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Tamini S, Bondesan A, Caroli D, Marazzi N, Sartorio A. The Ability of the Triglyceride-Glucose (TyG) Index and Modified TyG Indexes to Predict the Presence of Metabolic-Associated Fatty Liver Disease and Metabolic Syndrome in a Pediatric Population with Obesity. J Clin Med 2025; 14:2341. [PMID: 40217790 PMCID: PMC11989838 DOI: 10.3390/jcm14072341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 03/25/2025] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
Background: Metabolic-associated fatty liver disease (MASLD) and metabolic syndrome (MetS) are increasingly prevalent among children and adolescents with obesity, posing significant long-term metabolic and cardiovascular risks. Non-invasive identification of at-risk individuals is crucial for a timely intervention. This study aimed to evaluate the diagnostic performance of the triglyceride-glucose (TyG) index and its modified versions, TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC), in predicting MASLD and MetS in a large cohort of children and adolescents with obesity. Methods: A total of 758 children and adolescents with obesity (454 females, 304 males; mean age 14.8 ± 2.1 years; mean BMI 37.9 ± 6.2 kg/m2) were included. MASLD was diagnosed via ultrasonography, while MetS was defined using International Diabetes Federation criteria. TyG, TyG-WC, and TyG-BMI were calculated for all participants. Receiver operating characteristic (ROC) curves were generated to assess the diagnostic accuracy of these indexes, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: MASLD was detected in 38.9% of participants, with a higher prevalence in males (p < 0.0001). MetS was present in 27.8% of the cohort, with higher prevalence in males (p < 0.0001). Among the indexes, TyG-WC exhibited the highest sensitivity for MASLD (77.6%), whereas TyG-BMI had the highest specificity (63.3%). In predicting MetS, all three indexes performed better than for MASLD, with TyG demonstrating the highest PPV (54.5%) and TyG-BMI the highest NPV (87.5%). Predictive performance was lower in males than females, potentially due to sex-specific differences in fat distribution and metabolic response. Conclusions: TyG, TyG-WC, and TyG-BMI are promising, non-invasive tools for identifying children and adolescents with obesity at risk for MASLD and MetS. The superior sensitivity of TyG-WC and the high specificity of TyG-BMI highlight the value of incorporating anthropometric parameters into metabolic screening. Integrating these indexes into routine clinical practice may enhance early detection, allowing for timely intervention and personalized management strategies, ultimately reducing the long-term burden of metabolic and liver diseases in pediatric populations.
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Affiliation(s)
- Sofia Tamini
- Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Experimental Laboratory for Auxo-Endocrinological Research, 28824 Piancavallo-Verbania, Italy; (A.B.); (D.C.); (N.M.); (A.S.)
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Sabini JH, Timotius KH. Hepatoprotective and Fat-Accumulation-Reductive Effects of Curcumin on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Curr Issues Mol Biol 2025; 47:159. [PMID: 40136412 PMCID: PMC11940900 DOI: 10.3390/cimb47030159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 02/06/2025] [Accepted: 02/25/2025] [Indexed: 03/27/2025] Open
Abstract
Fat accumulation is the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD). Given the intimidating nature of its treatment, curcumin (CUR) emerges as a potential therapeutic agent due to its proven effectiveness in managing MASLD. This review aimed to evaluate previous reports on the hepatoprotective and fat-accumulation-reductive effects of CUR administration in preventing or treating MASLD. CUR administration can modulate serum liver enzymes and lipid profiles. The fat accumulation of MASLD is the primary cause of oxidative stress and inflammation. By reducing fat accumulation, CUR may attenuate the inflammation and oxidative stress in MASLD. In addition, CUR has been proven to restore the dysfunctional cellular energy metabolism capacity and attenuate fibrogenesis (antifibrotic agent). Their hepatoprotective effects are associated with fat accumulation in MASLD. Lipid metabolism (lipogenesis, lipolysis, and lipophagy) is correlated with their hepatoprotective effects. CUR has prophylactic and therapeutic effects, particularly in early-stage MASLD, primarily when it is used as a fat reducer. It can be considered an excellent natural therapeutic drug for MASLD because it protects the liver and attenuates fat accumulation, especially in the early stage of MASLD development.
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Affiliation(s)
| | - Kris Herawan Timotius
- Faculty of Medicine and Health Sciences, Krida Wacana Christian University, Jakarta 11510, Indonesia;
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Chen S, Huang W, Huang T, Fang C, Zhao K, Zhang Y, Li H, Wu C. Highly sensitive near-infrared fluorescent probe for monitoring peroxynitrite in nonalcoholic fatty liver disease: Toward early diagnosis and therapeutic evaluation. Talanta 2025; 281:126865. [PMID: 39265422 DOI: 10.1016/j.talanta.2024.126865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 08/31/2024] [Accepted: 09/08/2024] [Indexed: 09/14/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD) poses a significant global health concern, necessitating precise diagnostic tools and effective treatment strategies. Peroxynitrite (ONOO-), a reactive oxygen species, plays a pivotal role in NAFLD pathogenesis, highlighting its potential as a biomarker for disease diagnosis and therapeutic evaluation. This study reports on the development of a near-infrared (NIR) fluorescent probe, designated DRP-O, for the selective detection of ONOO- with high sensitivity and photostability. DRP-O exhibits rapid response kinetics (within 2 min) and an impressive detection limit of 2.3 nM, enabling real-time monitoring of ONOO- dynamics in living cells. Notably, DRP-O demonstrates excellent photostability under continuous laser irradiation, ensuring reliable long-term monitoring in complex biological systems. We apply DRP-O to visualize endogenous ONOO- in living cells, demonstrating its potential for diagnosing and monitoring NAFLD-related oxidative stress. Furthermore, DRP-O effectively evaluates the efficacy of therapeutic drugs in NAFLD cell models, underscoring its potential utility in drug screening studies. Moreover, we confirm DRP-O to enable selective identification of fatty liver tissues in a mouse model of NAFLD, indicating its potential for the early diagnosis of NAFLD. Collectively, DRP-O represents a valuable tool for studying ONOO- dynamics, evaluating drug efficacy, and diagnosing NAFLD, offering insights into novel therapeutic strategies for this prevalent liver disorder.
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Affiliation(s)
- Shiying Chen
- School of Materials and Chemical Engineering, Ningbo University of Technology, Ningbo, 315211, PR China; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China
| | - Wei Huang
- School of Materials and Chemical Engineering, Ningbo University of Technology, Ningbo, 315211, PR China; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China
| | - Ting Huang
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China
| | - Cong Fang
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China
| | - Kuicheng Zhao
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China
| | - Youyu Zhang
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China
| | - Haitao Li
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China
| | - Cuiyan Wu
- School of Materials and Chemical Engineering, Ningbo University of Technology, Ningbo, 315211, PR China; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China.
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Zhang Q, Huang Y, Gao S, Ding Y, Zhang H, Chang G, Wang X. Obesity-Related Ciliopathies: Focus on Advances of Biomarkers. Int J Mol Sci 2024; 25:8484. [PMID: 39126056 PMCID: PMC11312664 DOI: 10.3390/ijms25158484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 07/27/2024] [Accepted: 08/01/2024] [Indexed: 08/12/2024] Open
Abstract
Obesity-related ciliopathies, as a group of ciliopathies including Alström Syndrome and Bardet-Biedl Syndrome, exhibit distinct genetic and phenotypic variability. The understanding of these diseases is highly significant for understanding the functions of primary cilia in the human body, particularly regarding the relationship between obesity and primary cilia. The diagnosis of these diseases primarily relies on clinical presentation and genetic testing. However, there is a significant lack of research on biomarkers to elucidate the variability in clinical manifestations, disease progression, prognosis, and treatment responses. Through an extensive literature review, the paper focuses on obesity-related ciliopathies, reviewing the advancements in the field and highlighting the potential roles of biomarkers in the clinical presentation, diagnosis, and prognosis of these diseases.
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Affiliation(s)
- Qianwen Zhang
- Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; (Q.Z.); (Y.H.); (S.G.); (Y.D.)
| | - Yiguo Huang
- Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; (Q.Z.); (Y.H.); (S.G.); (Y.D.)
| | - Shiyang Gao
- Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; (Q.Z.); (Y.H.); (S.G.); (Y.D.)
| | - Yu Ding
- Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; (Q.Z.); (Y.H.); (S.G.); (Y.D.)
| | - Hao Zhang
- Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children’s Medical Center, National Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China;
| | - Guoying Chang
- Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; (Q.Z.); (Y.H.); (S.G.); (Y.D.)
| | - Xiumin Wang
- Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; (Q.Z.); (Y.H.); (S.G.); (Y.D.)
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Nurhayati T, Ridho MF, Santoso PTR, Setiawan S, Goenawan H, Tarawan VM. Effects of Moringa oleifera Leaf Extract on Liver Histopathology: A Systematic Review. J Nutr Metab 2024; 2024:6815993. [PMID: 38993633 PMCID: PMC11239234 DOI: 10.1155/2024/6815993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 06/10/2024] [Accepted: 06/20/2024] [Indexed: 07/13/2024] Open
Abstract
Introduction Moringa leaves (Moringa oleifera), which are members of the Moringaceae family, are one of the herbal plants that are widely known in Indonesia. Phytochemical contents of moringa leaf, such as flavonoid, quercetin, and phenolic acid, are believed to have an effect on improvement of NAFLD. Therefore, moringa leaf is considered as one the herbal plants that can be used as supplementation in the form of adjuvant therapy to NAFLD. The study objective of our research is to review the effect of giving moringa leaf to the liver, especially the histopathologic features. This study will be conducted on literature review research design, more specifically in the form of a systematic review. Research Method. Five major electronic web databases, including PubMed, Cochrane Library, Google Scholar, Scopus, and ScienceDirect, were used in identifying literature from 2014 to 2023. Results From a comprehensive analysis of 13 relevant literature sources, we elucidate the impact of Moringa oleifera leaf extract on liver histopathology, glucose, and lipid metabolism. Furthermore, we provide insights into its safety profile concerning human health. Conclusion The phytochemical content of Moringa oleifera leaf extract had shown a significant benefit in plant medicinal sector. From the research that had been done, Moringa oleifera leaf extract contributes to give significant improvement on liver histopathological features, glucose, and lipid metabolism on animal sample model.
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Affiliation(s)
- Titing Nurhayati
- Department of Biomedical ScienceFaculty of MedicinePadjadjaran University, Bandung, Indonesia
- Faculty of MedicinePadjadjaran University, Bandung, Indonesia
| | | | | | - Setiawan Setiawan
- Department of Biomedical ScienceFaculty of MedicinePadjadjaran University, Bandung, Indonesia
| | - Hanna Goenawan
- Department of Biomedical ScienceFaculty of MedicinePadjadjaran University, Bandung, Indonesia
| | - Vita Murniati Tarawan
- Department of Biomedical ScienceFaculty of MedicinePadjadjaran University, Bandung, Indonesia
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Campsen J, Poole C. CT-Based Hounsfield Units for Pre-donation Liver Steatosis Assessment: Enhancing Transplant Outcomes and Efficiency. Cureus 2024; 16:e61196. [PMID: 38939256 PMCID: PMC11208326 DOI: 10.7759/cureus.61196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/27/2024] [Indexed: 06/29/2024] Open
Abstract
Steatotic liver grafts are associated with increased post-transplant complications and graft failure. The field of transplantation faces a challenge in the absence of a reliable pre-donation protocol for quantitatively assessing steatosis in cadaveric liver grafts. Current pre-donation evaluation protocols often involve non-contrast computed tomography (CT) scans of the chest and/or abdomen as an initial step in organ donation assessment. These routine scans have the potential to identify and quantify hepatic fat content when more than 20% of the liver parenchyma is affected. By incorporating both abdominal and thoracic CT scans during the donor workup, an assessment of the quality of the liver and spleen can be achieved. Our study is based on the hypothesis that a precise pre-donation evaluation utilizing Hounsfield units (HU) derived from CT images of the liver and spleen can provide transplant programs with crucial data regarding the extent of steatosis. This approach is envisioned as a significant advancement that could potentially eliminate the need for preoperative liver biopsies by offering essential information to streamline the evaluation process.
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Affiliation(s)
- Jeffrey Campsen
- Surgery, University of Utah School of Medicine, Salt Lake City, USA
- Organ Procurement Organization, Donor Connect, Salt Lake City, USA
| | - Carrie Poole
- Organ Procurement Organization, Donor Connect, Salt Lake City, USA
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Sun HJ, Jiao B, Wang Y, Zhang YH, Chen G, Wang ZX, Zhao H, Xie Q, Song XH. Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions. World J Gastroenterol 2024; 30:1968-1981. [PMID: 38681120 PMCID: PMC11045491 DOI: 10.3748/wjg.v30.i14.1968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 02/15/2024] [Accepted: 03/25/2024] [Indexed: 04/12/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease. However, the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies. Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoetiology and suggest functional therapeutic and diagnostic options. Pyroptosis, ferroptosis, and necroptosis are the main subtypes of non-apoptotic regulated cell deaths (RCDs), each of which represents particular characteristics. Considering the complexity of the findings, the present study aimed to review these types of RCDs and their contribution to NAFLD progression, and subsequently discuss in detail the role of necroptosis in the pathoetiology, diagnosis, and treatment of the disease. The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer, hence it has potential in diagnostic and therapeutic approaches. Nevertheless, further studies are necessary.
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Affiliation(s)
- Hong-Ju Sun
- Department of General Medicine, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
| | - Bo Jiao
- Department of General Medicine, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
| | - Yan Wang
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
| | - Yue-Hua Zhang
- Department of Medical Administration, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
| | - Ge Chen
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
- Qingdao Medical College, Qingdao University, Qingdao 266042, Shandong Province, China
| | - Zi-Xuan Wang
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
- Qingdao Medical College, Qingdao University, Qingdao 266042, Shandong Province, China
| | - Hong Zhao
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Xiao-Hua Song
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
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Elfaal M, Supersad A, Ferguson C, Locas S, Manolea F, Wilson MP, Sam M, Tu W, Low G. Two-point Dixon and six-point Dixon magnetic resonance techniques in the detection, quantification and grading of hepatic steatosis. World J Radiol 2023; 15:293-303. [PMID: 37969136 PMCID: PMC10631370 DOI: 10.4329/wjr.v15.i10.293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/20/2023] [Accepted: 09/28/2023] [Indexed: 10/24/2023] Open
Abstract
BACKGROUND Hepatic steatosis is a very common problem worldwide. AIM To assess the performance of two- and six-point Dixon magnetic resonance (MR) techniques in the detection, quantification and grading of hepatic steatosis. METHODS A single-center retrospective study was performed in 62 patients with suspected parenchymal liver disease. MR sequences included two-point Dixon, six-point Dixon, MR spectroscopy (MRS) and MR elastography. Fat fraction (FF) estimates on the Dixon techniques were compared to the MRS-proton density FF (PDFF). Statistical tests used included Pearson's correlation and receiver operating characteristic. RESULTS FF estimates on the Dixon techniques showed excellent correlation (≥ 0.95) with MRS-PDFF, and excellent accuracy [area under the receiver operating characteristic (AUROC) ≥ 0.95] in: (1) Detecting steatosis; and (2) Grading severe steatosis, (P < 0.001). In iron overload, two-point Dixon was not evaluable due to confounding T2* effects. FF estimates on six-point Dixon vs MRS-PDFF showed a moderate correlation (0.82) in iron overload vs an excellent correlation (0.97) without iron overload, (P < 0.03). The accuracy of six-point Dixon in grading mild steatosis improved (AUROC: 0.59 to 0.99) when iron overload cases were excluded. The excellent correlation (> 0.9) between the Dixon techniques vs MRS-PDFF did not change in the presence of liver fibrosis (P < 0.01). CONCLUSION Dixon techniques performed satisfactorily for the evaluation of hepatic steatosis but with exceptions.
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Affiliation(s)
- Mohamed Elfaal
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton T6G2B7, Alberta, Canada
| | - Alanna Supersad
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton T6G2B7, Alberta, Canada
| | - Craig Ferguson
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton T6G2B7, Alberta, Canada
| | - Stephanie Locas
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton T6G2B7, Alberta, Canada
| | - Florin Manolea
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton T6G2B7, Alberta, Canada
| | - Mitchell P Wilson
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton T6G2B7, Alberta, Canada
| | - Medica Sam
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton T6G2B7, Alberta, Canada
| | - Wendy Tu
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton T6G2B7, Alberta, Canada
| | - Gavin Low
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton T6G2B7, Alberta, Canada
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Silva V, Faria HOF, Sousa-Filho CPB, de Alvarenga JFR, Fiamoncini J, Otton R. Thermoneutrality or standard temperature: is there an ideal housing temperature to study the antisteatotic effects of green tea in obese mice? J Nutr Biochem 2023; 120:109411. [PMID: 37423321 DOI: 10.1016/j.jnutbio.2023.109411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 06/15/2023] [Accepted: 06/29/2023] [Indexed: 07/11/2023]
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a condition characterized by excessive accumulation of triglycerides in hepatocytes, currently considered the number one cause of chronic liver disease. MAFLD is strongly associated with obesity, type 2 diabetes, hyperlipidaemia, and hypertension. Emphasis has been placed on the use of green tea (GT), produced from the Camellia sinensis plant, rich in antioxidants as polyphenols and catechins, on obesity and MAFLD treatment/prevention. Studies carried out in rodent models housed at a standard temperature (ST, 22°C) are being questioned as ST is a determining factor on generating changes in the physiology of immune response, and energy metabolism. On the other hand, it seems that thermoneutrality (TN, 28°C) represents a closer parallel to human physiology. In this perspective, we investigated the effects of GT (500 mg/kg of body weight, over 12 weeks, 5 days/week) by comparing mice housed at ST or TN in a model of MAFLD of diet-induced obese males C57Bl/6 mice. We show that the liver phenotype at TN exhibits a more severe MAFLD while GT ameliorates this condition. In parallel, GT restores the expression of genes involved in the lipogenic pathway, regardless of temperature, with slight modifications in lipolysis/fatty acid oxidation. We observed an increase promoted by GT in PPARα and PPARγ proteins independently of housing temperature and a dual pattern of bile acid synthesis. Thus, animals' conditioning temperature is a key factor that can interfere in the results involving obesity and MAFLD, although GT has beneficial effects against MAFLD independently of the housing temperature of mice.
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Affiliation(s)
- Victória Silva
- Interdisciplinary Postgraduate Program in Health Sciences, Cruzeiro do Sul University, Sao Paulo, Sao Paulo, Brazil
| | | | | | - José Fernando Rinaldi de Alvarenga
- Department of Food Science and Experimental Nutrition, Food Research Center, School of Pharmaceutical Sciences, University of São Paulo, Sao Paulo, Sao Paulo, Brazil
| | - Jarlei Fiamoncini
- Department of Food Science and Experimental Nutrition, Food Research Center, School of Pharmaceutical Sciences, University of São Paulo, Sao Paulo, Sao Paulo, Brazil
| | - Rosemari Otton
- Interdisciplinary Postgraduate Program in Health Sciences, Cruzeiro do Sul University, Sao Paulo, Sao Paulo, Brazil.
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Narladkar V, Agrawal A, Bakshi SS, Chakole S, Pathade AG, Yelne S. Unravelling the Interplay: Exploring the Influence of Previous Hepatitis B Virus, Hepatitis A Virus, and Hepatitis E Virus Infections on Non-alcoholic Fatty Liver Disease. Cureus 2023; 15:e44969. [PMID: 37822444 PMCID: PMC10562882 DOI: 10.7759/cureus.44969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 09/09/2023] [Indexed: 10/13/2023] Open
Abstract
The intricate interplay between viral infections and non-alcoholic fatty liver disease (NAFLD) presents a fascinating and clinically significant intersection of virology and hepatology. This review article delves into the complex relationship between hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis E virus (HEV), and NAFLD. It outlines the shared mechanisms linking viral infections to NAFLD development, including their effects on lipid metabolism, immune responses, inflammation, and gut microbiota. The clinical implications of this interplay are explored, including challenges in diagnosis and management and potential therapeutic strategies. The review emphasises the need for a comprehensive understanding of these interactions as they impact disease progression, risk stratification, and treatment decisions. Furthermore, it highlights the importance of integrated approaches and personalised treatment paradigms for optimising patient care. As we navigate this intricate crossroads, the insights gained can reshape our understanding of liver health and contribute to more effective strategies for managing viral infections and NAFLD.
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Affiliation(s)
- Vinay Narladkar
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Aman Agrawal
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sanket S Bakshi
- Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Swarupa Chakole
- Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Aniket G Pathade
- Research and Development, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Seema Yelne
- Nursing, Shalinitai Meghe College of Nursing, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Sharifi S, Bagherniya M, Khoram Z, Ebrahimi Varzaneh A, Atkin SL, Jamialahmadi T, Sahebkar A, Askari G. Efficacy of curcumin plus piperine co-supplementation in moderate-to-high hepatic steatosis: A double-blind, randomized, placebo-controlled clinical trial. Phytother Res 2023. [PMID: 36799355 DOI: 10.1002/ptr.7764] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 12/29/2022] [Accepted: 01/02/2023] [Indexed: 02/18/2023]
Abstract
Non-alcoholic Fatty Liver Disease (NAFLD) is a global health problem that can progress to steatohepatitis and cirrhosis. The aim of this study was to determine the effect of curcumin + piperine on cardiometabolic risk factors, as well as hepatic steatosis and fibrosis in NAFLD patients with moderate-to-high hepatic steatosis. Patients diagnosed with moderate-to-high NAFLD by liver sonography were randomized to either curcumin + piperine (500 mg/day curcumin plus 5 mg/day piperine) for 12 weeks (n = 30) or placebo groups (n = 30). Liver fibroscan, anthropometric measurements, dietary intake, physical activity, blood pressure, lipid profile, high-sensitivity C-reactive protein, fasting blood glucose (FBG), and liver enzymes were assessed at baseline and after 12 weeks of follow-up. Intention-to-treat analysis was undertaken. Curcumin + piperine decreased waist circumference (p = 0.026), systolic blood pressure (p = 0.001), total cholesterol (p = 0.004), low-density lipoprotein-cholesterol (p = 0.006), FBG (p = 0.002), alanine transaminase (p = 0.007) and aspartate transaminase (p = 0.012) compared with placebo. However, fibroscan measurement did not differ between curcumin + piperine and placebo groups (p > 0.05). Fibroscan measurement as a marker of NAFLD improvement did not differ after 12 weeks of curcumin + piperine; however, curcumin + piperine may be considered as an adjunct therapy to improve anthropometric measures, blood pressure, lipid profile, blood glucose, and liver function in NAFLD patients.
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Affiliation(s)
- Shima Sharifi
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Bagherniya
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.,Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ziba Khoram
- Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Stephen L Atkin
- School of Postgraduate Studies and Research, RCSI Medical University of Bahrain, Busaiteen, Bahrain
| | - Tannaz Jamialahmadi
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Medicine, The University of Western Australia, Perth, Australia.,Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gholamreza Askari
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.,Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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12
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Quek J, Chan KE, Wong ZY, Tan C, Tan B, Lim WH, Tan DJH, Tang ASP, Tay P, Xiao J, Yong JN, Zeng RW, Chew NWS, Nah B, Kulkarni A, Siddiqui MS, Dan YY, Wong VWS, Sanyal AJ, Noureddin M, Muthiah M, Ng CH. Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2023; 8:20-30. [PMID: 36400097 DOI: 10.1016/s2468-1253(22)00317-x] [Citation(s) in RCA: 256] [Impact Index Per Article: 128.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 09/16/2022] [Accepted: 09/20/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND The global burden of non-alcoholic fatty liver disease (NAFLD) parallels the increase in obesity rates across the world. Although overweight and obesity status are thought to be an effective indicator for NAFLD screening, the exact prevalence of NAFLD in this population remains unknown. We aimed to report the prevalence of NAFLD, non-alcoholic fatty liver (NAFL), and non-alcoholic steatohepatitis (NASH) in the overweight and obese population. METHODS In this systematic review and meta-analysis, we searched Medline and Embase from database inception until March 6, 2022, using search terms including but not limited to "non-alcoholic fatty liver disease", "overweight", "obesity", and "prevalence". Cross-sectional and longitudinal observational studies published after Jan 1, 2000, written in or translated into English were eligible for inclusion; paediatric studies were excluded. Articles were included if the number of NAFLD, NAFL, or NASH events in an overweight and obese population could be extracted. Summary data were extracted from published reports. The primary outcomes were the prevalence of NAFLD, NAFL, and NASH in an overweight and obese population and the prevalence of fibrosis in individuals who were overweight or obese and who had NAFLD. A meta-analysis of proportions was done with the generalised linear mixed model. This study is registered with PROSPERO (CRD42022344526). FINDINGS The search identified 7389 articles. 151 studies met the inclusion criteria and were included in the meta-analysis. In the pooled analysis comprising 101 028 individuals, the prevalence of NAFLD in the overweight population was 69·99% (95% CI 65·40-74·21 I2=99·10%), the prevalence of NAFL was 42·49% (32·55-53·08, I2=96·40%), and the prevalence of NASH was 33·50% (28·38-39·04, I2=95·60%). Similar prevalence estimates were reported in the obese population for NAFLD (75·27% [95% CI 70·90-79·18]; I2=98·50%), NAFL (43·05% [32·78-53·97]; I2=96·30%) and NASH (33·67% [28·45-39·31]; I2=95·60%). The prevalence of NAFLD in the overweight population was the highest in the region of the Americas (75·34% [95% CI: 67·31-81·93]; I2=99·00%). Clinically significant fibrosis (stages F2-4) was present in 20·27% (95% CI 11·32-33·62; I2= 93·00%) of overweight individuals with NAFLD and in 21·60% (11·47-36·92; I2=95·00%) of obese patients with NAFLD while 6·65% (4·35-10·01; I2=58·00%) of overweight individuals with NAFLD and 6·85% (3·85-11·90; I2=90·00%) of obese individuals with NAFLD had advanced fibrosis (stages F3-4). INTERPRETATION This study summarises the estimated global prevalence of NAFLD, NAFL, and NASH in overweight and obese individuals; these findings are important for improving the understanding of the global NAFLD burden and supporting disease management in the at-risk overweight and obese population. FUNDING None.
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Affiliation(s)
- Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Zhen Yu Wong
- Nottingham City Hospital, Nottingham University Hospitals NHS Trust, United Kingdom
| | - Caitlyn Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Bryan Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ansel Shao Pin Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Phoebe Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | - Nicholas W S Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Benjamin Nah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Anand Kulkarni
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Yock Young Dan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | | | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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13
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Chen B, Tang WHW, Rodriguez M, Corey KE, Sanyal AJ, Kamath PS, Bozkurt B, Virk HUH, Pressman GS, Lazarus JV, El-Serag HB, Krittanawong C. NAFLD in Cardiovascular Diseases: A Contributor or Comorbidity? Semin Liver Dis 2022; 42:465-474. [PMID: 36241194 DOI: 10.1055/s-0042-1757712] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both highly prevalent conditions around the world, and emerging data have shown an association between them. This review found several longitudinal and cross-sectional studies showing that NAFLD was associated with coronary artery disease, cardiac remodeling, aortic valve remodeling, mitral annulus valve calcifications, diabetic cardiomyopathy, diastolic cardiac dysfunction, arrhythmias, and stroke. Although the specific underlying mechanisms are not clear, many hypotheses have been suggested, including that metabolic syndrome might act as an upstream metabolic defect, leading to end-organ manifestations in both the heart and liver. Management of NAFLD includes weight loss through lifestyle interventions or bariatric surgery, and pharmacological interventions, often targeting comorbidities. Although there are no Food and Drug Administration-approved nonalcoholic steatohepatitis-specific therapies, several drug candidates have demonstrated effect in the improvement in fibrosis or nonalcoholic steatohepatitis resolution. Further studies are needed to assess the effect of those interventions on cardiovascular outcomes, the major cause of mortality in patients with NAFLD. In conclusion, a more comprehensive, multidisciplinary approach to diagnosis and management of patients with NAFLD and cardiovascular diseases is needed to optimize clinical outcomes.
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Affiliation(s)
- Bing Chen
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, Pennsylvania
| | - W H Wilson Tang
- Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Mario Rodriguez
- John T. Milliken Department of Medicine, Division of Cardiovascular disease, Barnes-Jewish Hospital/Washington University in St. Louis School of Medicine, St. Louis, Missouri
| | - Kathleen E Corey
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Biykem Bozkurt
- Winters Center for Heart Failure Research, Cardiovascular Research Institute (B.B.), Baylor College of Medicine, DeBakey VA Medical Center, Houston, Texas
| | - Hafeez Ul Hassan Virk
- Harrington Heart & Vascular Institute, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Gregg S Pressman
- Division of Cardiovascular Diseases, Einstein Medical Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain.,Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas.,Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
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14
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Grigorescu ED, Lăcătușu CM, Floria M, Cazac GD, Onofriescu A, Ceasovschih A, Crețu I, Mihai BM, Șorodoc L. Association of Inflammatory and Metabolic Biomarkers with Mitral Annular Calcification in Type 2 Diabetes Patients. J Pers Med 2022; 12:1484. [PMID: 36143268 PMCID: PMC9502175 DOI: 10.3390/jpm12091484] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 08/28/2022] [Accepted: 09/07/2022] [Indexed: 07/30/2023] Open
Abstract
(1) Background: Type 2 diabetes mellitus (T2DM) contributes to cardiovascular disease and related mortality through the insidious effects of insulin resistance and chronic inflammation. Mitral annular calcification (MAC) is one such degenerative process promoted by T2DM. (2) Methods: This is a post hoc analysis of insulin resistance, inflammation, and hepatic steatosis markers in T2DM patients without atherosclerotic manifestations, but with incidental echocardiographic detection of mild MAC. (3) Results: 138 consenting patients were 49.3% men, 57.86 years old, with a history of T2DM of 6.16 years and HbA1c 8.06%, of whom sixty had mild MAC (43.47%). The statistically significant differences between patients with/without MAC were higher HOMA C-peptide and C-peptide index for insulin resistance, higher TNF-α for inflammation, and lower estimated glomerular filtration rate. High-sensitive C-reactive protein (hsCRP) was significantly associated with insulin resistance and the strength of the relationship was higher in the MAC group. Predictive of MAC were TNF-α, HOMA C-peptide, and especially hepatic steatosis and hypertension. (4) Conclusions: MAC was more prevalent than reported in the literature. Insulin resistance and inflammation were predictive of MAC, but significant markers differ across studies. Widely available routine tests and echocardiographic assessments are useful in the early identification of mitral annular calcifications in diabetes patients.
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Affiliation(s)
- Elena-Daniela Grigorescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Cristina-Mihaela Lăcătușu
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Mariana Floria
- Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Internal Medicine, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Georgiana-Diana Cazac
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Alina Onofriescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Alexandr Ceasovschih
- Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Internal Medicine, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Ioana Crețu
- Crețu R. Ioana PFA, 707020 Aroneanu, Romania
| | - Bogdan-Mircea Mihai
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Laurențiu Șorodoc
- Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Internal Medicine, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
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15
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Lazure P, Tomlinson JW, Kowdley KV, Magni P, Santos RD, Jacobs G, Murray S. Clinical practice gaps and challenges in non-alcoholic steatohepatitis care: An international physician needs assessment. Liver Int 2022; 42:1772-1782. [PMID: 35635757 PMCID: PMC9544805 DOI: 10.1111/liv.15324] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 05/25/2022] [Accepted: 05/27/2022] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND AIMS Even as several pharmacological treatments for non-alcoholic steatohepatitis (NASH) are in development, the incidence of NASH is increasing on an international scale. We aim to assess clinical practice gaps and challenges of hepatologists and endocrinologists when managing patients with NASH in four countries (Germany/Italy/United Kingdom/United States) to inform educational interventions. METHODS A sequential mixed-method design was used: qualitative semi-structured interviews followed by quantitative online surveys. Participants were hepatologists and endocrinologists practising in one of the targeted countries. Interview data underwent thematic analysis and survey data were analysed with chi-square and Kruskal-Wallis tests. RESULTS Most interviewees (n = 24) and surveyed participants (89% of n = 224) agreed that primary care must be involved in screening for NASH, yet many faced challenges involving and collaborating with them. Endocrinologists reported low knowledge of which blood markers to use when suspecting NASH (56%), when to order an MRI (65%) or ultrasound/FibroScan® (46%), and reported sub-optimal skills interpreting alanine aminotransferase (ALT, 37%) and aspartate aminotransferase (AST, 38%) blood marker test results, causing difficulty during diagnosis. Participants believed that more evidence is needed for upcoming therapeutic agents; yet, they reported sub-optimal knowledge of eligibility criteria for clinical trials. Knowledge and skill gaps when managing comorbidities, as well as skill gaps facilitating patient lifestyle changes were reported. CONCLUSIONS Educational interventions are needed to address the knowledge and skill gaps identified and to develop strategies to optimize patient care, which include implementing relevant care pathways, encouraging referrals and testing, and multidisciplinary collaboration, as suggested by the recent Global Consensus statement on NAFLD.
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Affiliation(s)
| | - Jeremy W. Tomlinson
- Oxford Centre for DiabetesEndocrinology and Metabolism (OCDEM) and NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill HospitalHeadingtonUK
| | - Kris V. Kowdley
- Liver Institute Northwest and Washington State UniversitySeattleWAUSA
| | - Paolo Magni
- Università degli Studi di MilanoMilanoItaly,IRCCS MultiMedicaMilanItaly,International Atherosclerosis SocietyMilanItaly
| | - Raul D. Santos
- International Atherosclerosis SocietyMilanItaly,Heart Institute (InCor) University of São Paulo Medical School HospitalSão PauloBrazil,Hospital Israelita Albert EinsteinSão PauloBrazil
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16
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Gedallovich SM, Ladner DP, VanWagner LB. Liver transplantation in the era of non-alcoholic fatty liver disease/metabolic (dysfunction) associated fatty liver disease: the dilemma of the steatotic liver graft on transplantation and recipient survival. Hepatobiliary Surg Nutr 2022; 11:425-429. [PMID: 35693416 PMCID: PMC9186195 DOI: 10.21037/hbsn-22-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 03/07/2022] [Indexed: 01/10/2025]
Affiliation(s)
- Seren M. Gedallovich
- Division of Palliative Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Daniela P. Ladner
- Division of Organ Transplantation, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Lisa B. VanWagner
- Division of Gastroenterology & Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- Division of Epidemiology, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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17
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Liu Y, Méric G, Havulinna AS, Teo SM, Åberg F, Ruuskanen M, Sanders J, Zhu Q, Tripathi A, Verspoor K, Cheng S, Jain M, Jousilahti P, Vázquez-Baeza Y, Loomba R, Lahti L, Niiranen T, Salomaa V, Knight R, Inouye M. Early prediction of incident liver disease using conventional risk factors and gut-microbiome-augmented gradient boosting. Cell Metab 2022; 34:719-730.e4. [PMID: 35354069 PMCID: PMC9097589 DOI: 10.1016/j.cmet.2022.03.002] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 01/06/2022] [Accepted: 03/08/2022] [Indexed: 02/08/2023]
Abstract
The gut microbiome has shown promise as a predictive biomarker for various diseases. However, the potential of gut microbiota for prospective risk prediction of liver disease has not been assessed. Here, we utilized shallow shotgun metagenomic sequencing of a large population-based cohort (N > 7,000) with ∼15 years of follow-up in combination with machine learning to investigate the predictive capacity of gut microbial predictors individually and in conjunction with conventional risk factors for incident liver disease. Separately, conventional and microbial factors showed comparable predictive capacity. However, microbiome augmentation of conventional risk factors using machine learning significantly improved the performance. Similarly, disease-free survival analysis showed significantly improved stratification using microbiome-augmented models. Investigation of predictive microbial signatures revealed previously unknown taxa for liver disease, as well as those previously associated with hepatic function and disease. This study supports the potential clinical validity of gut metagenomic sequencing to complement conventional risk factors for prediction of liver diseases.
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Affiliation(s)
- Yang Liu
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia.
| | - Guillaume Méric
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia; Baker Department of Cardiometabolic Health, The University of Melbourne, Melbourne, VIC, Australia; Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Aki S Havulinna
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; Institute of Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
| | - Shu Mei Teo
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Fredrik Åberg
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Matti Ruuskanen
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Internal Medicine, University of Turku, Turku, Finland
| | - Jon Sanders
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - Qiyun Zhu
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - Anupriya Tripathi
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA
| | - Karin Verspoor
- School of Computing and Information Systems, University of Melbourne, Melbourne, VIC, Australia; School of Computing Technologies, RMIT University, Melbourne, VIC, Australia
| | - Susan Cheng
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Mohit Jain
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA
| | - Pekka Jousilahti
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Yoshiki Vázquez-Baeza
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA; Department of Computer Science & Engineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, CA, USA
| | - Rohit Loomba
- NAFLD Research Center, Department of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - Leo Lahti
- Department of Computing, University of Turku, Turku, Finland
| | - Teemu Niiranen
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Internal Medicine, University of Turku, Turku, Finland; Division of Medicine, Turku University Hospital, Turku, Finland
| | - Veikko Salomaa
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Rob Knight
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA; Department of Computer Science & Engineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, CA, USA
| | - Michael Inouye
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia; Baker Department of Cardiometabolic Health, The University of Melbourne, Melbourne, VIC, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Health Data Research UK Cambridge, Wellcome Genome Campus, University of Cambridge, Cambridge, UK; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK; The Alan Turing Institute, London, UK.
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18
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Mahabaleshwarkar R, Liu TL, McKillop IH, Spencer M. The Association Between Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease Diagnosis Varies by Race. Metab Syndr Relat Disord 2022; 20:286-294. [PMID: 35319282 DOI: 10.1089/met.2021.0108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
Objectives: This study investigated how the association between metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) diagnosis varies between non-Hispanic African American and white patients. Methods: A retrospective cohort study was performed using electronic medical records from an integrated health care system (2010-2018). Adults with records for all MetS measurements (body mass index, lipids, blood pressure, and blood glucose) in 2011, who did not have a NAFLD diagnosis before their last MetS measurement, were included. Results: The study cohort consisted of 139,336 patients (age 56.1 ± 15.2 years, 57.9% female, 79.4% non-Hispanic white). The rate of NAFLD diagnosis was higher in MetS patients compared with non-MetS patients [adjusted hazards ratio (AHR) = 1.99, 95% CI = 1.91-2.09] with a significant interaction by race (AHR = 2.05, 95% CI = 1.95-2.15 in non-Hispanic whites vs. AHR = 1.76, 95% CI = 1.58-1.96 non-Hispanic African Americans, P = 0.017). Secondary analyses revealed that the relative NAFLD diagnosis rate was higher in non-Hispanic whites with MetS compared with non-Hispanic African Americans with MetS among females and patients 18-39 years of age and 40-59 years, but not among males and those ≥60 years of age. Conclusions: Non-Hispanic white patients with MetS, particularly females and those <60 years of age, may be at increased risk of NAFLD compared with non-Hispanic African American MetS patients and may benefit from extra attention regarding NAFLD screening.
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Affiliation(s)
- Rohan Mahabaleshwarkar
- Center for Outcomes Research and Evaluation, Atrium Health, Charlotte, North Carolina, USA
| | - Tsai-Ling Liu
- Center for Outcomes Research and Evaluation, Atrium Health, Charlotte, North Carolina, USA
| | - Iain H McKillop
- Department of Surgery, Atrium Health, Charlotte, North Carolina, USA
| | - Melanie Spencer
- Center for Outcomes Research and Evaluation, Atrium Health, Charlotte, North Carolina, USA
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19
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Kawada T. RE: Association of obstructive sleep apnea with non-alcoholic fatty liver disease in patients with obesity-an observational study. Eat Weight Disord 2022; 27:391-392. [PMID: 34165698 DOI: 10.1007/s40519-021-01246-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 06/10/2021] [Indexed: 10/21/2022] Open
Affiliation(s)
- Tomoyuki Kawada
- Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan.
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20
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Bettini S, Busetto L. Reply to letter: "RE: Association of obstructive sleep apnea with non-alcoholic fatty liver disease in patients with obesity: an observational study". Eat Weight Disord 2022; 27:393-394. [PMID: 34185307 DOI: 10.1007/s40519-021-01247-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 06/10/2021] [Indexed: 11/24/2022] Open
Affiliation(s)
- Silvia Bettini
- Department of Medicine, Internal Medicine 3, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.
| | - Luca Busetto
- Department of Medicine, Internal Medicine 3, University of Padova, Via Giustiniani 2, 35128, Padova, Italy
- Center for the Study and the Integrated Management of Obesity, Padova University Hospital, Padova, Italy
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21
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Bettini S, Serra R, Fabris R, Dal Prà C, Favaretto F, Dassie F, Duso C, Vettor R, Busetto L. Association of obstructive sleep apnea with non-alcoholic fatty liver disease in patients with obesity: an observational study. Eat Weight Disord 2022; 27:335-343. [PMID: 33811619 PMCID: PMC8019078 DOI: 10.1007/s40519-021-01182-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Obstructive Sleep Apnea (OSA) is associated with the presence and severity of Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to investigate the relationship between the severity of OSA and NAFLD and to recognize a polysomnographic parameter correlated with progression of fibrosis, determined by a non-invasive score of liver fibrosis, FIBrosis-4 index (FIB-4), in patients affected by severe obesity and OSA. METHODS We enrolled 334 patients (Body Mass Index, BMI 44.78 ± 8.99 kg/m2), divided into classes according to severity of OSA evaluated with Apnea Hypopnea Index (AHI): OSAS 0 or absent (17%), mild OSA (26%), moderate OSA (20%), severe OSAS (37%). We studied anthropometric, polysomnographic, biochemical data and FIB-4. A multiple regression model was computed to identify a polysomnographic independent predictor of FIB-4 among those parameters previously simple correlated with FIB-4. RESULTS The severity of OSA was associated with a decrease in High-Density Lipoprotein-cholesterol (HDL) and an increase in BMI, triglycerides, Homeostasis model assessment insulin-resistance index (HOMA), transaminases and FIB-4. FIB-4 correlated with sex, age, BMI, AHI, mean percentage oxyhaemoglobin (meanSaO2%), number of desaturations, platelets, transaminases, HDL, triglycerides and HOMA. The only variables independently related to FIB-4 were sex, BMI, triglycerides and meanSpO2 (r = 0.47, AdjRsqr = 0.197). CONCLUSION MeanSpO2% represented an independent determinant for the worsening of FIB-4 in patients with severe obesity and OSA. Hence, it could hypothesize a clinical role of meanSaO2% in recognizing patients with obesity and OSA and higher risk of developing advanced fibrosis and, thus, to undergo further investigation. LEVEL III Evidence obtained from well-designed cohort analytic studies.
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Affiliation(s)
- Silvia Bettini
- Department of Medicine, Internal Medicine 3, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.
| | - Roberto Serra
- Center for the Study and the Integrated Management of Obesity, Padova University Hospital, Padova, Italy
| | - Roberto Fabris
- Center for the Study and the Integrated Management of Obesity, Padova University Hospital, Padova, Italy
| | - Chiara Dal Prà
- Center for the Study and the Integrated Management of Obesity, Padova University Hospital, Padova, Italy
| | - Francesca Favaretto
- Department of Medicine, Internal Medicine 3, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.,Center for the Study and the Integrated Management of Obesity, Padova University Hospital, Padova, Italy
| | - Francesca Dassie
- Department of Medicine, Internal Medicine 3, University of Padova, Via Giustiniani 2, 35128, Padova, Italy
| | - Claudio Duso
- Department of Medicine, Internal Medicine 3, University of Padova, Via Giustiniani 2, 35128, Padova, Italy
| | - Roberto Vettor
- Department of Medicine, Internal Medicine 3, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.,Center for the Study and the Integrated Management of Obesity, Padova University Hospital, Padova, Italy
| | - Luca Busetto
- Department of Medicine, Internal Medicine 3, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.,Center for the Study and the Integrated Management of Obesity, Padova University Hospital, Padova, Italy
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22
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Gupta S, Walker S. Testing for cirrhosis. Aust Prescr 2022; 44:197-199. [PMID: 35002032 PMCID: PMC8671021 DOI: 10.18773/austprescr.2021.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Cirrhosis can be suspected by a thorough clinical assessment, but compensated liver disease is often asymptomatic. Select investigations are therefore critical for identifying patients with advanced liver disease and cirrhosis Biomarkers and validated serum tests can evaluate liver damage and synthetic function. The ratio of the concentration of aspartate aminotransferase to the platelet count can predict the presence of cirrhosis Non-invasive imaging techniques, from basic ultrasound to elastography, are critical adjuncts to the clinical assessment of cirrhosis. They reduce the need for liver biopsy Careful monitoring, prescribing and appropriate specialist referral are key considerations in cirrhosis management. Early diagnosis can help to improve the outcomes for patients.
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23
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Khan MS, Cuda S, Karere GM, Cox LA, Bishop AC. Breath biomarkers of insulin resistance in pre-diabetic Hispanic adolescents with obesity. Sci Rep 2022; 12:339. [PMID: 35013420 PMCID: PMC8748903 DOI: 10.1038/s41598-021-04072-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 12/15/2021] [Indexed: 12/14/2022] Open
Abstract
Insulin resistance (IR) affects a quarter of the world's adult population and is a major factor in the pathogenesis of cardio-metabolic disease. In this pilot study, we implemented a non-invasive breathomics approach, combined with random forest machine learning, to investigate metabolic markers from obese pre-diabetic Hispanic adolescents as indicators of abnormal metabolic regulation. Using the ReCIVA breathalyzer device for breath collection, we have identified a signature of 10 breath metabolites (breath-IR model), which correlates with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (R = 0.95, p < 0.001). A strong correlation was also observed between the breath-IR model and the blood glycemic profile (fasting insulin R = 0.91, p < 0.001 and fasting glucose R = 0.80, p < 0.001). Among tentatively identified metabolites, limonene, undecane, and 2,7-dimethyl-undecane, significantly cluster individuals based on HOMA-IR (p = 0.003, p = 0.002, and p < 0.001, respectively). Our breath-IR model differentiates between adolescents with and without IR with an AUC-ROC curve of 0.87, after cross-validation. Identification of a breath signature indicative of IR shows utility of exhaled breath metabolomics for assessing systemic metabolic dysregulation. A simple and non-invasive breath-based test has potential as a diagnostic tool for monitoring IR progression, allowing for earlier detection of IR and implementation of early interventions to prevent onset of type 2 diabetes mellitus.
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Affiliation(s)
- Mohammad S Khan
- Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
- Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
| | - Suzanne Cuda
- Health and Weight Management Clinic, Children's Hospital of San Antonio, San Antonio, TX, 78207, USA
- Baylor College of Medicine, Houston, TX, 77030, USA
| | - Genesio M Karere
- Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
- Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
| | - Laura A Cox
- Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
- Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
| | - Andrew C Bishop
- Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
- Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
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24
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Zhou Y, Liu Z, Qiao G, Tang B, Li P. Visualization of endoplasmic reticulum viscosity in the liver of mice with nonalcoholic fatty liver disease by a near-infrared fluorescence probe. CHINESE CHEM LETT 2021. [DOI: 10.1016/j.cclet.2021.04.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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25
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Zhou Y, Wu C, Wang X, Li P, Fan N, Zhang W, Liu Z, Zhang W, Tang B. Exploring the Changes of Peroxisomal Polarity in the Liver of Mice with Nonalcoholic Fatty Liver Disease. Anal Chem 2021; 93:9609-9620. [PMID: 34191493 DOI: 10.1021/acs.analchem.1c01776] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Peroxisome proliferator-activated receptor alpha (PPAR-a) is a crucial nuclear transcription regulator of lipid metabolism, which is closely associated with the initiation and development of nonalcoholic fatty liver disease (NAFLD). Because PPAR-a can directly decide the level of peroxisomal metabolic enzymes, its changes might directly cause variations in peroxisomal polarity. Therefore, we developed a new two-photon fluorescence imaging probe, PX-P, in which the triphenylamine and cyanide moieties can real-time sense peroxisomal polarity changes. Using PX-P, we observed a prominent decrease in the peroxisomal polarity in the liver of mice with NAFLD for the first time. More importantly, we discovered that intracellular excessive peroxynitrite (ONOO-) and hydrogen peroxide (H2O2) underwent nitrification and oxidation, respectively, with various sites of PPAR-a. Interestingly, the key site of PPAR-a was nitrated by a low concentration of ONOO- rather than being oxidized by the high level of H2O2. These drastically reduced the activity of PPAR-a, accelerating the occurrence of NAFLD. Moreover, through activating PPARs with pioglitazone, peroxisomal polarity markedly increased compared with that of NAFLD. Altogether, our work presents a new approach for the early diagnosis of NAFLD and identifies potential therapeutic targets.
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Affiliation(s)
- Yongqing Zhou
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Chuanchen Wu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Xin Wang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Ping Li
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Nannan Fan
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Wei Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Zhenzhen Liu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Wen Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China
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26
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Eletreby R, Abdellatif Z, Gaber Y, Ramadan A, Ahmad N, Khattab H, Said M, Saad Y. Validity of routine biochemical and ultrasound scores for prediction of hepatic fibrosis and steatosis in NAFLD. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00115-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
We evaluated the validity of some non-invasive scores and ultrasound findings to predict fibrosis and steatosis in a cohort of NAFLD patients who underwent liver biopsy. Ninety-seven NAFLD patients were enrolled and classified into NASH (66) and simple steatosis groups (31) based on liver biopsy. ROC curves were constructed for Fibrosis-4 index (FIB4), aspartate aminotransferase to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) in fibrosis prediction, also for (hepatic steatosis index; HSI, fatty liver index; FLI) and ultrasonographic subcutaneous and visceral adipose tissue measurements (SAT and VAT) for steatosis prediction.
Results
FIB4 had AUC of 0.6, APRI and NFS at cutoffs of 0.3 and -.2.4 had AUC of 0.64 and 0.63 in detecting the presence of any grade of fibrosis, and of (0.52, 0.55, and 0.58) for significant fibrosis. FIB4 at a cut-off of (0.76) had the highest AUC in detecting any grade of fibrosis in the simple steatosis group (0.81). SAT (at cutoff of 2.1 and 2.5) was superior to VAT. HSI (at cutoff 45.35 and 45.7) was superior to FLI in detecting moderate or marked steatosis.
Conclusion
FIB4 and NFS can be used in screening for silent liver disease with ongoing fibrosis in simple steatosis. They are unsatisfactory predictors for significant fibrosis in NAFLD. SAT is better than VAT in predicting moderate steatosis and is slightly better than biochemical HSI.
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27
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Ding L, De Munck TJI, Oligschlaeger Y, dos Reis IM, Verbeek J, Koek GH, Houben T, Shiri-Sverdlov R. Myosteatosis in NAFLD patients correlates with plasma Cathepsin D. Biomol Concepts 2021; 12:27-35. [DOI: 10.1515/bmc-2021-0004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 04/23/2021] [Indexed: 12/31/2022] Open
Abstract
Abstract
Previously, we have shown that hepatic lipid accumulation induces the secretion of cathepsin D (CTSD), and that plasma CTSD levels are associated with increased inflammation and disease severity in nonalcoholic fatty liver disease (NAFLD). Although it is clear that the liver is a major source of plasma CTSD, it is unknown whether other metabolically active organs such as the muscle, also associate with plasma CTSD levels in NAFLD patients. Therefore, the aim of this study was to explore the relation between lipid accumulation in the muscle (myosteatosis) and plasma CTSD levels in forty-five NAFLD patients. We observed that hepatic steatosis positively associated with plasma CTSD levels, confirming the previously established link between plasma CTSD and the liver. Furthermore, a positive association between myosteatosis and plasma CTSD levels was observed, which was independent of sex, age, BMI, waist circumference and hepatic steatosis. By establishing a positive association between myosteatosis and plasma CTSD levels, our findings suggest that, in addition to the liver, the muscle is also linked to plasma CTSD levels in NAFLD patients. The observed link between myosteatosis and plasma CTSD levels supports the concept of a significant role of the skeletal muscle in metabolic disturbances in metabolic syndrome-related disorders.
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Affiliation(s)
- Lingling Ding
- Department of Molecular Genetics, NUTRIM School of Nutrition and Translational Research in Metabolism , Maastricht University Medical Center+ , Universiteitssingel 50 , Maastricht , the Netherlands
| | - Toon. J. I. De Munck
- Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism , Maastricht University Medical Center+ , Universiteitssingel 50 , Maastricht , the Netherlands
| | - Yvonne Oligschlaeger
- Department of Molecular Genetics, NUTRIM School of Nutrition and Translational Research in Metabolism , Maastricht University Medical Center+ , Universiteitssingel 50 , Maastricht , the Netherlands
| | - Inês Magro dos Reis
- Department of Molecular Genetics, NUTRIM School of Nutrition and Translational Research in Metabolism , Maastricht University Medical Center+ , Universiteitssingel 50 , Maastricht , the Netherlands
| | - Jef Verbeek
- Department of Gastroenterology & Hepatology , University Hospitals KU Leuven , Herestraat 49 , Leuven Leuven , Belgium
| | - Ger. H. Koek
- Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism , Maastricht University Medical Center+ , Universiteitssingel 50 , Maastricht , the Netherlands
- Department of internal medicine, division of gastroenterology and hepatology , Maastricht University Medical Center . P. Debyelaan 25 , HX Maastricht , the Netherlands
| | - Tom Houben
- Department of Molecular Genetics, NUTRIM School of Nutrition and Translational Research in Metabolism , Maastricht University Medical Center+ , Universiteitssingel 50 , Maastricht , the Netherlands
| | - Ronit Shiri-Sverdlov
- Department of Molecular Genetics, NUTRIM School of Nutrition and Translational Research in Metabolism , Maastricht University Medical Center+ , Universiteitssingel 50 , Maastricht , the Netherlands
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28
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De Munck TJI, Boesch M, Verhaegh P, Masclee AAM, Jonkers D, van Pelt JF, du Plessis J, Korf H, Nevens F, Koek GH, Van der Merwe S, Verbeek J. Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease? PLoS One 2021; 16:e0251822. [PMID: 33989346 PMCID: PMC8121306 DOI: 10.1371/journal.pone.0251822] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 05/03/2021] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Neuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the role of Nrg4 in human NAFLD remains unclear to date. We analysed Nrg4 plasma levels and its association with liver disease severity together with the transcriptional profile of the Nrg4 pathway in liver and visceral adipose tissue (VAT) of NAFLD patients. METHODS Plasma Nrg4 levels were measured in 65 NAFLD patients and 43 healthy controls (HC). Hepatic steatosis and fibrosis were diagnosed and quantified with chemical shift MRI and transient elastography respectively. Furthermore, blood lipid levels, HOMA-IR and systemic pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ) were analysed. Microarray analyses to assess differences in the Nrg4 and its receptor family ErbB pathway in liver and VAT from an independent patient group with biopsy proven NAFL (simple steatosis) (n = 4), NASH (n = 5) and normal liver (n = 6) were performed. RESULTS Plasma Nrg4 levels were not significantly different between NAFLD patients and HC (p = 0.622). Furthermore, plasma Nrg4 levels did not correlate with the hepatic fat fraction (r = -0.028, p = 0.829) and were not significantly different between NAFLD patients with or without hepatic fibrosis (p = 0.087). Finally, the expression profile of 82 genes related to the Nrg4-ErbB pathway in liver and VAT was not significantly different between NAFL, NASH or obese controls. CONCLUSION Our study does not support a role for Nrg4 in the pathophysiology of human NAFLD.
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Affiliation(s)
- Toon J. I. De Munck
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Markus Boesch
- Laboratory of Hepatology, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, Leuven, Belgium
| | - Pauline Verhaegh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Ad A. M. Masclee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Daisy Jonkers
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Jos F. van Pelt
- Laboratory of Clinical Digestive Oncology, Department of Oncology, KU Leuven & University Hospitals Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium
| | - Johannie du Plessis
- Laboratory of Hepatology, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, Leuven, Belgium
| | - Hannelie Korf
- Laboratory of Hepatology, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, Leuven, Belgium
| | - Frederik Nevens
- Laboratory of Hepatology, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Ger H. Koek
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Schalk Van der Merwe
- Laboratory of Hepatology, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Jef Verbeek
- Laboratory of Hepatology, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- * E-mail:
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29
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Yun HH, Park S, Chung MJ, Son JY, Park JM, Jung SJ, Yim JH, Kang KK, Byeon S, Baek SM, Lee SW, Lee AR, Kim TH, Park JK, Jeong KS. Effects of losartan and l-serine in a mouse liver fibrosis model. Life Sci 2021; 278:119578. [PMID: 33965379 DOI: 10.1016/j.lfs.2021.119578] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 04/26/2021] [Accepted: 04/30/2021] [Indexed: 12/20/2022]
Abstract
Hepatic fibrosis is a common liver disease caused by excessive collagen deposition in the liver. Since liver transplantation is the only current treatment for cirrhosis with worsened fibrosis, a new strategy to develop anti-fibrosis drugs with no adverse effects is necessary. In recent studies, amino acids have been applied as a type of therapy in various fields. l-serine plays a major role in antioxidant production via the maintenance of nicotinamide adenine dinucleotide phosphate hydride production in the mitochondria. l-serine may reduce fibrotic lesions in a mouse model of chronic liver injury. This study used 27 six-week-old C57BL/6 mice and injected them three times a week for eight weeks with carbon tetrachloride (CCl4) (1.5 mg/kg, 10% v/v CCl4 in olive oil) to create a hepatic fibrosis mouse model. The mice, which weighed approximately 20-30 g, were randomly classified into four groups: 1) the olive oil group, which received intraperitoneal injection of olive oil (1.5 mg/kg, 3 times per week for 8 weeks); 2) the CCl4-only group; 3) the CCl4 + losartan (10 mg/kg, PO, 5 days on, weekend off for 8 weeks) group; and 4) the CCl4 + l-serine (100 g/L, free access for 8 weeks) group. Hematoxylin and eosin staining and Masson's trichrome staining showed reduced inflammatory cell deposition and collagen deposition in the liver tissue in the l-serine supplemented group. l-serine was found to reduce the spread of hepatic fibrosis and has potential use in clinical settings. Based on these histopathological observations, l-serine is a potential anti-fibrosis drug.
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Affiliation(s)
- Hyun Ho Yun
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Sunyoung Park
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Myung-Jin Chung
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Ji-Yoon Son
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Jae-Min Park
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Seung-Jun Jung
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Jae-Hyuk Yim
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Kyung-Ku Kang
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Seongrim Byeon
- Kainos Medicine Institute Inc., Seongnam, Republic of Korea
| | - Su-Min Baek
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Seoung-Woo Lee
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - A-Rang Lee
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Tae-Hwan Kim
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Jin-Kyu Park
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea
| | - Kyu-Shik Jeong
- Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, 41566 Daegu, Republic of Korea.
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Bettini S, Bombonato G, Dassie F, Favaretto F, Piffer L, Bizzotto P, Busetto L, Chemello L, Senzolo M, Merkel C, Angeli P, Vettor R, Milan G, Maffei P. Liver Fibrosis and Steatosis in Alström Syndrome: A Genetic Model for Metabolic Syndrome. Diagnostics (Basel) 2021; 11:diagnostics11050797. [PMID: 33924909 PMCID: PMC8170882 DOI: 10.3390/diagnostics11050797] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 04/18/2021] [Accepted: 04/24/2021] [Indexed: 12/27/2022] Open
Abstract
Alström syndrome (ALMS) is an ultra-rare monogenic disease characterized by insulin resistance, multi-organ fibrosis, obesity, type 2 diabetes mellitus (T2DM), and hypertriglyceridemia with high and early incidence of non-alcoholic fatty liver disease (NAFLD). We evaluated liver fibrosis quantifying liver stiffness (LS) by shear wave elastography (SWE) and steatosis using ultrasound sonographic (US) liver/kidney ratios (L/K) in 18 patients with ALMS and 25 controls, and analyzed the contribution of metabolic and genetic alterations in NAFLD progression. We also genetically characterized patients. LS and L/K values were significantly higher in patients compared with in controls (p < 0.001 versus p = 0.013). In patients, LS correlated with the Fibrosis-4 Index and age, while L/K was associated with triglyceride levels. LS showed an increasing trend in patients with metabolic comorbidities and displayed a significant correlation with waist circumference, the homeostasis model assessment, and glycated hemoglobin A1c. SWE and US represent promising tools to accurately evaluate early liver fibrosis and steatosis in adults and children with ALMS during follow-up. We described a new pathogenic variant of exon 8 in ALMS1. Patients with ALMS displayed enhanced steatosis, an early increased age-dependent LS that is associated with obesity and T2DM but also linked to genetic alterations, suggesting that ALMS1 could be involved in liver fibrogenesis.
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Affiliation(s)
- Silvia Bettini
- Internal Medicine 3, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (F.F.); (L.B.); (R.V.); (G.M.); (P.M.)
- Correspondence: (S.B.); (F.D.); Tel.: +39-333-204-6896 (S.B.); Tel.: +39-049-821-7021 (F.D.)
| | - Giancarlo Bombonato
- Internal Medicine 5, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (G.B.); (L.P.); (P.B.); (L.C.); (C.M.); (P.A.)
| | - Francesca Dassie
- Internal Medicine 3, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (F.F.); (L.B.); (R.V.); (G.M.); (P.M.)
- Correspondence: (S.B.); (F.D.); Tel.: +39-333-204-6896 (S.B.); Tel.: +39-049-821-7021 (F.D.)
| | - Francesca Favaretto
- Internal Medicine 3, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (F.F.); (L.B.); (R.V.); (G.M.); (P.M.)
| | - Luca Piffer
- Internal Medicine 5, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (G.B.); (L.P.); (P.B.); (L.C.); (C.M.); (P.A.)
| | - Paola Bizzotto
- Internal Medicine 5, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (G.B.); (L.P.); (P.B.); (L.C.); (C.M.); (P.A.)
| | - Luca Busetto
- Internal Medicine 3, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (F.F.); (L.B.); (R.V.); (G.M.); (P.M.)
| | - Liliana Chemello
- Internal Medicine 5, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (G.B.); (L.P.); (P.B.); (L.C.); (C.M.); (P.A.)
| | - Marco Senzolo
- Gastroenterology Department of Oncological and Gastroenterological Surgical Sciences, DiSCOG, University of Padua, 35128 Padua, Italy;
| | - Carlo Merkel
- Internal Medicine 5, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (G.B.); (L.P.); (P.B.); (L.C.); (C.M.); (P.A.)
| | - Paolo Angeli
- Internal Medicine 5, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (G.B.); (L.P.); (P.B.); (L.C.); (C.M.); (P.A.)
| | - Roberto Vettor
- Internal Medicine 3, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (F.F.); (L.B.); (R.V.); (G.M.); (P.M.)
| | - Gabriella Milan
- Internal Medicine 3, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (F.F.); (L.B.); (R.V.); (G.M.); (P.M.)
| | - Pietro Maffei
- Internal Medicine 3, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy; (F.F.); (L.B.); (R.V.); (G.M.); (P.M.)
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Moreto F, Ferron AJT, Francisqueti-Ferron FV, D'Amato A, Garcia JL, Costa MR, Silva CCVA, Altomare A, Correa CR, Aldini G, Ferreira ALA. Differentially expressed proteins obtained by label-free quantitative proteomic analysis reveal affected biological processes and functions in Western diet-induced steatohepatitis. J Biochem Mol Toxicol 2021; 35:1-11. [PMID: 33729641 DOI: 10.1002/jbt.22751] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 10/26/2020] [Accepted: 02/24/2021] [Indexed: 12/12/2022]
Abstract
Nonalcoholic steatohepatitis (NASH) is a pathological manifestation with a progressive incidence in response to the epidemic of hepatic steatosis caused primarily by excessive energy intake. The present study unravels affected biological processes and functions by the presence of NASH in rats using a label-free quantitative proteomic strategy. NASH was induced by a Western high-sugar and high-fat diet for 20 weeks. The liver tissue was collected for histology and for a mass spectrometry-based proteomic protocol. The NASH group showed severe lipidosis, hepatocyte ballooning, and the presence of collagen deposition. Among upregulated proteins in NASH perilipin-2 (Plin-2; F6QBA3; difference [diff]: 2.29), ferritin heavy (Fth1; Q66HI5; diff: 2.19) and light (Ftl1; P02793; diff: 1.75) chains, macrophage migration inhibitory factor 1 (Mif; P30904; diff: 1.69), and fibronectin (Fn1; F1LST1; diff: 0.35) were observed, whereas among downregulated proteins, plectin (Q6S399; diff: -3.34), some Cyp2 family proteins of the cytochrome P450 complex, glutathione S-transferases, flavin-containing monooxygenase 1 (Fmo1; P36365; diff: -2.08), acetyl-CoA acetyltransferase 2 (Acat2; Q5XI22; diff: -2.25), acyl-CoA oxidase 2 (Acox2; F1LNW3; diff: -1.59), and acyl-CoA oxidase 3 (Acox3; F1M9A7; diff: -2.41) were observed. Also, biological processes and functions such as LPS/IL-1 inhibition of RXR, fatty acid metabolism, Nrf2-mediated oxidative stress response, xenobiotic metabolism, and PXR/RXR and CAR/RXR activations were predicted to be affected. In conclusion, the liver of rats with NASH induced by Western diet shows a decreased capacity of metabolizing lipids, fatty acids, and xenobiotic compounds that predispose fibrosis development.
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Affiliation(s)
- Fernando Moreto
- Medical School, Sao Paulo State University, Botucatu, Brazil
| | | | | | - Alfonsina D'Amato
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | | | - Mariane R Costa
- Medical School, Sao Paulo State University, Botucatu, Brazil
| | | | | | | | - Giancarlo Aldini
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
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Association between serum interleukin (IL)-12 level and severity of non-alcoholic fatty liver disease (NAFLD). ACTA ACUST UNITED AC 2021; 59:66-72. [PMID: 33055315 DOI: 10.2478/rjim-2020-0029] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Indexed: 01/01/2023]
Abstract
What is new? Serum IL-12 level is associated with NAFLD severity. Elevation in serum IL-12 level is in line with more severe NAFLD based on BARD score and NAFLD fibrosis score. Positive correlation is observed between serum IL-12 level and BARD score.Introduction. Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Lipid accumulation in the liver triggers inflammation and leads to NAFLD. Prolonged inflammation will worsen the disease progression. Pro-inflammatory cytokines, including interleukin (IL)-12, plays a role in the inflammatory process. This study aimed to determine the association between IL-12 and NAFLD severity.Methods. A cross-sectional study was conducted between January and July 2019 in Haji Adam Malik Hospital Medan, Indonesia. Subjects were patients aged 18 years or older diagnosed with NAFLD based on ultrasound. Exclusion criteria were excessive alcohol consumption, other primary liver diseases, malignancies, and cardio-metabolic disturbances. Serum IL-12 level was determined using an enzyme-linked immunosorbent assay method. The severity of NAFLD was assessed using the BARD score and NAFLD fibrosis score.Results. A total of 100 subjects were enrolled with male predominant. The mean age of subjects was 54.97 ± 8.85 years, and the most frequent comorbidity was obesity. Most subjects had mild to moderate disease progression. Serum IL-12 level was higher in more severe NAFLD based on ultrasound grading (P < 0.001), BARD score (P = 0.003), and NAFLD fibrosis score (P = 0.005). A positive correlation was observed between serum IL-12 level and BARD score (P < 0.001) with sufficient accuracy (AUC = 0.691, P = 0.014).Conclusion. Serum IL-12 level was associated with the severity of NAFLD. Higher serum IL-12 level was observed in more severe NAFLD progression.
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Gerber Y, VanWagner LB, Yaffe K, Terry JG, Rana JS, Reis JP, Sidney S. Non-alcoholic fatty liver disease and cognitive function in middle-aged adults: the CARDIA study. BMC Gastroenterol 2021; 21:96. [PMID: 33653293 PMCID: PMC7927393 DOI: 10.1186/s12876-021-01681-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 02/19/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) risk factors that have been linked to cognitive decline. Whether NAFLD is associated with cognitive performance in midlife remains uncertain. METHODS Coronary Artery Risk Development in Young Adults study participants with CT examination and cognitive assessment at Y25 (2010-2011; n = 2809) were included. Cognitive function was reassessed at Y30. NAFLD was defined according to liver attenuation and treated both continuously and categorically (using ≤ 40 and ≤ 51 Hounsfield units to define severity) after exclusion for other causes of liver fat. Cognitive tests including the Digit Symbol Substitution (processing speed), Rey Auditory Verbal Learning (verbal memory), and Stroop (executive function) were analyzed with standardized z-scores. Linear models were constructed to (a) examine the cross-sectional associations of NAFLD with cognitive scores and (b) evaluate its predictive role in 5-year change in cognitive performance. RESULTS Participants' mean age (Y25) was 50.1 (SD 3.6) years (57% female; 48% black), with 392 (14%) having mild NAFLD and 281 (10%) having severe NAFLD. NAFLD was positively associated with CVD risk factors and inversely associated with cognitive scores. However, after adjustment for CVD risk factors, no associations were shown between NAFLD and cognitive scores (all βs ≈ 0). Similarly, no associations were observed with 5-year cognitive decline. CVD history, hypertension, smoking, diabetes and hypertriglyceridemia showed stronger associations with baseline cognitive scores and were predictive of subsequent cognitive decline (all P ≤ .05). CONCLUSION Among middle-aged adults, inverse associations between NAFLD and cognitive scores were attenuated after adjustment for CVD risk factors, with the latter predictive of poorer cognitive performance both at baseline and follow-up.
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Affiliation(s)
- Yariv Gerber
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, 6997801, Tel Aviv, Israel.
- Kaiser Permanente Northern California, Oakland, CA, USA.
- School of Public Health, University of California Berkeley, Berkeley, CA, USA.
| | - Lisa B VanWagner
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Kristine Yaffe
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - James G Terry
- Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jamal S Rana
- Kaiser Permanente Northern California, Oakland, CA, USA
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Jared P Reis
- National Heart Lung and Blood Institute, Bethesda, MD, USA
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Domech CR, Travieso JCF, Guridi ZD, Fernández MIC, del Vallín SL, Carralero AR, Batallie EF, Alvarez AMA, Dorta LF, Ferrer JI, Castaño SM, García MR, Rivero GJ, Alvarez YV. Comparative study of the effects of Abexol and atorvastatin in patients with non-alcoholic fatty liver disease. Clin Exp Hepatol 2021; 7:55-65. [PMID: 34027116 PMCID: PMC8122099 DOI: 10.5114/ceh.2021.104387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/04/2020] [Indexed: 11/17/2022] Open
Abstract
AIM OF THE STUDY To investigate the efficacy and safety of Abexol and atorvastatin in patients with non-alcoholic fatty liver disease (NAFLD).Material and methods: The present study had a monocentric, randomized, double-blinded, comparative design with 4 parallel groups - group 1 (Abexol), group 2 (atorvastatin), group 3 (combined therapy) and group 4 (placebo) - to which dietary recommendations and physical activity practice were provided twice a day, for 24 weeks. Significant changes in the ultrasound analysis of the liver were considered a primary efficacy variable. Insulin resistance improvement (HOMA2-IR) was considered as a co-primary efficacy criterion. Significant changes in the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lipid profile variables and the anthropometric variables were evaluated as secondary variables of effectiveness. Statistical analysis of all data was according to the intention to treat method. RESULTS The groups were statistically homogeneous at baseline conditions. At the end of the 6 months of treatment about 50% of the patients in all groups showed a decrease of at least one degree in echogenicity, while the rest remained the same. There were no significant changes in the values of liver enzymes or anthropometric variables evaluated. Treatment with atorvastatin and combined therapy significantly reduced levels of low-density lipoprotein-cholesterol (LDL-C) and total cholesterol. The treatments were safe and well tolerated, although in the atorvastatin group the number of adverse events reported was greater than in the rest of the groups. CONCLUSIONS Abexol and atorvastatin showed comparable efficacy and safety in patients with NAFLD, with advantages for treatment with atorvastatin with respect to its effects on the lipid profile of these patients.
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Mayer C, Richard L, Côme M, Ulmann L, Nazih H, Chénais B, Ouguerram K, Mimouni V. The Marine Microalga, Tisochrysis lutea, Protects against Metabolic Disorders Associated with Metabolic Syndrome and Obesity. Nutrients 2021; 13:430. [PMID: 33525643 PMCID: PMC7911999 DOI: 10.3390/nu13020430] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/20/2021] [Accepted: 01/27/2021] [Indexed: 12/14/2022] Open
Abstract
Long-chain polyunsaturated fatty acids n-3 series and especially docosahexaenoic acid are known to exert preventive effects on metabolic disturbances associated with obesity and decrease cardiovascular disease risk. n-3 LC-PUFAs are mainly consumed in the form of fish oil, while other sources, such as certain microalgae, may contain a high content of these fatty acids. The aim of this study was to evaluate the effects of Tisochrysis lutea (Tiso), a microalga rich in DHA, on metabolic disorders associated with obesity. Three male Wistar rat groups were submitted for eight weeks to a standard diet or high-fat and high fructose diet (HF), supplemented or not with 12% of T. lutea (HF-Tiso). The supplementation did not affect plasma alanine aminotransferase (ALAT). Bodyweight, glycemia and insulinemia decreased in HF-Tiso rats (ANOVA, p < 0.001), while total plasma cholesterol, high-density lipoprotein-cholesterol (HDL-C) increased (ANOVA, p < 0.001) without change of low-density lipoprotein-cholesterol (LDL-C) and triacylglycerol (TAG) levels. Tiso supplementation decreased fat mass and leptinemia as well as liver TAG, cholesterol and plasma tumor necrosis factor-alpha levels (ANOVA, p < 0.001) while it did not affect interleukin 6 (IL-6), IL-4 and lipopolysaccharides levels. HF-Tiso rats showed an increase of IL-10 level in abdominal adipose tissue (ANOVA, p < 0.001). In conclusion, these results indicated that DHA-rich T. lutea might be beneficial for the prevention of obesity and improvement of lipid and glucose metabolism.
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Affiliation(s)
- Claire Mayer
- EA 2160 MMS, Mer Molécules Santé, IUML FR 3473 CNRS, Institut Universitaire Technologique, Département Génie Biologique, Le Mans Université, CEDEX 9, 53020 Laval, France; (C.M.); (M.C.); (L.U.)
| | | | - Martine Côme
- EA 2160 MMS, Mer Molécules Santé, IUML FR 3473 CNRS, Institut Universitaire Technologique, Département Génie Biologique, Le Mans Université, CEDEX 9, 53020 Laval, France; (C.M.); (M.C.); (L.U.)
| | - Lionel Ulmann
- EA 2160 MMS, Mer Molécules Santé, IUML FR 3473 CNRS, Institut Universitaire Technologique, Département Génie Biologique, Le Mans Université, CEDEX 9, 53020 Laval, France; (C.M.); (M.C.); (L.U.)
| | - Hassan Nazih
- EA 2160 MMS, Mer Molécules Santé, IUML FR 3473 CNRS, UFR Pharmacie, Université de Nantes, CEDEX 1, 44035 Nantes, France;
| | - Benoît Chénais
- EA 2160 MMS, Mer Molécules Santé, IUML FR 3473 CNRS, UFR Sciences et Techniques, Le Mans Université, CEDEX 9, 72085 Le Mans, France;
| | - Khadija Ouguerram
- UMR1280 PhAN, Physiopathology of Nutritional Adaptations, INRAe, University of Nantes, CHU Hôtel Dieu, IMAD, CRNH Ouest, 44000 Nantes, France;
| | - Virginie Mimouni
- EA 2160 MMS, Mer Molécules Santé, IUML FR 3473 CNRS, Institut Universitaire Technologique, Département Génie Biologique, Le Mans Université, CEDEX 9, 53020 Laval, France; (C.M.); (M.C.); (L.U.)
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Finan B, Parlee SD, Yang B. Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH. Mol Metab 2020; 46:101153. [PMID: 33359400 PMCID: PMC8085542 DOI: 10.1016/j.molmet.2020.101153] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 12/17/2020] [Accepted: 12/19/2020] [Indexed: 12/13/2022] Open
Abstract
Background Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistance, and atherogenic dyslipidemia are pathological triggers for NASH progression. As these pathogenic features are common with obesity, type 2 diabetes (T2D), and atherosclerosis, therapies that target dysregulated core metabolic pathways may hold promise for treating NASH, particularly as first-line treatments. Scope of Review In this review, the latest clinical data on nuclear hormone- and peptide hormone-based drug candidates for NASH are reviewed and contextualized, culminating with a discovery research perspective on emerging combinatorial therapeutic approaches that merge nuclear and peptide strategies. Major Conclusion Several drug candidates targeting the metabolic complications of NASH have shown promise in early clinical trials, albeit with unique benefits and challenges, but questions remain regarding their translation to larger and longer clinical trials, as well as their utility in a more diseased patient population. Promising polypharmacological approaches can potentially overcome some of these perceived challenges, as has been suggested in preclinical models, but deeper characterizations are required to fully evaluate these opportunities.
Despite no approved treatments for NASH, several drug candidates have shown promise in early clinical trials. Therapies targeting metabolic pathologies of NASH have shown efficacy to reduce hepatic fat content and improve fibrosis. Many of these therapies have been rationally designed to mimic nuclear hormone or peptide hormone action. Despite provocative preclinical findings of nuclear and peptide hormone combination, clinical translation remains unproven.
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Affiliation(s)
- Brian Finan
- Novo Nordisk Research Center Indianapolis, Inc., United States.
| | | | - Bin Yang
- Novo Nordisk Research Center Indianapolis, Inc., United States
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Miptah HN, Ramli AS, Mohamad M, Hashim H, Tharek Z. Non-alcoholic fatty liver disease (NAFLD) and the cardiovascular disease (CVD) risk categories in primary care: is there an association? BMC FAMILY PRACTICE 2020; 21:238. [PMID: 33218301 PMCID: PMC7679975 DOI: 10.1186/s12875-020-01306-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 11/09/2020] [Indexed: 02/06/2023]
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is an emerging novel cardiovascular disease (CVD) risk factor. It’s prevalence is increasing globally. However, there is paucity in the evidence showing the association between NAFLD and CVD risk in primary care setting. Therefore, the objectives of this study were to determine the prevalence and factors associated with NAFLD among patients with ≥1 risk factor for NAFLD or CVD attending primary care clinics. Methodology A cross sectional study was conducted in two clinics at a university primary care centre. Patients aged ≥18 years with ≥1 risk factor for NAFLD or CVD were recruited. Participants with history of established liver disease or chronic alcohol use were excluded. Socio-demographics, clinical related data, anthropometric measurements and blood investigation results were recorded in a proforma. Diagnosis of NAFLD was made using abdominal ultrasound. The 10-year CVD risk was calculated using the general Framingham Risk Score (FRS). Multiple logistic regression (MLogR) was performed to identify independent factors associated with NAFLD. Results A total of 263 participants were recruited. The mean age was 52.3 ± 14.7 years old. Male and female were equally distributed. Majority of the participants were Malays (79.8%). The overall prevalence of NAFLD was 54.4% (95%CI 48,60%). Participants in the high FRS category have higher prevalence of NAFLD (65.5%), followed by those in the moderate category (55.4%) and the low category (46.3%), p = 0.025. From MLogR, independent factors associated with NAFLD were being employed (OR = 2.44, 95%CI 1.26,4.70, p = 0.008), obesity with BMI ≥27.5 (OR = 2.89, 95%CI 1.21,6.91, p = 0.017), elevated fasting glucose ≥5.6 mmol/L (OR = 2.79, 95%CI 1.44,5.43, p = 0.002), ALT ≥34 U/L (OR = 3.70, 95%CI 1.85,7.44, p < 0.001) and high FRS category (OR = 2.82, 95%CI 1.28,6.23, p = 0.010). Conclusion NAFLD is highly prevalent among patients with ≥1 risk factor for NAFLD or CVD in these primary care clinics. Patients who were obese, have elevated fasting glucose, elevated ALT and in the high FRS category were more likely to have NAFLD. This study underscores the importance of targeted screening for NAFLD in those with risk factors in primary care. Aggressive intervention must be executed in those with NAFLD in order to reduce CVD complications and risk of progression.
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Affiliation(s)
- Hayatul Najaa Miptah
- Department of Primary Care Medicine, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Selayang Campus, Jalan Prima Selayang 7, 68100, Batu Caves, Selangor, Malaysia
| | - Anis Safura Ramli
- Department of Primary Care Medicine, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Selayang Campus, Jalan Prima Selayang 7, 68100, Batu Caves, Selangor, Malaysia. .,Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM), Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000, Sungai Buloh, Selangor, Malaysia.
| | - Mariam Mohamad
- Department of Population Health and Preventive Medicine, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia
| | - Hilwati Hashim
- Department of Radiology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000, Sungai Buloh, Selangor, Malaysia
| | - Zahirah Tharek
- Department of Primary Care Medicine, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Selayang Campus, Jalan Prima Selayang 7, 68100, Batu Caves, Selangor, Malaysia
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Zhou Y, Li P, Wang X, Wu C, Fan N, Liu X, Wu L, Zhang W, Zhang W, Liu Z, Tang B. In situ visualization of peroxisomal viscosity in the liver of mice with non-alcoholic fatty liver disease by near-infrared fluorescence and photoacoustic imaging. Chem Sci 2020; 11:12149-12156. [PMID: 34094429 PMCID: PMC8163019 DOI: 10.1039/d0sc02922j] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 10/02/2020] [Indexed: 12/15/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) can gradually develop into hepatic failure, and early diagnosis is crucial to improve treatment efficiency. The occurrence of NAFLD is closely related to lipid metabolism. Peroxisomes act as the first and main site for lipid metabolism in the hepatocytes, so abnormal lipid metabolism might directly affect peroxisomal viscosity. Herein, we developed a new near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging probe (PV-1) for the real-time visualization of peroxisomal viscosity in vivo. This PV-1 encompasses the malononitrile group as the rotor, which emits strong NIRF (at 705 nm) and PA (at 680 nm) signals when rotation is hindered as viscosity increases. Through dual-mode imaging, we discovered distinctly higher viscosity in the liver of NAFLD mice for the first time. We further found the remarkable amelioration of NAFLD upon treatment with N-acetylcysteine (NAC). Therefore, we anticipate that the PV-1 imaging method is promising for the early diagnosis and prognostic evaluation of NAFLD.
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Affiliation(s)
- Yongqing Zhou
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Ping Li
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Xin Wang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Chuanchen Wu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Nannan Fan
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Xiaoning Liu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Lijie Wu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Wei Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Wen Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Zhenzhen Liu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
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Aja P, Ekpono E, Awoke J, Famurewa A, Izekwe F, Okoro E, Okorie C, Orji C, Nwite F, Ale B, Aku A, Igwenyi I, Nwali B, Orji O, Ani O, Ozoemena C, Anizoba G. Hesperidin ameliorates hepatic dysfunction and dyslipidemia in male Wistar rats exposed to cadmium chloride. Toxicol Rep 2020; 7:1331-1338. [PMID: 33088721 PMCID: PMC7559536 DOI: 10.1016/j.toxrep.2020.09.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 09/08/2020] [Accepted: 09/29/2020] [Indexed: 12/20/2022] Open
Abstract
The ever-increasing human population with attendant industrialization poses serious global health challenge. Cadmium (Cd) with other heavy metals contribute greatly to environmental pollutions and humans are daily exposed to them, leading to diverse ailments. We explored whether Hesperidin (HSP) could protect against hepatic damage and dyslipidemia in Wistar rats exposed to Cd. Forty wistar rats were randomly assigned into five groups (n = 8). Group 1 received 2 mL/kg body weight of normal saline; Group 2 received 100 mg/kg body weight of HSP while Group 3 received 5 mg/kg body weight of Cadmium Chloride (CdCl2) for 28 days. Group 4 received 100 mg/kg body weight of HSP and after 90 min, CdCl2 (5 mg/kg) body weight was administered for 28 days. Group 5 received 50 mg/kg body weight of HSP and after 90 min, CdCl2 (5 mg/kg) body weight was administered for 28 days. The serum lipid profiles, hepatic dysfunction and oxidative stress markers were determined using standard methods. Cd toxicity in rats prominently elevated serum activities of AST, ALT, ALP and levels of total bilirubin, direct bilirubin, cholesterol, LDL-C and malondialdehyde with decreased levels of HDL-C, triglycerides, superoxide dismutase, catalase, glutathione and body weights. The pre-treatment of HSP before Cd intoxication prevented the dysregulated activities of liver enzymes and levels of lipid profiles, enzymatic and non-enzymatic antioxidants and other biomarkers investigated, thus suggesting anti-hyperlipidemic and hepato-protective potentials. HSP may have great potentials for development of therapeutics that could enhance the management of dyslipidemia and liver disorders associated with heavy metal exposure.
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Affiliation(s)
- P.M. Aja
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - E.U. Ekpono
- Department of Science Laboratory Technology, Biochemistry Option, Federal Polytechnic Oko, Anambra State, Nigeria
| | - J.N. Awoke
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - A.C. Famurewa
- Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, Alex-Ekwueme Federal University, Ndufu-Alike, Ikwo, Ebonyi State, Nigeria
| | - F.I. Izekwe
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - E.J. Okoro
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - C.F. Okorie
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - C.L. Orji
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - F. Nwite
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - B.A. Ale
- Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Nigeria
| | - A.F. Aku
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - I.O. Igwenyi
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - B.U. Nwali
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - O.U. Orji
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - O.G. Ani
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - C.R. Ozoemena
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
| | - G.C. Anizoba
- Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria
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40
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Tariq T, Desai AP. Nonalcoholic Fatty Liver Disease: Making the Diagnosis. Clin Liver Dis (Hoboken) 2020; 16:53-57. [PMID: 32922750 PMCID: PMC7474145 DOI: 10.1002/cld.924] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 01/08/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Tooba Tariq
- Division of GeriatricsIndiana University School of MedicineIndianapolisIN
| | - Archita P. Desai
- Division of Gastroenterology and HepatologyIndiana University School of MedicineIndianapolisIN
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Younossi ZM, Corey KE, Alkhouri N, Noureddin M, Jacobson I, Lam B, Clement S, Basu R, Gordon SC, Ravendhra N, Puri P, Rinella M, Scudera P, Singal AK, Henry L. Clinical assessment for high-risk patients with non-alcoholic fatty liver disease in primary care and diabetology practices. Aliment Pharmacol Ther 2020; 52:513-526. [PMID: 32598051 DOI: 10.1111/apt.15830] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 04/21/2020] [Accepted: 05/12/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Primary care practitioners (PCPs) and diabetologists are at the frontline of potentially encountering patients with NASH. Identification of those at high risk for adverse outcomes is important. AIM To provide practical guidance to providers on how to identify these patients and link them to specialty care. METHODS US members of the Global Council on NASH evaluated the evidence about NASH and non-invasive tests and developed a simple algorithm to identify high-risk NASH patients for diabetologists and primary care providers. These tools can assist frontline providers in decision-making and referral to gastroenterology/hepatology practices for additional assessments. RESULTS The presence of NASH-related advanced fibrosis is an independent predictor of adverse outcomes. These patients with NASH are considered high risk and referral to specialists is warranted. Given that staging of fibrosis requires a liver biopsy, non-invasive tests for fibrosis would be preferred. Consensus recommendation from the group is to risk-stratify patients based on metabolic risk factors using the FIB-4 as the initial non-invasive test due to its simplicity and ease of use. A FIB-4 score ≥1.3 can be used for further assessment and linkage to specialty care where additional technology to assess liver stiffness or serum fibrosis test will be available. CONCLUSION Due to the growing burden of NAFLD and NASH, PCPs and diabetologists are faced with increased patient encounters in their clinical practices necessitating referral decisions. To assist in identifying high-risk NASH patients requiring specialty care, we provide a simple and easy to use algorithm.
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Petta S, Ting J, Saragoni S, Degli Esposti L, Shreay S, Petroni ML, Marchesini G. Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy. Nutr Metab Cardiovasc Dis 2020; 30:1014-1022. [PMID: 32423665 DOI: 10.1016/j.numecd.2020.02.016] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 02/21/2020] [Accepted: 02/24/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Nonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among hospitalized patients with AdvLD due to NASH in Italy. METHODS AND RESULTS Adult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017. Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs. CONCLUSION NAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.
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Affiliation(s)
- Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy.
| | - Jie Ting
- Gilead Sciences, Inc., Health Economics & Outcomes Research, Foster City, CA, USA
| | | | | | - Sanatan Shreay
- Gilead Sciences, Inc., Health Economics & Outcomes Research, Foster City, CA, USA
| | - Maria Letizia Petroni
- Department of Medical and Surgical Sciences, "Alma Mater" University, Bologna, Italy
| | - Giulio Marchesini
- Department of Medical and Surgical Sciences, "Alma Mater" University, Bologna, Italy
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Fernandez-Travieso JC, Rodriguez-Perez I, Ruenes-Domech C, lIlnait-Ferrer J, Fernandez-Dorta L, Mendoza-Castano S. Benefits of the Therapy With Abexol in Patients With Non-Alcoholic Fatty Liver Disease. Gastroenterology Res 2020; 13:73-80. [PMID: 32362966 PMCID: PMC7188363 DOI: 10.14740/gr1273] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 03/05/2020] [Indexed: 12/12/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diseases ranging from steatosis to steatohepatitis and cirrhosis. Given the increasing incidence of NAFLD and the long-term consequences of this disease, it is important to identify the risk factors and therapeutic measures. Abexol is a mixture of beeswax alcohols with antioxidant, gastro-protective and anti-inflammatory effects. The aim was to conduct a pooled analysis of clinical trials data of the effects of Abexol treatment in patients with NAFLD. Methods The present analysis includes the data of all patients with NAFLD obtained from medium-term randomized, double-blinded, placebo controlled clinical studies with Abexol. One hundred patients with NAFLD received Abexol (100 mg/day) or placebo for 6 months. Significant changes in the ultrasound analysis of the liver were considered a primary efficacy variable. Secondary endpoints were decreased homeostasis model assessment (HOMA) index and insulin levels, and improved clinical symptoms. Statistical analysis of all data was according to the intention-to-treat method. Results Both groups were statistically homogeneous at baseline conditions. At 6 months of treatment, the number of Abexol-treated patients exhibiting a normal liver echo pattern on ultrasonography was greater than that of the placebo patients (P < 0.05). Abexol significantly reduced (P < 0.05) insulin levels and HOMA index. The proportion of Abexol patients showing symptom improvement was higher (P < 0.01) than that of the placebo group. Treatments were safe and well tolerated. Conclusions Treatment of Abexol during 6 months significantly ameliorates liver fat accumulation and insulin resistances, meanwhile improving clinical evolution in patients with NAFLD. The treatment was safe and well tolerated in these patients.
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Cruz JF, Ferrari YAC, Machado CP, Santana NN, Mota AVH, Lima SO. SARCOPENIA AND SEVERITY OF NON-ALCOHOLIC FATTY LIVER DISEASE. ARQUIVOS DE GASTROENTEROLOGIA 2020; 56:357-360. [PMID: 31618396 DOI: 10.1590/s0004-2803.201900000-66] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 08/14/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease is characterized by deposition of lipids in the hepatic parenchyma exceeding 5% of liver weight in the absence of other conditions, such as viral or alcoholic hepatitis and metabolic disease. Non-alcoholic fatty liver disease is the most common form of chronic liver disease in several countries. In addition to liver complications, recent studies have shown a relation between liver fat and sarcopenia. OBJECTIVE Determine the association between sarcopenia and the severity of non-alcoholic hepatic steatosis diagnosed by abdominal ultrasonography. METHODS A clinical, cross-sectional study was conducted with a sample of male and female adults (18 to 70 years of age) submitted to ultrasonography for the investigation of non-alcoholic hepatic steatosis. Evaluations were also performed for the determination of upper and lower limb muscle strength. Data analysis was performed with the aid of the SPSS 22.0 program and involved ANCOVA and the Bonferroni post hoc test, with P-value <0.05 considered indicative of statistical significance. RESULTS One hundred two patients were submitted to abdominal ultrasonography, 57.8% of whom presented some degree of non-alcoholic hepatic steatosis. The presence and degree of fatty liver infiltration were significantly associated with the sarcopenic index, determined by the ratio between upper and lower limb strength and BMI (P=0.009 and post-test P=0.028 for upper limbs; P=0.006 and post-test P=0.013 for lower limbs). CONCLUSION In the present study, an association was found between the sarcopenic index and non-alcoholic hepatic steatosis, with an inversely proportional relation between this index and the severity of fatty infiltration. This finding offers further evidence of the metabolic interaction of the liver, adipose tissue and muscle.
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Cleveland ER, Ning H, Vos MB, Lewis CE, Rinella ME, Carr JJ, Lloyd-Jones DM, VanWagner LB. Low Awareness of Nonalcoholic Fatty Liver Disease in a Population-Based Cohort Sample: the CARDIA Study. J Gen Intern Med 2019; 34:2772-2778. [PMID: 31595464 PMCID: PMC6854130 DOI: 10.1007/s11606-019-05340-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 07/11/2019] [Accepted: 08/21/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, yet little is known about NAFLD awareness in individuals with incidental fatty liver on imaging. OBJECTIVE To assess the level of awareness of imaging-defined NAFLD among individuals with and without metabolic risk factors. DESIGN Cross-sectional analysis within a prospective longitudinal population-based cohort study conducted in four U.S. cities. PARTICIPANTS Adults age 43 to 55 years enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study who underwent computed tomography and a personal health questionnaire at the year 25 exam (2010-2011, n = 2788). MAIN MEASURES NAFLD was defined as liver attenuation ≤ 51 Hounsfield units after exclusion of other causes of liver fat. Participants were considered "NAFLD aware" if they reported being told previously by a doctor or nurse that they had "fatty liver." KEY RESULTS NAFLD prevalence was 23.9%. Only 16 of 667 (2.4%) participants with CT-defined NAFLD were aware of a NAFLD diagnosis. NAFLD aware participants were more likely to be white (81.3% vs. 53.5%, p = 0.03) and have the metabolic syndrome (87.5% vs. 59.3%, p = 0.02) and/or hypertension (75.0% vs. 50.2%, p = 0.05). In multivariable analyses adjusted for demographics, metabolic syndrome and hypertension remained predictive of NAFLD awareness. CONCLUSION There is low awareness of NAFLD among individuals with hepatic steatosis on imaging, even among those with metabolic risk factors. These findings highlight an opportunity to raise public and practitioner awareness of NAFLD with the goal of increasing diagnosis and implementing early treatment strategies.
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Affiliation(s)
- Erin R Cleveland
- Department of Medicine-Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St., Suite 1400, Chicago, IL, 60611, USA
| | - Hongyan Ning
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Miriam B Vos
- Department of Pediatrics-Division of Gastroenterology, Hepatology & Nutrition, Emory University, Atlanta, GA, 30322, USA
| | - Cora E Lewis
- Department of Medicine-Division of Preventive Medicine, University of Alabama Birmingham, Birmingham, AL, 35294, USA
| | - Mary E Rinella
- Department of Medicine-Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St., Suite 1400, Chicago, IL, 60611, USA
| | - John Jeffrey Carr
- Department of Radiology, Vanderbilt University, Nashville, TN, 37235, USA
| | - Donald M Lloyd-Jones
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
- Department of Medicine-Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Lisa B VanWagner
- Department of Medicine-Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St., Suite 1400, Chicago, IL, 60611, USA.
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
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Kelly N, Wattacheril J. Nonalcoholic Fatty Liver Disease: Evidence-Based Management and Early Recognition of Nonalcoholic Steatohepatitis. J Nurse Pract 2019. [DOI: 10.1016/j.nurpra.2019.06.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Lee SJ, Kim SU. Noninvasive monitoring of hepatic steatosis: controlled attenuation parameter and magnetic resonance imaging-proton density fat fraction in patients with nonalcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol 2019; 13:523-530. [PMID: 31018719 DOI: 10.1080/17474124.2019.1608820] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
With an increase in the worldwide prevalence of obesity, the incidence of non-alcoholic fatty liver disease (NAFLD) has been on the rise, such that it has been recently considered to be a major public health concern. Traditional interventions, such as lifestyle modifications, regular exercise, and healthy diet, have been significant in improving NAFLD with reduction of liver fat. Areas covered: Although liver biopsy is still the gold standard for diagnosis of NAFLD, there is a need for non-invasive, quantitative assessments of hepatic steatosis, especially in clinical trials of anti-steatotic medications or in the follow-up of patients undergoing lifestyle modifications. Liver biopsy has various shortcomings, such as invasive nature, risk of complications and possibility of sampling error. Therefore, it is impractical to use liver biopsy routinely in patients with NAFLD, clearly indicating the need for non-invasive and accurate diagnostic methods. Recently, controlled attenuation parameter (CAP) and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) have been employed in various studies to monitor the dynamic changes of hepatic steatosis in response to treatment in patients with NAFLD. Expert commentary: Although further validations are required, CAP and MRI-PDFF could be used as potential diagnostic and monitoring tools in clinical setting.
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Affiliation(s)
- Sol Jae Lee
- a Department of Internal Medicine , Yonsei University College of Medicine , Seoul , South Korea.,b Yonsei Liver Center , Severance Hospital , Seoul , South Korea
| | - Seung Up Kim
- a Department of Internal Medicine , Yonsei University College of Medicine , Seoul , South Korea.,b Yonsei Liver Center , Severance Hospital , Seoul , South Korea.,c Institute of Gastroenterology , Yonsei University College of Medicine , Seoul , South Korea
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Bettini S, Bordigato E, Milan G, Dal Pra' C, Favaretto F, Belligoli A, Sanna M, Serra R, Foletto M, Prevedello L, Busetto L, Fassina G, Vettor R, Fabris R. SCCA-IgM as a Potential Biomarker of Non-Alcoholic Fatty Liver Disease in Patients with Obesity, Prediabetes and Diabetes Undergoing Sleeve Gastrectomy. Obes Facts 2019; 12:291-306. [PMID: 31104052 PMCID: PMC6696770 DOI: 10.1159/000499717] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 03/16/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. OBJECTIVE The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. METHOD Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. RESULTS At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. CONCLUSIONS Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD.
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MESH Headings
- Adult
- Antigens, Neoplasm/blood
- Antigens, Neoplasm/immunology
- Biomarkers/blood
- Diabetes Mellitus, Type 2/blood
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/diagnosis
- Diabetes Mellitus, Type 2/surgery
- Female
- Follow-Up Studies
- Gastrectomy/methods
- Gastrectomy/rehabilitation
- Humans
- Immunoglobulin M/blood
- Male
- Middle Aged
- Non-alcoholic Fatty Liver Disease/blood
- Non-alcoholic Fatty Liver Disease/complications
- Non-alcoholic Fatty Liver Disease/diagnosis
- Non-alcoholic Fatty Liver Disease/surgery
- Obesity/blood
- Obesity/complications
- Obesity/diagnosis
- Obesity/surgery
- Obesity, Morbid/blood
- Obesity, Morbid/complications
- Obesity, Morbid/diagnosis
- Obesity, Morbid/surgery
- Prediabetic State/blood
- Prediabetic State/complications
- Prediabetic State/diagnosis
- Prediabetic State/surgery
- Prognosis
- Risk Factors
- Serpins/blood
- Serpins/immunology
- Treatment Outcome
- Weight Loss
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Affiliation(s)
- Silvia Bettini
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy,
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy,
| | - Emanuel Bordigato
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Gabriella Milan
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Chiara Dal Pra'
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Francesca Favaretto
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Anna Belligoli
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Marta Sanna
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Roberto Serra
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Mirto Foletto
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Luca Prevedello
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Luca Busetto
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | | | - Roberto Vettor
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Roberto Fabris
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
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