metabolic disorders
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Brian Kleiboeker and Irfan J. Lodhi
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Peroxisomes ,Diabetes ,Obesity ,Fatty liver ,Plasmalogen ,Lipid metabolism ,Internal medicine ,RC31-1245 - Abstract
Background: Peroxisomes are single membrane-bound organelles named for their role in hydrogen peroxide production and catabolism. However, their cellular functions extend well beyond reactive oxygen species (ROS) metabolism and include fatty acid oxidation of unique substrates that cannot be catabolized in mitochondria, and synthesis of ether lipids and bile acids. Metabolic functions of peroxisomes involve crosstalk with other organelles, including mitochondria, endoplasmic reticulum, lipid droplets and lysosomes. Emerging studies suggest that peroxisomes are important regulators of energy homeostasis and that disruption of peroxisomal functions influences the risk for obesity and the associated metabolic disorders, including type 2 diabetes and hepatic steatosis. Scope of review: Here, we focus on the role of peroxisomes in ether lipid synthesis, β-oxidation and ROS metabolism, given that these functions have been most widely studied and have physiologically relevant implications in systemic metabolism and obesity. Efforts are made to mechanistically link these cellular and systemic processes. Major conclusions: Circulating plasmalogens, a form of ether lipids, have been identified as inversely correlated biomarkers of obesity. Ether lipids influence metabolic homeostasis through multiple mechanisms, including regulation of mitochondrial morphology and respiration affecting brown fat-mediated thermogenesis, and through regulation of adipose tissue development. Peroxisomal β-oxidation also affects metabolic homeostasis through generation of signaling molecules, such as acetyl-CoA and ROS that inhibit hydrolysis of stored lipids, contributing to development of hepatic steatosis. Oxidative stress resulting from increased peroxisomal β-oxidation-generated ROS in the context of obesity mediates β-cell lipotoxicity. A better understanding of the roles peroxisomes play in regulating and responding to obesity and its complications will provide new opportunities for their treatment.
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- 2022
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6. Study Results from Department of Internal Medicine Provide New Insights into Non-Alcoholic Fatty Liver Disease (Increased Level of The Plasminogen Activator Inhibitor Type-1 is Associated with Severity of NAFLD).
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NON-alcoholic fatty liver disease ,FATTY liver ,PLASMINOGEN activator inhibitors ,INTERNAL medicine ,ZYMOGENS ,BLOOD coagulation factors - Abstract
A recent study conducted by the Department of Internal Medicine has found that Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease globally. The study focused on the relationship between NAFLD and Plasminogen Activator Inhibitor-1 (PAI-1), a protein associated with thrombosis and hypercoagulable state. The researchers discovered that there is an increase in PAI-1 levels in patients with NAFLD, and these levels have an independent effect on the degree of liver fibrosis. This study provides new insights into the severity of NAFLD and its associated risk factors. [Extracted from the article]
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- 2024
7. Study Results from University of Catania in the Area of Malnutrition Published (Malnutrition-Related Liver Steatosis, CONUT Score and Poor Clinical Outcomes in an Internal Medicine Department).
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INTERNAL medicine ,FATTY degeneration ,MALNUTRITION ,TREATMENT effectiveness ,FATTY liver - Abstract
A study conducted by researchers at the University of Catania in Italy explored the relationship between malnutrition-related liver steatosis and the CONUT score, a tool for assessing malnutrition. The study analyzed data from 247 patients hospitalized in an Internal Medicine department and found that severe steatosis was associated with higher in-hospital mortality and longer stays compared to mild steatosis. Additionally, the study identified a high CONUT score as an independent risk factor for sepsis. These findings suggest that the CONUT score can be a useful tool for assessing the nutritional status of hospitalized patients. [Extracted from the article]
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- 2024
8. Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice
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Joshua Stokar, Irina Gurt, Einav Cohen-Kfir, Oran Yakubovsky, Noa Hallak, Hadar Benyamini, Natan Lishinsky, Neta Offir, Joseph Tam, and Rivka Dresner-Pollak
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Menopause ,OVX ,Fatty Liver ,Transcriptome ,Estrogen ,Adropin ,Internal medicine ,RC31-1245 - Abstract
Objective: Menopause is associated with visceral adiposity, hepatic steatosis and increased risk for cardiovascular disease. As estrogen replacement therapy is not suitable for all postmenopausal women, a need for alternative therapeutics and biomarkers has emerged. Methods: 9-week-old C57BL/6 J female mice were subjected to ovariectomy (OVX) or SHAM surgery (n = 10 per group), fed a standard diet and sacrificed 6- & 12 weeks post-surgery. Results: Increased weight gain, hepatic triglyceride content and changes in hepatic gene expression of Cyp17a1, Rgs16, Fitm1 as well as Il18, Rares2, Retn, Rbp4 in mesenteric visceral adipose tissue (VAT) were observed in OVX vs. SHAM. Liver RNA-sequencing 6-weeks post-surgery revealed changes in genes and microRNAs involved in fat metabolism in OVX vs. SHAM mice. Energy Homeostasis Associated gene (Enho) coding for the hepatokine adropin was significantly reduced in OVX mice livers and strongly inversely correlated with weight gain (r = −0.7 p < 0.001) and liver triglyceride content (r = −0.4, p = 0.04), with a similar trend for serum adropin. In vitro, Enho expression was tripled by 17β-estradiol in BNL 1 ME liver cells with increased adropin in supernatant. Analysis of open-access datasets revealed increased hepatic Enho expression in estrogen treated OVX mice and estrogen dependent ERα binding to Enho. Treatment of 5-month-old OVX mice with Adropin (i.p. 450 nmol/kg/twice daily, n = 4,5 per group) for 6-weeks reversed adverse adipokine gene expression signature in VAT, with a trended increase in lean body mass and decreased liver TG content with upregulation of Rgs16. Conclusions: OVX is sufficient to induce deranged metabolism in adult female mice. Hepatic adropin is regulated by estrogen, negatively correlated with adverse OVX-induced metabolic phenotypes, which were partially reversed with adropin treatment. Adropin should be further explored as a potential therapeutic target and biomarker for menopause-related metabolic derangement.
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- 2022
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9. Value of screening for nonalcoholic fatty liver disease in hyperuricemic patients with normal body mass index by two-dimensional ultrasound: Upper Egypt experience
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Amro M Hassan, Mohammed H.A Elhaw, Ahmed Abd-Elrady Ahmed, Tarek M.M Mansour, Tarek M Abd-Elaziz, and Mohamed Z.A Shoaeir
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fatty liver ,hyperuricemia ,nonalcoholic fatty liver disease ,Internal medicine ,RC31-1245 - Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is major health problem, as it affects 20‑30% of the general population, and patients with NAFLD are at risk of progression toward liver cirrhosis and hepatocellular carcinoma and consequently lead to liver transplantation. NAFLD is strongly associated with obesity and metabolic syndrome, so NAFLD is usually seen in patients who have increased BMI, type 2 diabetes, and high cholesterol and triglycerides. Uric acid (UA) could play a role in pathogenesis of metabolic syndrome through oxidative stress and inflammatory response. Moreover, UA has been shown to promote lipid peroxidation, which could play a role in initiation and progression of NAFLD. Aim To evaluate the value of screening for NAFLD in hyperuricemic patients with normal BMI by two-dimensional ultrasound. Patients and methods This cross-section study was conducted on 100 persons: 50 patients diagnosed with hyperuricemia as the case group, and 50 persons with normal serum uric acid (SUA) who were crossed matched with the cases as a control group. Results This study showed that hyperuricemic patients had high rate of NAFLD (38%) more than people with normal SUA (20%), with P value was 0.025, and grade of NAFLD was higher in individuals with high SUA than individuals with normal SUA group, with P value was 0.048. Moreover, the levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were significantly increased in hyperuricemic patients more than individuals with normal UA level. Conclusions This study showed high rate of NAFLD among individuals with high SUA than individuals with normal SUA, and the ultrasound grading of NAFLD was higher in individuals with high SUA group than individuals with normal SUA.
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- 2020
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10. The fatty liver as testimonial of systemic diseases. Further evidence from rheumatoid arthritis and confirmation for a leading role of internal medicine.
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Di Ciaula, Agostino, Bonfrate, Leonilde, and Portincasa, Piero
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FATTY liver , *RHEUMATOID arthritis , *INTERNAL medicine - Published
- 2023
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11. Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans
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Kalliopi Pafili and Michael Roden
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Fatty liver ,Lipotoxicity ,Inflammation ,Fibrosis ,Insulin resistance ,Clinical trials ,Internal medicine ,RC31-1245 - Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) comprises hepatic alterations with increased lipid accumulation (steatosis) without or with inflammation (nonalcoholic steatohepatitis, NASH) and/or fibrosis in the absence of other causes of liver disease. NAFLD is developing as a burgeoning health challenge, mainly due to the worldwide obesity and diabetes epidemics. Scope of review: This review summarizes the knowledge on the pathogenesis underlying NAFLD by focusing on studies in humans and on hypercaloric nutrition, including effects of saturated fat and fructose, as well as adipose tissue dysfunction, leading to hepatic lipotoxicity, abnormal mitochondrial function, and oxidative stress, and highlights intestinal dysbiosis. These mechanisms are discussed in the context of current treatments targeting metabolic pathways and the results of related clinical trials. Major conclusions: Recent studies have provided evidence that certain conditions, for example, the severe insulin-resistant diabetes (SIRD) subgroup (cluster) and the presence of an increasing number of gene variants, seem to predispose for excessive risk of NAFLD and its accelerated progression. Recent clinical trials have been frequently unsuccessful in halting or preventing NAFLD progression, perhaps partly due to including unselected cohorts in later stages of NAFLD. On the basis of this literature review, this study proposed screening in individuals with the highest genetic or acquired risk of disease progression, for example, the SIRD subgroup, and developing treatment concepts targeting the earliest pathophysiolgical alterations, namely, adipocyte dysfunction and insulin resistance.
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- 2021
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12. Reversal of diet-induced hepatic steatosis by peripheral CB1 receptor blockade in mice is p53/miRNA-22/SIRT1/PPARα dependent
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Shahar Azar, Shiran Udi, Adi Drori, Rivka Hadar, Alina Nemirovski, Kiran V. Vemuri, Maya Miller, Dana Sherill-Rofe, Yhara Arad, Devorah Gur-Wahnon, Xiaoling Li, Alexandros Makriyannis, Danny Ben-Zvi, Yuval Tabach, Iddo Z. Ben-Dov, and Joseph Tam
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Obesity ,Fatty liver ,Endocannabinoids ,microRNAs ,Nuclear receptor ,Internal medicine ,RC31-1245 - Abstract
Objective: The endocannabinoid (eCB) system is increasingly recognized as being crucially important in obesity-related hepatic steatosis. By activating the hepatic cannabinoid-1 receptor (CB1R), eCBs modulate lipogenesis and fatty acid oxidation. However, the underlying molecular mechanisms are largely unknown. Methods: We combined unbiased bioinformatics techniques, mouse genetic manipulations, multiple pharmacological, molecular, and cellular biology approaches, and genomic sequencing to systematically decipher the role of the hepatic CB1R in modulating fat utilization in the liver and explored the downstream molecular mechanisms. Results: Using an unbiased normalized phylogenetic profiling analysis, we found that the CB1R evolutionarily coevolves with peroxisome proliferator-activated receptor-alpha (PPARα), a key regulator of hepatic lipid metabolism. In diet-induced obese (DIO) mice, peripheral CB1R blockade (using AM6545) induced the reversal of hepatic steatosis and improved liver injury in WT, but not in PPARα−/− mice. The antisteatotic effect mediated by AM6545 in WT DIO mice was accompanied by increased hepatic expression and activity of PPARα as well as elevated hepatic levels of the PPARα-activating eCB-like molecules oleoylethanolamide and palmitoylethanolamide. Moreover, AM6545 was unable to rescue hepatic steatosis in DIO mice lacking liver sirtuin 1 (SIRT1), an upstream regulator of PPARα. Both of these signaling molecules were modulated by the CB1R as measured in hepatocytes exposed to lipotoxic conditions or treated with CB1R agonists in the absence/presence of AM6545. Furthermore, using microRNA transcriptomic profiling, we found that the CB1R regulated the hepatic expression, acetylation, and transcriptional activity of p53, resulting in the enhanced expression of miR-22, which was found to specifically target SIRT1 and PPARα. Conclusions: We provide strong evidence for a functional role of the p53/miR-22/SIRT1/PPARα signaling pathway in potentially mediating the antisteatotic effect of peripherally restricted CB1R blockade.
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- 2020
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13. Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia
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Juan Carlos Olivares-Gazca, Gilberto David Elias-de-la-Cruz, Iván Murrieta-Álvarez, Alejandra Carmina Córdova-Ramírez, Guillermo J. Ruiz-Delgado, Yahveth Cantero-Fortiz, Montserrat Rivera-Álvarez, Guillermo J. Ruiz-Argüelles, and Andrés Aurelio León-Peña
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medicine.medical_specialty ,Cirrhosis ,Leukopenia ,business.industry ,Fatty liver ,nutritional and metabolic diseases ,Hematology ,Disease ,Neutropenia ,medicine.disease ,digestive system ,Gastroenterology ,digestive system diseases ,Serology ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Immunology and Allergy ,Platelet ,medicine.symptom ,Transient elastography ,business - Abstract
Introduction We have previously shown that some patients present thrombocytopenia (less than 100 × 109/L platelets) in non-alcoholic fatty liver disease (NAFLD). To further explore the nature of this association, we have now analyzed the association of thrombocytopenia with neutropenia (less than 0.5 × 109/L granulocytes) in NAFLD. Material and methods Persons with NAFLD were prospectively accrued in the study after February 2018. The presence of NAFLD was defined by both serologic determinations (Fibromax ®) and liver transient elastography (TE/Fibroscan ®). Results In 123 consecutive patients with NAFLD without cirrhosis, thrombocytopenia was identified in 20 (16%), whereas neutropenia was identified in 9 (7%). In the subset of 20 patients with NAFLD and thrombocytopenia, granulocytopenia was identified in 5 (25%), whereas in the subset of 9 patients with granulocytopenia, thrombocytopenia was identified in 5 (55%). We found a significant association between thrombocytopenia and both leukopenia and granulocytopenia (OR 8.25, 95% CI 1.9–34.2, p = 0.004). Conclusions Both thrombocytopenia and neutropenia were identified in persons with NAFLD and, as there is a significant relationship between these two variables, we speculate that this finding may support the possibility of hypersplenism being involved in the cytopenias found in NAFLD without cirrhosis.
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- 2022
14. Partial leptin deficiency confers resistance to diet-induced obesity in mice
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Shangang Zhao, Na Li, Yi Zhu, Leon Straub, Zhuzhen Zhang, May-Yun Wang, Qingzhang Zhu, Christine M. Kusminski, Joel K. Elmquist, and Philipp E. Scherer
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Leptin ,Partial leptin deficiency ,Leptin resistance ,Adipose tissue inflammation ,Fatty liver ,Liver fibrosis ,Internal medicine ,RC31-1245 - Abstract
Objective: Hyperleptinemia per se is sufficient to promote leptin resistance in the obese state. Leptin sensitivity can be restored by reducing circulating leptin levels within a physiologically healthy range and is a viable antiobesity and antidiabetic strategy. However, a previous study suggests that partial leptin deficiency favors diet-induced obesity and related metabolic disorders in mice, arguing that a lower leptin level may indeed promote diet-induced obesity and its associated metabolic disorders. Here, we aim to elucidate what the impact of partial leptin deficiency is on fat mass and insulin sensitivity. Methods: We used two different mouse models of partial leptin deficiency: an adipocyte-specific congenital heterozygous leptin knockout mouse line (LepHZ) and the well-established whole body heterozygous leptin knockout mouse (OBHZ). The metabolic studies of OBHZ and LepHZ mice were performed both on normal carbohydrate-rich chow diet and on a high-fat diet (HFD). Male and female mice were included in the study to account for sex-specific differences. Body weight, food intake, glucose tolerance, and insulin tolerance were tested. Histology of adipose tissue and liver tissue allowed insights into adipose tissue inflammation and hepatic triglyceride content. Immunohistochemistry was paired with RT-PCR analysis for expression levels of inflammatory markers. Results: Both OBHZ and LepHZ mice displayed reduced circulating leptin levels on the chow diet and HFD. On chow diet, male OBHZ and LepHZ mice showed elevated fat mass and body weight, while their glucose tolerance and insulin sensitivity remained unchanged. However, the inability in partially leptin-deficient mice to fully induce circulating leptin during the development of diet-induced obesity results in reduced food intake and leaner mice with lower body weight compared to their littermate controls. Importantly, a strong reduction of adipose tissue inflammation is observed along with improvements in insulin sensitivity and enhanced glucose tolerance. Additionally, partial leptin deficiency protects the mice from fatty liver and liver fibrosis. Chronically HFD-fed OBHZ and LepHZ mice remain more sensitive to exogenous leptin injection, as reflected by their reduced food intake upon an acute leptin treatment. Conclusion: In response to HFD feeding, the inability to upregulate leptin levels due to partial leptin deficiency protects mice from diet-induced obesity and metabolic dysregulation. Thus, in an obesogenic environment, maintaining lower leptin levels is highly beneficial for both obesity and diabetes management. Chronic leptin reduction represents a viable preventive strategy whose efficacy awaits clinical testing.
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- 2020
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15. New Findings Reported from Department of Internal Medicine Describe Advances in Non-Alcoholic Fatty Liver Disease (Can the FIB-4 score predict the severity of acute pancreatitis in NAFLD?).
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NON-alcoholic fatty liver disease ,FATTY liver ,INTERNAL medicine ,PANCREATITIS ,DIGESTIVE system diseases ,HEPATIC fibrosis - Abstract
A recent report discusses research findings on non-alcoholic fatty liver disease (NAFLD) and its relationship to acute pancreatitis. The study aimed to determine if the FIB-4 score, a non-invasive scoring method for diagnosing NAFLD, could predict the severity of acute pancreatitis. The study found that patients with NAFLD had higher Ranson scores and liver enzyme levels, suggesting that liver damage accompanying acute pancreatitis may worsen in patients with NAFLD. Further research is needed to explore this relationship in more depth. [Extracted from the article]
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- 2024
16. Study Data from Department of Internal Medicine Update Understanding of Fatty Liver Disease (A Common Variant That Alters Sun1 Degradation Associates With Hepatic Steatosis and Metabolic Traits In Multiple Cohorts).
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FATTY liver ,INTERNAL medicine ,NON-alcoholic fatty liver disease ,NUCLEAR membranes ,INTRACELLULAR space ,INTRACELLULAR membranes - Abstract
A recent study conducted by researchers at the Department of Internal Medicine in Ann Arbor, Michigan, has found that a common variant in the SUN1 gene is associated with hepatic steatosis (fatty liver disease) and metabolic traits. The researchers performed an association meta-analysis of nuclear envelope-related coding variants in large cohorts and found that the variant rs6461378 (SUN1 H118Y) was strongly associated with hepatic steatosis. Functional testing revealed that cells expressing the variant exhibited insulin resistance and increased lipid accumulation. These findings suggest a potential causal role for the SUN1 variant in the development of fatty liver disease and metabolic disease. [Extracted from the article]
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- 2024
17. Endocan: A Biomarker for Hepatosteatosis in Patients with Metabolic Syndrome.
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Erman, Hande, Beydogan, Engin, Cetin, Seher Irem, and Boyuk, Banu
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METABOLIC syndrome , *CARDIOVASCULAR diseases risk factors , *FATTY liver , *LIVER diseases , *INTERNAL medicine , *HEPATORENAL syndrome - Abstract
Background. Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, which has recently been mentioned as an independent cardiovascular risk factor. Objectives. Endocan is a novel molecule of endothelial dysfunction. We aimed to evaluate the associations of serum endocan levels with the hepatic steatosis index (HSI), fatty liver index (FLI), and degrees of hepatosteatosis in patients with metabolic syndrome with NAFLD. Design and Setting. This cross-sectional prospective study was performed in the outpatient clinic of an internal medicine department. Methods. The study included 40 patients with metabolic syndrome with NAFLD as noted using hepatic ultrasound and 20 healthy controls. Secondary causes of fatty liver were excluded. FLI and HSI calculations were recorded. Serum endocan level values were obtained after overnight fasting. Results. Higher values of HSI and FLI were found in the NAFLD groups than in the control groups (p < 0.001). Five (12.5%) of 20 patients with liver steatosis had grade 1 liver steatosis, 15 (37.5%) patients had grade 2 liver steatosis, and 20 (50%) patients had grade 3 liver steatosis. Serum endocan levels were lower in patients with NAFLD compared with the healthy controls (146.56 ± 133.29 pg / mL vs. 433.71 ± 298.01 pg / mL , p < 0.001). ROC curve analysis suggested that the optimum endocan value cutoff point for NAFLD was 122.583 pg/mL (sensitivity: 71.79%, specificity: 90%, PPV: 93.3%, and NPV: 62.1%). Conclusion. Serum endocan concentrations are low in patients with NAFLD, and the optimum cutoff point is 122.583 pg/mL. HSI and FLI were higher in patients with NAFLD; however, there was no correlation with serum endocan. [ABSTRACT FROM AUTHOR]
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- 2020
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18. Wilson disease diagnosed incidentally by targeted gene panel sequencing in a Korean boy with severe obesity
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Dong-Kyu Jin, Ji-Yeon Kim, Sung Yoon Cho, Sae-Mi Lee, Mi Jin Kim, Ari Song, Min Sun Kim, and Minji Im
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medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Fatty liver ,Disease ,Severe obesity ,medicine.disease ,Obesity ,Gastroenterology ,Hepatic Involvement ,Liver disease ,Internal medicine ,Gene panel ,Pediatrics, Perinatology and Child Health ,medicine ,Differential diagnosis ,business - Abstract
Wilson disease (WD) is a relatively common genetic hepatic disease in children that is characterized by excessive copper accumulation, predominantly in the liver and brain. It is an autosomal recessive disease caused by the mutation of ATP7B that is potentially fatal if diagnosed late or untreated owing to degenerative aspects in the brain. In the early phase of WD, its initial presentation may include a mild hepatic involvement. WD may be overlooked as a cause of liver disease due to severe obesity, but should not be excluded from the differential diagnosis. We report a case of WD with severe obesity and fatty liver diagnosed in the early phase by targeted gene panel sequencing. We reviewed the endocrine problems associated with WD. Early suspicion of WD is important to improve prognosis.
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- 2022
19. Molecular, biochemical, and histopathological effects of long-term low and high-percentage fructose consumption on the liver in rats
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Tuncer Kutlu, Akın Yakin, Şule Yurdagül Özsoy, and Hüseyin Özkan
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Consumption (economics) ,medicine.medical_specialty ,General Veterinary ,Fructose ,Term (time) ,fruktoz ,inflamasyon ,lipogenez ,NAFLD ,yağlı karaciğer ,fatty liver ,fructose ,inflammation ,lipogenesis ,chemistry.chemical_compound ,Veterinary ,Endocrinology ,chemistry ,Internal medicine ,medicine ,Veteriner Hekimlik ,Animal Science and Zoology - Abstract
Diyetlerdeki karbonhidrat çeşitleri hakkında bilimsel tartışmalar devam etmektedir. Fruktoz, gıda ürünlerinde yaygın olarak kullanılmaktadır. Çalışmada, ratlarda düşük ve yüksek fruktoz solüsyonlarının lipogenik ve inflamatuar etkileri araştırılmıştır. Hayvanlar, 10 hafta süreyle fruktoz solüsyonları ile beslenmiştir. Gruplar: Con (Kontrol), F15 (Fruktoz %15), F30 (Fruktoz %30), F60 (Fruktoz %60) şeklinde olmuştur. F60 en hafif grupken, F30 en ağır grup olarak belirlenmiştir. Trigliserit seviyeleri tüm deneme gruplarında Con'dan önemli ölçüde daha yüksek olmuştur (P, The aim of this study was to investigate the lipogenic and inflammatory effects of low and high percentage fructose solutions in rats. Wistar albino rats were fed with fructose solutions for 10 weeks. The groups were as follows: Cont (Control), F15 (Fructose 15%), F30 (Fructose 30%), and F60 (Fructose 60%). Rats' body weights were measured weekly. Also, lipogenic and inflammatory gene expression levels, biochemical parameters, and histopathological changes in the liver were investigated. After 10 weeks, it was observed that the animals in the F60 were the heaviest, while the animals in the F30 were the lightest. In all experimental groups, triglycerides were significantly higher than those of controls (P
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- 2022
20. Association of the Metabolic Dysfunction-Associated Fatty Liver Disease with Serum Uric Acid-to-Creatinine Ratio
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A. Lum Han and Hee Kyung Lee
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Fatty Liver ,Male ,Non-alcoholic Fatty Liver Disease ,Creatinine ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Humans ,Female ,Retrospective Studies ,Uric Acid - Published
- 2022
21. Circulating PCSK7 Level is Independently Associated with Obesity, Triglycerides Level and Fatty Liver Index in a General Population without Medication
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Yu Kataoka, Ryo Nishikawa, Marenao Tanaka, Masato Furuhashi, Masayuki Koyama, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Akiko Sakai, and Yukimura Higashiura
- Subjects
Male ,medicine.medical_specialty ,Iron ,Population ,Chronic liver disease ,Cohort Studies ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Internal Medicine ,Humans ,Medicine ,Obesity ,Subtilisins ,education ,Blood urea nitrogen ,Triglycerides ,education.field_of_study ,business.industry ,PCSK9 ,Biochemistry (medical) ,Fatty liver ,gamma-Glutamyltransferase ,medicine.disease ,Endocrinology ,Female ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine ,business ,Body mass index ,Dyslipidemia - Abstract
Aim Dyslipidemia and altered iron metabolism are typical features of non-alcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7), a transmembrane-anchored endonuclease, is associated with triglycerides level and processing of transferrin receptor 1. However, the significance of circulating PCSK7 has not been fully addressed, though prosegment PCSK7 is secreted from cells. We investigated the associations of plasma PCSK7 level with several parameters. Methods Plasma PCSK7 concentration was measured in 282 subjects (male/female: 126/156) without medication of the Tanno-Sobetsu Study, a population-based cohort study. Results There was no significant sex difference in PCSK7 level. Current smoking habit, but not alcohol drinking habit, was associated with increased PCSK7 level. PCSK7 concentration was negatively correlated with age and blood urea nitrogen and was positively correlated with body mass index (BMI) and levels of γ-glutamyl transpeptidase (γGTP), triglycerides and fatty liver index (FLI), which is calculated by BMI, waist circumference and levels of γGTP and triglycerides, as a noninvasive and simple predictor of NAFLD. There were no significant correlations of PCSK7 level with levels of iron and plasma PCSK9, a secreted PCSK family member and a regulator of low-density lipoprotein cholesterol level. Multivariable regression analyses after adjustment of age, sex and current smoking habit showed that PCSK7 concentration was independently associated with BMI (β=0.130, P=0.035), triglycerides (β=0.141, P=0.027) or FLI (β=0.139, P=0.030). Conclusions Plasma PCSK7 concentration is independently associated with chronic liver disease including obesity and elevated triglycerides level in a general population of individuals who had not regularly taken any medications.
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- 2022
22. Hepatic steatosis and advanced fibrosis are independent predictors of mortality in acute myocardial infarction without standard modifiable risk factors
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Nicholas WS Chew, Gemma A Figtree, Gwyneth Kong, Steve Vernon, Mark Muthiah, Cheng Han Ng, Mark Y Chan, and Poay H Loh
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Fatty Liver ,Endocrinology ,Risk Factors ,Endocrinology, Diabetes and Metabolism ,Myocardial Infarction ,Internal Medicine ,Humans ,Fibrosis - Published
- 2022
23. Hepatic steatosis and development of type 2 diabetes: Impact of chronic hepatitis B and viral specific factors
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Ming-Whei Yu, Yi Wen Huang, Chih-Lin Lin, Wan-Jung Wu, Chun-Jen Liu, Chih-Feng Wu, and Jui-Ting Hu
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Hepatitis B virus ,HBsAg ,medicine.medical_specialty ,Cirrhosis ,Population ,Gastroenterology ,Cohort Studies ,Hepatitis B, Chronic ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Humans ,education ,education.field_of_study ,Hepatitis B Surface Antigens ,business.industry ,Liver Neoplasms ,Fatty liver ,General Medicine ,medicine.disease ,Impaired fasting glucose ,Diabetes Mellitus, Type 2 ,Steatosis ,business ,Viral load - Abstract
Background Chronic hepatitis B (CHB) was associated with a lower prevalence of nonalcoholic fatty liver disease (NAFLD). The impact of CHB on the link between NAFLD and type 2 diabetes (T2D) and related virological implications remain unclear. Methods We recruited 2255 middle–to older–aged individuals who were examined serially for hepatic steatosis by ultrasonography and blood biochemistry as part of a population-based hepatocellular-carcinoma cohort study. In CHB patients, hepatitis B surface antigen (HBsAg) seroclearance and variation in viral load trajectory were also evaluated. Results During the average follow-up of 6 years, 168 participants developed T2D. CHB, as compared with uninfected subjects, was associated with lower risks for both new development and persistence of hepatic steatosis. Furthermore, the risk of steatosis decreased with higher levels of past viral load trajectories (p for trend = 0.0002). However, concomitant steatosis at baseline in CHB patients was still significantly associated with a 1.98-fold increased risk for T2D after multivariate adjustment including age, impaired fasting glucose, cirrhosis, and time-varying body mass index, although CHB reduced the propensity of hepatic steatosis to develop diabetes, especially for patients with high levels of past viral-load trajectory. In CHB, the functional cure of HBV infection, as indicated by HBsAg seroclearance, was associated with a 1.41-fold (95% CI 1.12–1.79) increased risk of steatosis. In addition, the increased risk for progressive impairment of glucose metabolism due to steatosis was especially prominent after HBsAg seroclearance. Conclusion The data showed that HBV interferes with fatty liver disease and modulates its related T2D risk, offering additional insight into the interplay between NAFLD and CHB.
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- 2022
24. Association of Hepatic Steatosis with Adipose and Muscle Mass and Distribution in Children
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Ghattas J. Malki, Nidhi P. Goyal, Patricia Ugalde-Nicalo, Lauren F. Chun, Jasen Zhang, Ziyi Ding, Yingjia Wei, Cynthia Knott, Danielle Batakis, Walter Henderson, Claude B. Sirlin, Michael S. Middleton, and Jeffrey B. Schwimmer
- Subjects
nonalcoholic fatty liver disease ,muscle ,Endocrinology, Diabetes and Metabolism ,Chronic Liver Disease and Cirrhosis ,Medical Biotechnology ,Clinical Sciences ,Intra-Abdominal Fat ,Oral and gastrointestinal ,Endocrinology & Metabolism ,Internal Medicine ,Humans ,Abdominal ,Obesity ,Child ,Metabolic and endocrine ,Adiposity ,Nutrition ,Pediatric ,adipose ,Muscles ,hepatic steatosis ,Liver Disease ,Original Articles ,Magnetic Resonance Imaging ,Fatty Liver ,Liver ,Public Health and Health Services ,Biomedical Imaging ,Digestive Diseases ,MRI-PDFF - Abstract
Background: Pediatric studies have shown associations between hepatic steatosis and total body fat, visceral fat, and lean mass. However, these associations have not been assessed simultaneously, leaving their relative importance unknown. Objective: To evaluate associations between hepatic steatosis and total-body adiposity, visceral adiposity, and lean mass in children. Method: In children at risk for fatty liver, hepatic steatosis, adipose, and lean mass were estimated with magnetic resonance imaging and dual-energy X-ray absorptiometry. Results: Two hundred twenty-seven children with mean age 12.1 years had mean percent body fat of 38.9% and mean liver fat of 8.4%. Liver fat was positively associated with total-body adiposity, visceral adiposity, and lean mass (P
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- 2023
25. A New Oral Model to Assess Postprandial Lactate Production Rate
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Jacopo Bonet, Nicola Santoro, Brittany Galuppo, and Chiara Dalla-Man
- Subjects
Blood Glucose ,obesity ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Biomedical Engineering ,prediabetes ,diabetes ,identifiability ,parameter estimation ,Physiological modeling ,Article ,chemistry.chemical_compound ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,Medicine ,Humans ,Insulin ,Glycolysis ,Prediabetes ,Lactic Acid ,Child ,business.industry ,Fatty liver ,Acetyl-CoA ,Glucose Tolerance Test ,medicine.disease ,Postprandial Period ,Endocrinology ,Postprandial ,Glucose ,chemistry ,Insulin Resistance ,business - Abstract
Objective: Pediatric obesity predisposes children and adolescents to early onset insulin resistance and dysglycemia. In the last 20 years this has led to a rise in the prevalence of prediabetes, diabetes and fatty liver in youngsters, due to the high degree of insulin resistance experienced by these patients and the consequent high availability of glucose. As glucose accesses the liver, it is partly metabolized through glycolysis, whose main product is pyruvate that is then converted into Acetyl CoA and lactate. Therefore, lactate production rate (LPR) represents the best proxy for the assessment of glycolysis. Since to date there are not methods to estimate postprandial LPR, here we proposed a novel oral glucose-lactate model to estimate LPR during an oral glucose tolerance test and tested it in 24 youth with and without obesity. Methods: The model is based on the oral glucose minimal model and assumes that LPR is a fraction (fr) of glucose disposal rate, proportional to glucose concentration and controlled by insulin action. Results: The model well fitted the glucose and lactate data, and provided both precise parameter estimates (e.g. fr=22.5 [12.6-54.1]%, median [IQR]), CV=18 [13-25]%) and LPR time course. Conclusions: The proposed model is a valid tool to assess LPR, and thus glycolysis, during OGTT in nondiabetic subjects. Significance: The proposed methodology will allow to assess postprandial LPR in simple and cost-effective way.
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- 2023
26. Metabolic Dysfunction-Associated Fatty Liver Disease Predicts Long-term Mortality and Cardiovascular Disease
- Author
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Bo Kyung Koo, Nam H. Cho, Joon Ho Moon, and Won Kim
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Adult ,Male ,medicine.medical_specialty ,Overweight ,Gastroenterology ,Cohort Studies ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Prospective Studies ,Aged ,Hepatology ,business.industry ,Fatty liver ,Hazard ratio ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,Obesity ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,medicine.symptom ,business ,Body mass index ,Cohort study - Abstract
Background/aims We investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study. Methods Individuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions: overweight/obesity (body mass index ≥23 kg/m2), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis. Results Among 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85). Conclusions MAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.
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- 2022
27. Association between fat‐infiltrated axillary lymph nodes on screening mammography and cardiometabolic disease
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Roberta M. diFlorio-Alexander, Qingyuan Song, Ryan T Sieberg, Sohum D Patel, Saeed Hassanpour, Saif M Ansari, Todd A. MacKenzie, Michael J Margron, and Margaret R. Karagas
- Subjects
medicine.medical_specialty ,Nutrition and Dietetics ,Receiver operating characteristic ,Axillary lymph nodes ,business.industry ,Medical record ,Endocrinology, Diabetes and Metabolism ,Fatty liver ,Odds ratio ,Disease ,medicine.disease ,medicine.anatomical_structure ,Internal medicine ,medicine ,business ,Stroke ,Dyslipidemia - Abstract
ObjectiveEctopic fat deposition within and around organs is a stronger predictor of cardiometabolic disease status than body mass index. Fat deposition within the lymphatic system is poorly understood. This study examined the association between the prevalence of cardiometabolic disease and ectopic fat deposition within axillary lymph nodes (LNs) visualized on screening mammograms.MethodsA cross-sectional study was conducted on 834 women presenting for full-field digital screening mammography. The status of fat-infiltrated LNs was assessed based on the size and morphology of axillary LNs from screening mammograms. The prevalence of cardiometabolic disease was retrieved from the electronic medical records, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, high blood glucose, cardiovascular disease, stroke, and non-alcoholic fatty liver disease.ResultsFat-infiltrated axillary LNs were associated with a high prevalence of T2DM among all women (adjusted odds ratio: 3.92, 95% CI: [2.40, 6.60], p-value < 0.001) and in subgroups of women with and without obesity. Utilizing the status of fatty LNs improved the classification of T2DM status in addition to age and BMI (1.4% improvement in the area under the receiver operating characteristic curve).ConclusionFat-infiltrated axillary LNs visualized on screening mammograms were associated with the prevalence of T2DM. If further validated, fat-infiltrated axillary LNs may represent a novel imaging biomarker of T2DM in women undergoing screening mammography.
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- 2022
28. Liver biopsy complication rates in patients with non-alcoholic fatty liver disease
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Magnus McLeod, Felix Zhou, and Ashley E. Stueck
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Fatty liver ,Non alcoholic ,General Medicine ,Disease ,medicine.disease ,Gastroenterology ,Fibrosis ,Internal medicine ,Liver biopsy ,Biopsy ,medicine ,In patient ,Complication ,business - Abstract
BACKGROUND: With new treatments for non-alcoholic fatty liver disease (NAFLD) on the horizon, it will be important to risk-stratify patients based on degree of fibrosis to allocate treatment to those at highest risk. No studies have examined the complication rates of liver biopsies in patients with NAFLD in the outpatient setting. METHODS: We conducted a retrospective chart review of all outpatient elective liver biopsies for NAFLD at a tertiary care centre over a 10-year period. Demographic variables and stage of fibrosis were recorded. Complications up to 1 week post-procedure were recorded. We used univariate logistic regression models to estimate the odds of major complications by fibrosis stage, age, sex, platelets, and international normalized ratio (INR). RESULTS: There were 582 biopsies reviewed in total. The mean age was 53 years. There was an even proportion of males to females. The mean fibrosis stage was 1.9; platelet count was 223.9, INR was 1, and partial thromboplastin time (PTT) was 31. Major complications occurred in 8 out of 582 biopsies (1.4%). Bleeding accounted for 6 of the major complications observed, while infection and pneumoperitoneum each occurred once. There were no statistically significant associations between age (odds ratio [OR] 0.97, 95% CI 0.92–1.03), female sex (OR 1.00, 95% CI 0.25–4.04), platelet count 1.3 (OR 0.47, 95% CI 0.057–3.85), fibrosis stage, and complication rate. CONCLUSIONS: Our results are consistent with previous studies examining complication rates in other patient populations and clinical settings and support the overall safety of liver biopsies.
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- 2022
29. Hepatic Steatosis: CT-Based Prevalence in Adults in China and the United States and Associations With Age, Sex, and Body Mass Index
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Glen M. Blake, Shaoqi Xu, Peter M Graffy, Kai Li, Haibo Qu, Zhe Guo, Xiaoguang Cheng, Ronald M. Summers, Jun Zhou, Perry J. Pickhardt, Baoqing Li, Yonghong Jiang, Jiman Shao, Yizhong Chen, and Veit Sandfort
- Subjects
Adult ,Male ,China ,medicine.medical_specialty ,Abdominal ct ,Population ,Body Mass Index ,Internal medicine ,Liver fat ,Prevalence ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,education ,Retrospective Studies ,education.field_of_study ,business.industry ,Retrospective cohort study ,General Medicine ,medicine.disease ,Fatty Liver ,Cohort ,Female ,Steatosis ,Tomography, X-Ray Computed ,business ,Body mass index ,Ct measurements - Abstract
Background: Calibrated CT fat fraction (FFCT) measurements derived from non-enhanced abdominal CT reliably reflect liver fat content, allowing largescale population-level investigations of steatosis prevalence and associations. Objective: To compare prevalence of hepatic steatosis, assessed by calibrated CT measurements, between population-based Chinese and U.S. cohorts, and to investigate in these populations the relationship of steatosis with age, sex, and body mass index (BMI). Methods: This retrospective study included 3176 adults (1985 women, 1191 men) from seven Chinese provinces and 8748 adults (4834 women, 3914 men) from a single U.S. medical center, drawn from earlier studies. All participants were at least 40 years old and underwent unenhanced abdominal CT for the earlier studies. Liver fat content measurements on CT were cross-calibrated to MRI proton density fat fraction measurements using phantoms and expressed as adjusted FFCT. Mild, moderate, and severe steatosis were defined as adjusted FFCT of 5.0%-14.9%, 15.0%-24.9%, and ≥25.0%, respectively. The two cohorts were compared. Results: Median adjusted FFCT was for women 4.7% and 4.8%, and for men 5.8% and 6.2%, in the Chinese and U.S. cohorts, respectively. Steatosis prevalence was for women 46.3% and 48.7%, and for men 58.9% and 61.9%, in the Chinese and U.S. cohorts, respectively. Severe steatosis prevalence was for women 0.9% and 1.8%, and for men, 0.2% and 2.6%, in the Chinese and U.S. cohorts, respectively. Adjusted FFCT did not vary across age decades in women or men in the Chinese cohort, though increased across age decades in women and men in the U.S. cohort. Adjusted FFCT and BMI exhibited weak correlation (r=0.312-0.431). Among participants with normal BMI, 36.8% and 38.5% of those in the Chinese and U.S. cohorts had mild steatosis, and 3.0% and 1.5% had moderate or severe steatosis, respectively. Among U.S. participants with BMI ≥40.0, 17.7% had normal liver content. Conclusion: Steatosis and severe steatosis had higher prevalence in the U.S. than Chinese cohort in both women and men. BMI did not reliably predict steatosis. Clinical Impact: The findings provide new information on the dependence of hepatic steatosis on age, sex, and BMI.
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- 2022
30. Efecto de la dieta mediterránea sobre indicadores histológicos y pruebas de imagen en enfermedad de hígado graso no alcohólico
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Yeily Saavedra, Valentina Mena, and Kathleen Priken
- Subjects
medicine.medical_specialty ,Hepatology ,medicine.diagnostic_test ,Mediterranean diet ,business.industry ,Fatty liver ,Gastroenterology ,Magnetic resonance imaging ,medicine.disease ,law.invention ,Randomized controlled trial ,law ,Liver biopsy ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Observational study ,Transient elastography ,business - Abstract
Aim To analyze the scientific evidence regarding to the effect of the Mediterranean diet on the imaging tests and biopsy characteristics in subjects with non-alcoholic fatty liver disease (NAFLD). Methods A bibliographic search was carried out in this narrative review in Pubmed and Web of Science databases, considering studies published between 2011 and 2020, in English or Spanish, randomized clinical trials and observational studies in patients with a diagnosis of NAFLD, in subjects over 18years of age of both sexes. Results In the observational studies found, an inverse association between adherence to a Mediterranean diet and liver damage stands out, while in the intervention studies with measurement of liver biopsy a 4.4% reduction in intrahepatic lipids and with magnetic resonance a reduction between 4.2 and 10.2% was found. In experimental studies with ultrasound measurement, the proportion of people with moderate (6-16%) and severe (25%) degree decreased and the studies with transient elastography showed a decrease in liver stiffness between 0.5 and 2.1kPa. Conclusions The Mediterranean diet contributes to the treatment of NAFLD, which is manifested in the liver and histological imaging tests characteristics.
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- 2022
31. Nonalcoholic Steatohepatitis: A Rapidly Increasing Indication for Liver Transplantation in India
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Akila Rajakumar, Ilankumaran Kaliamoorthy, Ashwin Rammohan, Kumar Palaniappan, Mohamed Rela, Rajesh Rajalingam, Dinesh Jothimani, Silas Danielraj, Gomathy Narasimhan, Swetha Palanisamy, and Hemalatha Ramachandran
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,medicine.medical_treatment ,Fatty liver ,Prevalence ,Hepatitis C ,Hepatitis B ,Liver transplantation ,medicine.disease ,Gastroenterology ,digestive system diseases ,Internal medicine ,medicine ,Original Article ,Steatohepatitis ,business ,Viral hepatitis ,Survival analysis - Abstract
BACKGROUND AND AIMS: Recently, there has been a considerable increase in patients with nonalcoholic fatty liver disease. Availability of high-efficacy drugs for hepatitis B and hepatitis C virus (HCV) infection may have changed the disease prevalence. We aimed to study the impact of this changing epidemiology in patients undergoing liver transplantation (LT) over a 10-year period. METHODS: The study population was stratified into Period 1 (2009–2014) and Period 2 (2015–2019). Demographics, indications for LT and changes in the epidemiology between two periods were analysed. Aetiology-based posttransplant survival analysis was carried out. RESULTS: Indication for LT among 1017 adult patients (277 in Period 1 and 740 in Period 2) showed a significant increase in nonalcoholic steatohepatitis (NASH; 85 [30.7%] and 311 [42%]; P = 0.001), decrease in hepatitis C (49 [17.7%] and 75 [10.1%]; P = 0.002), and increase in hepatocellular carcinoma from Period 1 to Period 2 (13 [26.5%] to 38 [50.7%]; P = 0.009) among HCV patients. Patients transplanted for NASH had a lower 5-year survival compared with viral hepatitis (75.9% vs 87.4%; P = 0.03). There was a strong association between coronary artery disease and NASH (hazard ratio = 1.963, 95% confidence interval, 1.19–3.22). CONCLUSION: NASH is the leading indication for liver transplantation in India, surpassing viral hepatitis in recent years.
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- 2022
32. The safety and efficacy evaluation of sodium-glucose co-transporter 2 inhibitors for patients with non-alcoholic fatty liver disease: An updated meta-analysis
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Yuzhen Liang, Yunhua Liao, Zichun Huang, Ning Xia, and Manqiu Mo
- Subjects
medicine.medical_specialty ,Population ,Cochrane Library ,Gastroenterology ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Diabetes mellitus ,Humans ,Medicine ,Adverse effect ,education ,Sodium-Glucose Transporter 2 Inhibitors ,education.field_of_study ,Symporters ,Hepatology ,business.industry ,Sodium ,Fatty liver ,medicine.disease ,Fibrosis ,Glucose ,Diabetes Mellitus, Type 2 ,Meta-analysis ,Relative risk ,business ,Body mass index - Abstract
BACKGROUND In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been increasingly used in the treatment of patients with non-alcoholic fatty liver disease (NAFLD). This updated meta-analysis aimed to evaluate the efficacy and safety of SGLT2is for patients with NAFLD. METHODS PubMed, Embase, Cochrane Library, Web of Science, Wan Fang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to April 30, 2021. Values of weighted mean differences (WMDs) and risk ratios (RRs) were determined for continuous and dichotomous outcomes, respectively. RESULTS A total of 1,498 patients with NAFLD from 20 studies were included for further analysis. Pooled analyses indicated significant improvements in body mass index [WMD: -0.84 kg/m2, 95% CI (-1.09, -0.60)], alanine aminotransferase [WMD: -4.36 U/L, 95% CI (-7.17, -1.54)], aspartate aminotransferase [WMD: -2.94 U/L, 95% CI (-5.33, -0.55)], fasting plasma glucose [WMD: -4.08 mmol/L, 95% CI (-6.21, -1.95)] and fibrosis-4 index [WMD: -0.08, 95% CI (-0.11, -0.05)] following SGLT2i treatment (p
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- 2022
33. MRI-based (MAST) score accurately identifies patients with NASH and significant fibrosis
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Nabil Noureddin, Emily Truong, Maha Guindi, Naim Alkhouri, Tsuyoshi Todo, Mazen Noureddin, Rola Saouaf, Stephen A. Harrison, Jeffrey Gornbein, and Ju Dong Yang
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Biopsy ,Gastroenterology ,Liver disease ,Non-alcoholic Fatty Liver Disease ,Fibrosis ,Internal medicine ,Nonalcoholic fatty liver disease ,Humans ,Medicine ,Blood test ,Aspartate Aminotransferases ,Hepatology ,medicine.diagnostic_test ,business.industry ,Fatty liver ,medicine.disease ,Magnetic Resonance Imaging ,Liver ,Liver biopsy ,Disease Progression ,business ,Transient elastography ,Body mass index - Abstract
Among the large population of patients with non-alcoholic fatty liver disease (NAFLD), identifying those with fibrotic non-alcoholic steatohepatitis (Fibro-NASH) is a clinical priority, as these patients are at the highest risk of disease progression and will benefit most from pharmacologic treatment. MRI-based proton density fat fraction (MRI-PDFF) and MR elastography (MRE) can risk-stratify patients with NAFLD by assessing steatosis and fibrosis, respectively. We developed a highly specific MRI-based score to identify patients with Fibro-NASH.This analysis included derivation (n = 103) and validation (n = 244) cohorts of patients who underwent MRI, liver biopsy, transient elastography, and laboratory testing for NAFLD from 2016-2020 in 2 tertiary care centers. To identify Fibro-NASH, a formula was developed based on MRI-PDFF, MRE, and a third variable with highest balanced accuracy per logistic regression. The MRI-aspartate aminotransferase (MAST) score was created and compared to NAFLD fibrosis (NFS), Fibrosis-4 (FIB-4), and FibroScan-aspartate aminotransferase (FAST) scores.The MAST score demonstrated high performance and discrimination in the validation cohort (AUC 0.93; 95% CI 0.88-0.97). In the validation cohorts, the 90% specificity cut-off of 0.242 corresponded to a sensitivity of 75.0%, positive predictive value (PPV) of 50.0% and negative predictive value (NPV) of 96.5%, whereas the 90% sensitivity cut-off of 0.165 corresponded to a specificity of 72.2%, PPV of 29.4%, and NPV of 98.1%. Compared to NFS and FIB-4, MAST resulted in fewer patients having indeterminate scores and an overall higher AUC. Compared to FAST, MAST exhibited a higher AUC and overall better discrimination.The MAST score is an accurate, MRI-serum-based score that outperforms previous scores in non-invasively identifying patients at higher risk of Fibro-NASH.Identifying patients with non-alcoholic steatohepatitis and significant fibrosis - who need treatment and are at risk of clinical liver-related outcomes - is a clinical priority. We developed a more accurate score using MRI-based technologies and a laboratory blood test (aspartate aminotransferase) that outperforms previous non-invasive scores for the identification of patients at higher risk of liver disease progression.
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- 2022
34. Reply to: non-invasive tests and advanced chronic liver disease in NAFLD: two steps forward and one step back?
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Michael Pavlides, Ferenc E. Mózes, and Stephen A. Harrison
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Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Carcinoma, Hepatocellular ,medicine.diagnostic_test ,business.industry ,Non invasive ,Fatty liver ,Liver Neoplasms ,Gastroenterology ,Fibrosis stage ,medicine.disease ,Chronic liver disease ,Advanced fibrosis ,Liver ,Non-alcoholic Fatty Liver Disease ,Liver biopsy ,Internal medicine ,Hepatocellular carcinoma ,medicine ,Humans ,business - Abstract
We appreciate the interest in our study by Majumdar and Tsochatzis1 and welcome the opportunity to provide some clarifications. The literature to date has examined non-invasive test (NIT) algorithms to rule-in and rule-out advanced fibrosis (AF). The main use of such algorithms is to identify those at low risk of AF who can be managed in primary care. We propose an algorithm2 where the rule-out cut-offs remain optimised for AF, whereas the rule-in cut-offs are optimised for cirrhosis. The false-negative (FN) rate of 10% in our proposed algorithm refers to the FN rate for AF and not cirrhosis as Majumdar and Tsochatzis state in their letter.1 Only 18/570 (3%) of patients with cirrhosis are missed using our proposed algorithm (table 1). View this table: Table 1 Number of patients with fibrosis stage F0–2, F3 and F4 according to LSM cut-offs recommended by the Baveno 6 consensus (10 and 15 kPa) and our previous paper (8 and 20, and 8 and 28 kPa) We also argue2 that patients with NITs above the rule-in cut-off for AF should undergo liver biopsy to identify those with cirrhosis who should undergo …
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- 2023
35. Impact of Donor and Recipient Clinical Characteristics and Hepatic Histology on Steatosis/Fibrosis Following Liver Transplantation
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Sandy Feng, Michele DesMarais, Abraham Shaked, K. Rajender Reddy, Oren Shaked, Jeffrey D. Punch, Jack Demetris, Jorge Reyes, Peter H. Sayre, Goran B. Klintmalm, Whitney Jackson, Josh Levitsky, and Bao-Li Loza
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,medicine.medical_treatment ,Chronic Liver Disease and Cirrhosis ,Liver transplantation ,Gastroenterology ,Medical and Health Sciences ,Article ,Hepatitis ,Hepatitis - C ,Fibrosis ,Clinical Research ,Internal medicine ,Biopsy ,medicine ,Living Donors ,Humans ,Transplantation ,medicine.diagnostic_test ,business.industry ,Liver Disease ,Organ Transplantation ,medicine.disease ,Liver Transplantation ,Fatty Liver ,Infectious Diseases ,Emerging Infectious Diseases ,Good Health and Well Being ,Treatment Outcome ,Liver biopsy ,Surgery ,Metabolic syndrome ,Steatosis ,Steatohepatitis ,Hepatic fibrosis ,business ,Digestive Diseases - Abstract
BackgroundDeceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients.MethodsUsing the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected. Liver biopsies were taken from the donor liver at transplant, and from recipients per protocol and for-cause (ie, abnormal transaminases and to rule out rejection) and were interpreted by a central pathologist.ResultsOne hundred eighty-three paired donor/recipients liver biopsies at the time of transplant and posttransplant follow-up (median time 582 d; average time to last biopsies was 704 d [SD ± 402 d]) were analyzed. Donor steatosis did not influence recipient steatosis or fibrosis. Ten of 183 recipients had steatohepatitis on the last biopsy. Recipient body mass index at the time of liver biopsy was the most influential factor associated with posttransplant steatosis. Both donor and recipient metabolic syndrome features were not associated with graft steatosis. Untreated hepatitis C viral (HCV) infection was the most influential factor associated with the development of allograft fibrosis.ConclusionsIn a large experience evaluating paired donor and recipient characteristics, recipient body mass index at the time of liver biopsy was most significantly associated with posttransplant steatosis. Untreated HCV etiology influenced graft fibrosis. Thus relative to untreated HCV, hepatic fibrosis in those with steatosis/steatohepatitis is less common though long-term follow-up is needed to determine the course of posttransplant fibrosis. Emphasis on recipient weight control is essential.
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- 2023
36. Adiponectin alleviates non-alcoholic fatty liver injury via regulating oxidative stress in liver cells
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Tansheng Chen, Qin Yang, Wenwen Ma, Yi Li, Shanshan Zhang, and Xue Feng
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medicine.medical_specialty ,animal structures ,Triglyceride ,Adiponectin ,biology ,Fatty liver ,General Medicine ,Glutathione ,Malondialdehyde ,medicine.disease ,medicine.disease_cause ,Superoxide dismutase ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,biology.protein ,hormones, hormone substitutes, and hormone antagonists ,Oxidative stress - Abstract
BACKGROUND To investigate the role of adiponectin in nonalcoholic fatty liver cell model and its mechanism. METHODS The serum were collected from patients with nonalcoholic fatty liver disease and healthy controls. Then the expression of APN in the serum was detected using APN kit. Furthermore, an in vitro model of NAFLD was established using mixed fatty acids treated HepG2 cells, and APN was highly expressed in the culture solution to a concentration of 10 μg/mL. The normal control group (Normal) was normal cells, the model group (NAFLD) was mixed fatty acids treated HepG2 cells, the experimental group (NAFLD+APN) was model cells transfected with high APN expression, and the negative control group (NAFLD+PBS) was model cells transfected with PBS. The expression of NOX2 in each group was detected by Western blot. The corresponding kit was used to detect the level of triglyceride (TG), the activity of superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the ratio of GSH/GSSG in each group of cells. RESULTS The expression level of APN was greatly decreased in the serum of NAFLD patients (p
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- 2023
37. Inflammatory-nutritional scores in the diagnosis of NASH and liver fibrosis
- Author
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Silvia Palmisano, Nicolò de Manzini, Natasa Samardzic, Biagio Casagranda, Gioia Pozza, Fabiola Giudici, Pozza, Gioia, Samardzic, Natasa, Giudici, Fabiola, Casagranda, Biagio, DE Manzini, Nicolò, and Palmisano, Silvia
- Subjects
medicine.medical_specialty ,Sleeve gastrectomy ,obesity ,medicine.medical_treatment ,Liver fibrosis ,Population ,NAFLD ,Obesity ,Inflammatory-nutritional scores ,Non-invasive diagnosis ,Disease ,Gastroenterology ,Non-Alcoholic Steatohepatiti ,Internal medicine ,medicine ,Non-Alcoholic Steatohepatitis ,inflammatory markers ,education ,Pathological ,Liver injury ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Fatty liver ,General Medicine ,medicine.disease ,inflammatory marker ,Liver biopsy ,Steatohepatitis ,business - Abstract
Background The aim of the present study was to investigate the possible correlation between various inflammation-nutritional scores to histological determined Non-Alcoholic Steatohepatitis (NASH) and other liver injury suggestive for Non-Alcoholic Fatty Liver Disease (NAFLD) in a bariatric population. Methods We evaluated consecutively and retrospectively all the patients referred to the department of bariatric surgery in Trieste, Italy. Inflammation-nutritional scores were calculated starting from pre-operative hematologic data. Liver biopsy was performed at the time of bariatric surgery (sleeve gastrectomy or gastric bypass) and pathological assessment was performed using Kleiner-Brunt staging system (NAS score). Results Glasgow Prognostic Score/modified Glasgow Prognostic Score (GPS/ mGPS) and Prognostic Index (PI) were associated to the diagnosis of NASH (p= 0,024 and p=0,03 respectively). The presence of perisinusoidal and/or periportal fibrosis was correlated to Prognostic Nutritional Index (PNI) and Platelet-to-Lymphocyte ratio (PLR) values (p=0,02 and p=0,009 respectively). Conclusions GPS/mGPS and PI are statistically associated to the histological diagnosis of NASH. Further studies on large series are needed to better understand the relationship between these serum markers and liver injury in obese patients.
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- 2023
38. Metabolic Messengers: bile acids
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Alessia Perino and Kristina Schoonjans
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intestinal microbiota ,diet-induced obesity ,gut microbiota ,Biochemical Phenomena ,Endocrinology, Diabetes and Metabolism ,energy-expenditure ,Cell Biology ,Bile Acids and Salts ,fxr ,Liver ,Physiology (medical) ,body-weight ,Internal Medicine ,nuclear receptor ,chenodeoxycholic acid ,gastric bypass ,Signal Transduction ,fatty liver - Abstract
Bile acids (BAs) are amphipathic steroid acids whose production and diversity depend on both host and microbial metabolism. These metabolites have emerged as biologically active signalling molecules that inform organs of nutrient availability. Their actions, through activation of the dedicated BA receptors FXR and TGR5, control the body's integrated physiological metabolic responses. Alterations in BA abundance or signalling are associated with metabolic diseases including obesity, type 2 diabetes, non-alcoholic steatohepatitis and atherosclerosis. Consequently, modulation of the BA pool could be a valid therapeutic approach, as demonstrated in preclinical and clinical models. Here we provide a historical summary of the discovery of BAs and their receptors, as well as a summary on the role of BA signalling in the control of energy homeostasis., Perino and Schoonjans summarize the most recent literature on the receptor-mediated role of bile acid signalling in the control of peripheral and central energy homeostasis.
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- 2022
39. Prevalence and Predictors of Nonalcoholic Fatty Liver Disease in Family Members of Patients With Nonalcoholic Fatty Liver Disease
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Anshuman Elhence, Ramesh Kumar, Abhinav Anand, Deepak Gunjan, Sagnik Biswas, Amit Anurag Singh, Shivanand Gamanagatti, Baibaswata Nayak, Shalimar, and Manas Vaishnav
- Subjects
medicine.medical_specialty ,Hepatology ,Receiver operating characteristic ,business.industry ,Fatty liver ,nutritional and metabolic diseases ,Disease ,medicine.disease ,Chronic liver disease ,digestive system ,digestive system diseases ,Confidence interval ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Original Article ,Observational study ,business ,Body mass index - Abstract
BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide. Despite the high prevalence, no screening recommendations yet exist. We designed a prospective observational study to estimate the prevalence of NAFLD in the family of patients with NAFLD and develop a predictive model for identifying it. METHODOLOGY: The prevalence of NAFLD in patients’ family members was estimated using ultrasonography, and univariate and multivariate odds were calculated for its predictors. A model was created using the significant parameters on multivariate odds, and its performance was tested using the area under the receiver operating characteristic (AUROC). RESULTS: Among 447 family members of 191 patients with NAFLD, the prevalence of NAFLD was 55.9%. Family members with NAFLD were younger and had lower serum levels of aspartate aminotransferase, alanine aminotransferase (ALT), triglycerides. The liver stiffness measurement and controlled attenuation parameter values were also lesser in family members compared to the index cases. Age, body mass index (BMI), and ALT were independent predictors of NAFLD in the family members. A model combining age and BMI had an AUROC of 0.838 [95% confidence interval (CI) 0.800–0.876, P < 0.001]. Age ≥30 years and BMI ≥25 kg/m(2) had an odds ratio of 33.5 (95% CI 17.0–66.0, P < 0.001) for prediction of NAFLD, in comparison to BMI
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- 2022
40. Diabetes Mellitus Increases the Risk of Significant Hepatic Fibrosis in Patients With Non-alcoholic Fatty Liver Disease
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Amninder Kaur, Namita Bansal, Varun Mehta, Arshdeep Singh, Sukhraj P. Singh, Ajit Sood, and Sandeep Chhabra
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medicine.medical_specialty ,Hepatology ,business.industry ,Fatty liver ,Disease ,medicine.disease ,Gastroenterology ,Liver disease ,Fibrosis ,Diabetes mellitus ,Internal medicine ,medicine ,Original Article ,In patient ,Transient elastography ,Hepatic fibrosis ,business - Abstract
BACKGROUND: Diabetes mellitus is associated with an increased risk of development of non-alcoholic fatty liver disease (NAFLD). However, the risk posed by diabetes mellitus in progression of liver disease is uncertain. This study compared the severity of hepatic fibrosis in patients with NAFLD with and without diabetes mellitus. METHODS: Consecutive adult patients with NAFLD undergoing transient elastography [FibroScan Touch 502 (Echosens, Paris, France)] at a tertiary care center in north India were analyzed for severity of hepatic fibrosis. The aspartate aminotransferase (AST) to platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4), and NAFLD Fibrosis Score (NFS) were calculated. The degree of hepatic fibrosis as determined by FibroScan and non-invasive serum fibrosis models in patients with and without diabetes mellitus were compared. RESULTS: A total of two hundred patients [118 (59%) males, mean age 50.30 ± 11.13 years] were enrolled. Significant hepatic fibrosis was present in 86 (43%) patients [mean age 50.66 ± 10.96 years, 56 (65.11%) males]. The mean FibroScan, APRI, FIB-4, and NFS scores were 9.86 ± 2.97, 0.75 ± 0.47, 2.41 ± 1.41 and −0.24 ± 1.43 in patients with diabetes compared to 5.31 ± 1.09, 0.49 ± 0.27, 1.55 ± 0.85, and −2.12 ± 1.88 in patients without diabetes, respectively (P=
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- 2022
41. Spontaneous Rupture of Hepatocellular Carcinoma: New Insights
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Linda L. Wong and Adham E. Obeidat
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medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Incidence (epidemiology) ,Fatty liver ,Disease ,medicine.disease ,Gastroenterology ,digestive system diseases ,03 medical and health sciences ,0302 clinical medicine ,Tumor progression ,030220 oncology & carcinogenesis ,Internal medicine ,Hepatocellular carcinoma ,Medicine ,Original Article ,030211 gastroenterology & hepatology ,business ,Complication ,Cause of death - Abstract
Background Spontaneous rupture of hepatocellular carcinoma (HCC) is a potentially fatal complication and the third leading cause of death in patients with HCC after tumor progression and liver failure. Previous studies suggested that improved HCC surveillance has decreased the incidence of rupture. This study aims to characterize patients with ruptured HCC over time and identify predictors of rupture. Methods We retrospectively reviewed a prospectively collected database of 1451 HCC patients to identify cases with rupture and predictors of rupture. Data were divided into three 9-year eras to compare and trend patient/tumor characteristics and rupture. Results Fifty-seven patients (3.9%) presented with spontaneous HCC rupture and the following characteristics: mean age 62.6 years, 73.7% males, 41% cirrhosis, and mean tumor size of 8.0 cm. On multivariate analyses, predictors of rupture included obesity, tumor >5 cm, and single tumors, whereas the presence of cirrhosis was a negative predictor for rupture. Across three eras, there were changes in disease etiology and decreases in tumor size, and more HCCs were found with surveillance. However, more patients were noncirrhotic, and the incidence of spontaneous rupture was unchanged over time. Conclusion Despite improved early detection of HCC over time, the incidence of rupture has been unchanged. The persistent incidence of rupture may possibly be attributed to increasing proportion of fatty liver–related HCC patients who lack traditional risk factors for surveillance and may not have cirrhosis. Better identification of fatty liver disease and determining which patients need HCC surveillance may be needed in the future to prevent spontaneous rupture.
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- 2022
42. Prevalence and predictors of non-alcoholic steatohepatitis in patients with morbid obesity
- Author
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Ramón Corripio, Antonio Olveira, Isabel Calvo-Viñuelas, Miriam Romero, Lucrecia Herranz, Ana Isabel de-Cos-Blanco, David Vicent, Diego Meneses, and María del Carmen Méndez
- Subjects
medicine.medical_specialty ,Biopsy ,Endocrinology, Diabetes and Metabolism ,Bariatric Surgery ,digestive system ,Gastroenterology ,Endocrinology ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Prevalence ,medicine ,Humans ,Nutrition and Dietetics ,medicine.diagnostic_test ,Receiver operating characteristic ,biology ,business.industry ,Fatty liver ,nutritional and metabolic diseases ,Anthropometry ,medicine.disease ,digestive system diseases ,Obesity, Morbid ,Alanine transaminase ,Liver biopsy ,Cohort ,biology.protein ,Steatohepatitis ,business - Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in morbid obesity (MO). A considerable proportion of patients with MO have non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is the only procedure that reliably differentiates NASH from other stages of NAFLD, but its invasive nature prevents it from being generalisable. Hence, non-invasive assessment is critical in this group of patients. Objectives To report NAFLD/NASH prevalence in a cohort of patients with MO and to identify predictors of NASH. Methods Fifty-two consecutive patients subjected to bariatric surgery in a University hospital in Spain underwent LB. Anthropometric, clinical and biochemical variables were registered. According of the results of the LB, individuals were classified by whether they had NASH or not. Multiple logistic regression analysis was performed to identify independent factors associated with NASH. Results NAFLD was reported in 94.2% of the patients, simple steatosis was present in 51.92% and NASH in 42.31%. Meanwhile, 17.3% of patients exhibited significant fibrosis (≥F2). HIGHT score for NASH risk was established using five independent predictors: systemic Hypertension, Insulin resistance, Gamma-glutamyl transferase, High density lipoprotein cholesterol and alanine Transaminase. This score ranges from 0 to 7 and was used to predict NASH in our cohort (area under the receiver operator characteristic curve 0.846). A score of 4 or greater implied high risk (sensitivity 77.3%, specificity 73.3%, positive predictive value 68%, negative predictive value 81.5%, accuracy 75%). Conclusions NAFLD is practically a constant in MO with a considerable proportion of patients presenting NASH. The combination of five independent predictors in a scoring system may help the clinician optimise the selection of patients with MO for LB.
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- 2022
43. Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Adults
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Jiaye Liu, Xiaofang Zhang, Ibrahim Ayada, Maikel P. Peppelenbosch, Ling Wang, Robert J. de Knegt, Zhihui Li, Zhongren Ma, Yang Li, Tianfu Wen, Marco J. Bruno, Qiuwei Pan, Wanlu Cao, Mohsen Ghanbari, Gastroenterology & Hepatology, and Epidemiology
- Subjects
Adult ,Male ,medicine.medical_specialty ,Population ,Prevalence ,Overweight ,SDG 3 - Good Health and Well-being ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Epidemiology ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Obesity ,education ,education.field_of_study ,Hepatology ,business.industry ,Fatty liver ,Gastroenterology ,medicine.disease ,Diabetes Mellitus, Type 2 ,Female ,Metabolic syndrome ,medicine.symptom ,business ,Body mass index - Abstract
Background & Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). In this study, we aim to estimate the global prevalence of MAFLD specifically in overweight and obese adults from the general population by performing a systematic review and meta-analysis through mining the existing epidemiological data on fatty liver disease. Methods: We searched Medline, Embase, Web of Science, Cochrane and google scholar database from inception to November, 2020. DerSimonian-Laird random-effects model with Logit transformation was performed for data analysis. Sensitivity analysis and meta-regression were used to explore predictors of MAFLD prevalence in pooled statistics with high heterogeneity. Results: We identified 116 relevant studies comprised of 2,667,052 participants in general population with an estimated global MAFLD prevalence as 50.7% (95% CI 46.9-54.4) among overweight/obese adults regardless of diagnostic techniques. Ultrasound was the most commonly used diagnostic technique generating prevalence rate of 51.3% (95% CI, 49.1-53.4). Male (59.0%; 95% CI, 52.0-65.6) had a significantly higher MAFLD prevalence than female (47.5%; 95% CI, 40.7-54.5). Interestingly, MAFLD prevalence rates are comparable based on classical NAFLD and non-NAFLD studies in general population. The pooled estimate prevalence of comorbidities such as type 2 diabetes and metabolic syndrome was 19.7% (95% CI, 12.8-29.0) and 57.5% (95% CI, 49.9-64.8), respectively. Conclusions: MAFLD has an astonishingly high prevalence rate in overweight and obese adults. This calls for attention and dedicated action from primary care physicians, specialists, health policy makers and the general public alike.
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- 2022
44. Association Between Non-Alcoholic Fatty Liver Disease and Diabetes-Related Microvascular Complications: A Retrospective Cross-Sectional Study of Hospitalized Patients
- Author
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Jiayu Cheng, Linong Ji, Da Chen, Xin Wen, and Xianghai Zhou
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Diabetic neuropathy ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Prevalence ,medicine ,Humans ,Diabetic Nephropathies ,030212 general & internal medicine ,Retrospective Studies ,business.industry ,Fatty liver ,nutritional and metabolic diseases ,General Medicine ,Diabetic retinopathy ,Odds ratio ,medicine.disease ,digestive system diseases ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,business ,Body mass index - Abstract
Objective Owing to limited research, the effect of non-alcoholic fatty liver disease (NAFLD) on type 2 diabetes outcomes remains unclear. This study aimed to investigate the association between NAFLD and microvascular complications in hospitalized patients with type 2 diabetes. Methods We included 1982 patients with type 2 diabetes. NAFLD was defined as hepatic steatosis detected by ultrasound without secondary causes of fat accumulation. The diagnosis of diabetic retinopathy (DR), diabetic kidney disease (DKD) and diabetic neuropathy was based on clinical medical records. Risk for advanced liver fibrosis was categorized as “low risk,” “indeterminate risk,” and “high risk,” based on the NAFLD Fibrosis Score (NAFLD-FS). Logistic regression was used to test the association between NAFLD, risk for advanced fibrosis and the presence of DR, DKD, and diabetic neuropathy. Results The prevalence of NAFLD was 61.3%. The presence of DR (odds ratio [OR]: 0.749, 95% confidence interval [CI]: 0.578–0.971), and DKD (OR: 0.667, 95% CI: 0.515–0.864) was inversely associated with NAFLD, after adjusting for covariates. The presence of DR and DKD was higher in the “indeterminate risk” (DR: OR: 1.237, 95% CI: 0.730–2.096; DKD: OR: 1.009, 95% CI: 0.640–1.591, respectively) and “high risk” group (DR: OR: 1.341, 95% CI: 0.730–2.463; DKD: OR: 1.732, 95% CI: 1.021–2.940, respectively) than in the “low risk” group, after adjusting for the same covariates. Only the presence of DKD significantly increased with high NAFLD-FS (P=0.01 for trend). Conclusion The presence of DR and DKD was inversely associated with NAFLD among hospitalized patients with type 2 diabetes. DKD was closely associated with high NAFLD-FS among patients with NAFLD.
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- 2022
45. Diagnostic Value of Acyl-Ghrelin in Type 2 Diabetic Patients with Non-alcoholic Fatty Liver Disease
- Author
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Motaz Mohammed Sayed, Elham Mohamed Youssef, Diaa El-Din Mohammad Soliman El-Beik, Azza Emam Mohamed, Wafaa M. Ezzat, Omneya Moguib, Reham Ibrahim Siddik Aly, Essam Mohammed Bayoumy, and Mohamed Ossama Ali
- Subjects
medicine.medical_specialty ,business.industry ,Fatty liver ,nutritional and metabolic diseases ,Non alcoholic ,General Medicine ,Disease ,medicine.disease ,Endocrinology ,Internal medicine ,medicine ,Acyl ghrelin ,business ,Value (mathematics) - Abstract
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Type 2 diabetes (T2D) is described as one of the most significant risk factor for developing NAFLD, non-alcoholic steatohepatitis, and advanced cirrhosis. Liver biopsy cannot be used routinely to diagnose NAFLD. Therefore, it is critically urgent to develop a simple non-invasive test. AIM: This study examined fasting Acyl-Ghrelin (AG) as a non-invasive biomarker to accurately diagnose NAFLD in diabetic patients. PATIENTS AND METHODS: Sixty-one patients with T2D were divided into a test group with NAFLD, and a control group without NAFLD. Secondary causes of fatty liver, chronic viral hepatitis, and drug-induced liver damage were excluded from the study. Anthropometric measurements, lipid profile, fasting blood sugar (FBS), liver enzyme activities, and fasting AG levels were collected. Data management and analysis were performed using statistical package for social sciences version 20. RESULTS: Fasting AG level (pg/ml) in the test group (56.1 ± 10.7) was increased, but not statically significant compared with the control group (37.8 ± 9.3), p > 0.05. However, significant metabolic changes were observed in body weight, waist circumference, FBS, alanine transaminase, and aspartate transaminase between test and control groups. The mean values in the test group are 93.2 ± 14.5, 115.4 ± 7.6, 144.2 ± 25.9, 21.1 ± 5.7, and 32.3 ± 2.1. While the mean values are 87.7 ± 7.3, 95 ± 3.8, 123.7 ± 20.7, 18.6 ± 5, and 20 ± 7, respectively, in the control group. CONCLUSIONS: While elevated AG levels alone were not significant, elevated AG levels plus other parameters of liver damage and obesity were associated with the diagnosis of NAFLD. However, more studies are needed to consider elevated AG as a diagnostic marker in NAFLD patients with T2D.
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- 2022
46. Endoscopic Bariatric Interventions in Patients with Chronic Liver Disease
- Author
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Marco Bustamante-Bernal, Marc J. Zuckerman, and Luis O. Chavez
- Subjects
medicine.medical_specialty ,Gastroplasty ,medicine.medical_treatment ,Population ,Psychological intervention ,Bariatric Surgery ,Disease ,Liver transplantation ,Chronic liver disease ,Gastroenterology ,Bariatrics ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,Humans ,Medicine ,Obesity ,education ,education.field_of_study ,Hepatology ,business.industry ,Fatty liver ,Endoscopy ,medicine.disease ,Treatment Outcome ,business - Abstract
Obesity and its associated comorbidities are rapidly increasing in the US population. Therefore, metabolic associated fatty liver disease (MAFLD), previously known as nonalcoholic fatty liver disease (NAFLD), has become a leading indication for liver transplantation. Lifestyle modifications as a sole therapy have been insufficient to reduce the burden of chronic liver disease secondary to MAFLD. Endoscopic bariatric interventions (EBI) appear to be safe and effective therapies for obesity and chronic liver disease secondary to MAFLD. Gastric EBI include endoscopic sleeve gastroplasty (ESG) and intragastric balloons (IGB). Small bowel EBI are also evolving in the field of bariatric endoscopy.
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- 2022
47. NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options
- Author
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Peter R. Galle, Simon Johannes Gairing, Lukas Müller, and Friedrich Foerster
- Subjects
Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Disease ,Type 2 diabetes ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Internal medicine ,medicine ,Humans ,neoplasms ,Hepatology ,business.industry ,Liver Neoplasms ,Fatty liver ,medicine.disease ,digestive system diseases ,Liver Transplantation ,Clinical trial ,Treatment Outcome ,Liver ,Hepatocellular carcinoma ,Disease Progression ,Metabolic syndrome ,Steatohepatitis ,business - Abstract
In light of a global rise in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) represent an increasingly important underlying aetiology of hepatocellular carcinoma (HCC). HCCs arising from lipotoxicity-mediated chronic inflammation are characterised by several unique features: in contrast to virally driven HCC, up to 50% of NAFLD-HCC occurs in patients without cirrhosis and annual HCC incidence is comparatively low, complicating current surveillance strategies. On average, patients are older and are more frequently diagnosed at an advanced stage. While locoregional treatments are probably equally effective regardless of HCC aetiology, the picture is less clear for systemic therapy. Tyrosine kinase inhibitors are probably equally effective, while there have been initial signals that immune checkpoint inhibitors may be less effective in NAFLD-HCC than in viral HCC. Current international clinical practice guidelines for HCC do not consider aetiology, as there are insufficient data to draw specific conclusions or to recommend aetiology-specific modifications to the current management of patients with HCC. However, in light of the growing relevance of NAFLD-HCC, future clinical trials should assess whether HCC aetiology - and NAFLD/NASH in particular - influence the safety and efficacy of a given treatment.
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- 2022
48. Cardiometabolic Health Outcomes Associated With Discordant Visceral and Liver Fat Phenotypes: Insights From the Dallas Heart Study and UK Biobank
- Author
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Cody McCoy, Tiffany M. Powell-Wiley, Mikael Petersson, Jennifer Linge, Ian J. Neeland, Magnus Borga, Olof Dahlqvist Leinhard, Sanaa Tejani, Jean-Pierre Després, and Colby Ayers
- Subjects
Adult ,Male ,medicine.medical_specialty ,Disease ,Intra-Abdominal Fat ,Endocrinology and Diabetes ,Article ,Body Mass Index ,chemistry.chemical_compound ,High-density lipoprotein ,Risk Factors ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Cardiac and Cardiovascular Systems ,Kardiologi ,business.industry ,Medicinsk bildbehandling ,Hazard ratio ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,United Kingdom ,Confidence interval ,Fatty Liver ,Medical Image Processing ,Phenotype ,Diabetes Mellitus, Type 2 ,chemistry ,Cardiovascular Diseases ,Endokrinologi och diabetes ,Female ,Radiologi och bildbehandling ,business ,Body mass index ,Radiology, Nuclear Medicine and Medical Imaging - Abstract
Objective: To evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts. Patients and Methods: Participants in the Dallas Heart Study underwent baseline imaging from January 1, 2000, through December 31, 2002, and were followed for incident cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) through 2013. Associations between VAT-LF groups (low-low, high-low, low-high, and high-high) and outcomes were assessed using multivariable- adjusted regression and were replicated in the independent UK Biobank. Results: The Dallas Heart Study included 2064 participants (mean SD age, 449 years; 54% female; 47% black). High VATehigh LF and high VATelow LF were associated with prevalent atheroscle- rosis, whereas low VATehigh LF was not. Of 1731 participants without CVD/T2DM, 128 (7.4%) developed CVD and 95 (5.5%) T2DM over a median of 12 years. High VATehigh LF and high VATelow LF were associated with increased risk of CVD (hazard ratios [HRs], 2.0 [95% CI, 1.3 to 3.2] and 2.4 [95% CI, 1.4 to 4.1], respectively) and T2DM (odds ratios [ORs], 7.8 [95% CI, 3.8 to 15.8] and 3.3 [95% CI, 1.4 to 7.8], respectively), whereas low VATehigh LF was associated with T2DM (OR, 2.7 [95% CI, 1.1 to 6.7]). In the UK Biobank (N1⁄422,354; April 2014-May 2020), only high VATelow LF remained associated with CVD after multivariable adjustment for age and body mass index (HR, 1.5 [95% CI, 1.2 to 1.9]). Conclusion: Although VAT and LF are each associated with cardiometabolic risk, these observations demonstrate the importance of separating their cardiometabolic implications when there is presence or absence of either or both in an individual. Funding: National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK106520]; National Center for Advancing Translational Sciences [UL1TR001105]; Swedish Research Council [VR-2019-04751]
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- 2022
49. Pharmacologic IRE1/XBP1s activation promotes systemic adaptive remodeling in obesity
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Julia M. D. Grandjean, Verena Albert, Andrea Galmozzi, R. Luke Wiseman, Ara Sukiasyan, Enrique Saez, Bernard P. Kok, Aparajita Madhavan, Bibiana Rius, and Evan T. Powers
- Subjects
X-Box Binding Protein 1 ,medicine.medical_specialty ,medicine.medical_treatment ,Science ,General Physics and Astronomy ,Mice, Obese ,Inflammation ,Protein Serine-Threonine Kinases ,Carbohydrate metabolism ,General Biochemistry, Genetics and Molecular Biology ,Article ,Stress signalling ,Mice ,Fibrosis ,Internal medicine ,medicine ,Animals ,Homeostasis ,Obesity ,Transcription factor ,Multidisciplinary ,Molecular medicine ,business.industry ,Insulin ,Membrane Proteins ,General Chemistry ,medicine.disease ,Fatty Liver ,Glucose ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,Liver ,Unfolded Protein Response ,medicine.symptom ,Steatosis ,business ,Pancreas ,Signal Transduction ,Transcription Factors - Abstract
In obesity, signaling through the IRE1 arm of the unfolded protein response exerts both protective and harmful effects. Overexpression of the IRE1-regulated transcription factor XBP1s in liver or fat protects against obesity-linked metabolic deterioration. However, hyperactivation of IRE1 engages regulated IRE1-dependent decay (RIDD) and TRAF2/JNK pro-inflammatory signaling, which accelerate metabolic dysfunction. These pathologic IRE1-regulated processes have hindered efforts to pharmacologically harness the protective benefits of IRE1/XBP1s signaling in obesity-linked conditions. Here, we report the effects of a XBP1s-selective pharmacological IRE1 activator, IXA4, in diet-induced obese (DIO) mice. IXA4 transiently activates protective IRE1/XBP1s signaling in liver without inducing RIDD or TRAF2/JNK signaling. IXA4 treatment improves systemic glucose metabolism and liver insulin action through IRE1-dependent remodeling of the hepatic transcriptome that reduces glucose production and steatosis. IXA4-stimulated IRE1 activation also enhances pancreatic function. Our findings indicate that systemic, transient activation of IRE1/XBP1s signaling engenders multi-tissue benefits that integrate to mitigate obesity-driven metabolic dysfunction., Signalling through the IRE1 arm of the unfolded protein response exerts both protective and harmful effects in obesity. Here the authors report that a selective pharmacologic activator of IRE1/XBP1s signalling stimulates an adaptive remodelling of liver and pancreas in diet-induced obese mice and mitigates obesity-linked systemic metabolic dysfunction.
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- 2022
50. Metabolic associated fatty liver disease is a risk factor for chronic kidney disease
- Author
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Michiaki Fukui, Takao Kojima, Takuro Okamura, Naoko Nakanishi, Akihiro Obora, Yoshitaka Hashimoto, and Masahide Hamaguchi
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Renal function ,Gastroenterology ,Diseases of the endocrine glands. Clinical endocrinology ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Fatty liver ,Internal Medicine ,medicine ,Humans ,Obesity ,Renal Insufficiency, Chronic ,Risk factor ,Retrospective Studies ,business.industry ,Hazard ratio ,fungi ,Diabetes ,General Medicine ,Odds ratio ,Kidney disease ,medicine.disease ,RC648-665 ,Metabolic syndrome ,Cross-Sectional Studies ,business - Abstract
Background and Aims To clarify the relationship between metabolic dysfunction‐associated fatty liver disease (MAFLD) and chronic kidney disease (CKD). Methods The participants were divided into four groups by the presence or absence of fatty liver disease (FLD) and metabolic dysfunction (MD). MAFLD was defined as having both FLD and MD, whereas CKD was defined as having an estimated glomerular filtration rate of
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- 2022
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