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Bourganou MV, Chondrogianni ME, Kyrou I, Flessa CM, Chatzigeorgiou A, Oikonomou E, Lambadiari V, Randeva HS, Kassi E. Unraveling Metabolic Dysfunction-Associated Steatotic Liver Disease Through the Use of Omics Technologies. Int J Mol Sci 2025; 26:1589. [PMID: 40004054 PMCID: PMC11855544 DOI: 10.3390/ijms26041589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 02/07/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is the most prevalent liver disorder globally, linked to obesity, type 2 diabetes, and cardiovascular risk. Understanding its potential progression from simple steatosis to cirrhosis and hepatocellular carcinoma (HCC) is crucial for patient management and treatment strategies. The disease's complexity requires innovative approaches for early detection and personalized care. Omics technologies-such as genomics, transcriptomics, proteomics, metabolomics, and exposomics-are revolutionizing the study of MASLD. These high-throughput techniques allow for a deeper exploration of the molecular mechanisms driving disease progression. Genomics can identify genetic predispositions, whilst transcriptomics and proteomics reveal changes in gene expression and protein profiles during disease evolution. Metabolomics offers insights into the metabolic alterations associated with MASLD, while exposomics links environmental exposures to MASLD progression and pathology. By integrating data from various omics platforms, researchers can map out the intricate biochemical pathways involved in liver disease progression. This review discusses the roles of omics technologies in enhancing the understanding of disease progression and highlights potential diagnostic and therapeutic targets within the MASLD spectrum, emphasizing the need for non-invasive tools in disease staging and treatment development.
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Affiliation(s)
- Maria V. Bourganou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.V.B.); (M.E.C.); (C.-M.F.)
| | - Maria Eleni Chondrogianni
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.V.B.); (M.E.C.); (C.-M.F.)
- Endocrine Unit, 1st Department of Propaedeutic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Ioannis Kyrou
- Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, 11855 Athens, Greece
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Centre for Health & Life Sciences, Coventry University, Coventry CV1 5FB, UK
- Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK
- College of Health, Psychology and Social Care, University of Derby, Derby DE22 IGB, UK
| | - Christina-Maria Flessa
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.V.B.); (M.E.C.); (C.-M.F.)
| | - Antonios Chatzigeorgiou
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527 Athens, Greece;
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, “Sotiria” Thoracic Diseases Hospital of Athens, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Vaia Lambadiari
- 2nd Department of Internal-Medicine, Diabetes Centre, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Harpal S. Randeva
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Centre for Health & Life Sciences, Coventry University, Coventry CV1 5FB, UK
| | - Eva Kassi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.V.B.); (M.E.C.); (C.-M.F.)
- Endocrine Unit, 1st Department of Propaedeutic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
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Xia F, Wei W, Wang J, Wang Y, Wang K, Zhang C, Zhu Q. Ultrasound radiomics-based logistic regression model for fibrotic NASH. BMC Gastroenterol 2025; 25:66. [PMID: 39920586 PMCID: PMC11806536 DOI: 10.1186/s12876-025-03605-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 01/10/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND Those who have severe fibrosis (F2 ≥ 2 stage) are at the greatest risk for the advancement of the illness among non-alcoholic fatty liver patients. To forecast the non-alcoholic steatohepatitis (NASH) probability accompanied by significant fibrosis, we propose to develop and validate a nomogram liver imaging reporting and data system, providing robust evidence for preventing and treating clinical liver diseases. METHODS The study used SD rats to create a model of hepatic steatosis and fibrosis by feeding them a high-fat diet and injecting Ccl4 subcutaneously. Radiomics characteristics were derived from two-dimensional liver ultrasound images of the rats, and a radiomics model was constructed, with rad-scores calculated accordingly. Univariate and multivariate logistic regression was employed to ascertain the clinical characteristics of rats and liver elasticity values, aiming to establish a clinical model. Ultimately, a clinical radiomics model was created by integrating the rad-score from the radiomics model with independent clinical characteristics from the clinical model. A forest plot was generated to depict this integration. The forest plot's performance was assessed by the use of the area under the receiver operating characteristic (ROC) curve (AUC), decision curve analysis, and calibration curve. RESULTS The areas under the receiver operating characteristic curve (AUC) for the training set and validation set of the clinical radiomics model were 0.986 and 0.971, respectively. Decision curve analysis showed that the clinical radiomics model had the highest net benefit across most threshold probability ranges. CONCLUSION The nomogram and clinical radiomics model, which consists of clinical characteristics, real-time shear wave elastography, and radiomics, provide excellent predictive capability in assessing the likelihood of fibrotic NASH.
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Affiliation(s)
- Fei Xia
- Department of Ultrasound, WuHu Hospital, East China Normal University, (The Second People's Hospital, WuHu), No.259 Jiuhuashan Road, Jinghu District, Wuhu, 241001, Anhui, China
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Shushan District, No.218 Jixi Road, Hefei, 230022, Anhui, China
| | - Wei Wei
- Department of Ultrasound, The First Affiliated Hospital of Wannan Medical College(Yijishan Hospital), NO.2 Zheshan West Road, Wuhu, 241000, China
| | - Junli Wang
- Department of Ultrasound, WuHu Hospital, East China Normal University, (The Second People's Hospital, WuHu), No.259 Jiuhuashan Road, Jinghu District, Wuhu, 241001, Anhui, China
| | - Yuhe Wang
- Department of Ultrasound, WuHu Hospital, East China Normal University, (The Second People's Hospital, WuHu), No.259 Jiuhuashan Road, Jinghu District, Wuhu, 241001, Anhui, China
| | - Kun Wang
- Department of Ultrasound, WuHu Hospital, East China Normal University, (The Second People's Hospital, WuHu), No.259 Jiuhuashan Road, Jinghu District, Wuhu, 241001, Anhui, China
| | - Chaoxue Zhang
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Shushan District, No.218 Jixi Road, Hefei, 230022, Anhui, China.
| | - Qiwei Zhu
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Shushan District, No.218 Jixi Road, Hefei, 230022, Anhui, China
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Cheng Y, Chen L, Zhu H, Ge Y, Li L, Guo Y, Wang X, You S, He G, Xue S. Baseline liver fibrosis-4 score correlates to the progression of anxiety and cognitive impairment in patients with Parkinson's disease. Front Aging Neurosci 2025; 17:1501319. [PMID: 39925858 PMCID: PMC11802528 DOI: 10.3389/fnagi.2025.1501319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 01/10/2025] [Indexed: 02/11/2025] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) or liver fibrosis may share similar pathophysiological features with Parkinson's disease (PD), yet their correlation was unclear. This study aimed to explore their correlation between PD and liver fibrosis using the fibrosis-4 score (FIB-4) as a surrogate marker. Methods We analyzed Parkinson's Progression Markers Initiative (PPMI) data and enrolled PD patients with comprehensive baseline and 5-year follow-up time-point clinical data. Participants were categorized based on FIB-4 levels to assess the association between FIB-4 scores and various clinical scales, controlling for potential confounders. Differences in the progression of clinical scales over five years were compared using generalized linear mixed models (GLMM). Results Baseline FIB-4 levels positively correlated to scores of baseline section III of the Unified-Parkinson Disease Rating Scale (UPDRS III) (r = 0.145, p = 0.017), Epworth Sleepiness Scale (EPSS) (r = 0.140, P = 0.022), Hopkins Verbal Learning Test (HVLT)-delayed recall (r = 0.128, P = 0.036) and HVLT-retention (r = 0.128, p = 0.036). GLMM analysis revealed an independent correlation between FIB-4 subgroup*time and several clinical scales including the State-trait Anxiety Inventory (STAI), Symbol Digit Modalities Test (SDMT), Semantic Fluency Test (SF), HVLT-total recall, and HVLT-delayed recall, with the high FIB-4 subgroup exhibiting a greater decline in these scores compared to the low FIB-4 subgroup (all p<0.05). Conclusion Elevated baseline FIB-4 correlated to more severe baseline daytime sleepiness, motor symptoms, and memory function in PD patients, along with a more rapid decline in cognitive functions such as executive function, information processing ability, and memory. Additionally, a high FIB-4 might confer a protective effect against anxiety.
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Affiliation(s)
- Yongqing Cheng
- Department of Neurology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, China
- Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Li Chen
- Department of Ophthalmology, Funing County People’s Hospital, Yancheng, Jiangsu, China
| | - Honghong Zhu
- Department of Rheumatology and Immunology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, China
| | - Yingchao Ge
- Department of Neurology, Qidong Hospital Affiliated to Nantong University, Nantong, Jiangsu, China
| | - Lei Li
- Department of Neurology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, China
| | - Yan Guo
- Department of Neurology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, China
| | - Xin Wang
- Department of Radiology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, China
| | - Shuangfei You
- Department of Neurology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, China
| | - Guojun He
- Department of Neurology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, China
| | - Shouru Xue
- Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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Yan R, Cao Y. The Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation for the Management of Obesity and Non-Alcoholic Fatty Liver Disease: Recent Updates. Biomedicines 2025; 13:206. [PMID: 39857788 PMCID: PMC11762999 DOI: 10.3390/biomedicines13010206] [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: 12/09/2024] [Revised: 01/05/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
Epigallocatechin gallate (EGCG) is the predominant bioactive catechin in green tea, and it has been ascribed a range of beneficial health effects. Current increases in obesity and non-alcoholic fatty liver disease (NAFLD) rates represent a persistent and burdensome threat to global public health. While many clinical studies have demonstrated that EGCG is associated with positive effects on various health parameters, including metabolic biomarkers, waist circumference, and body weight when consumed by individuals affected by obesity and NAFLD, there are also some reports suggesting that it may entail some degree of hepatotoxicity. The present review provides a comprehensive summary of the extant clinical findings pertaining to the safety and effectiveness of EGCG in managing obesity and NAFLD, with a particular focus on how treatment duration and dose level affect the bioactivity of this compound.
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Affiliation(s)
| | - Yanli Cao
- Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, China;
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Li Y, Wang L, Yi Q, Luo L, Xiong Y. Regulation of bile acids and their receptor FXR in metabolic diseases. Front Nutr 2024; 11:1447878. [PMID: 39726876 PMCID: PMC11669848 DOI: 10.3389/fnut.2024.1447878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 11/13/2024] [Indexed: 12/28/2024] Open
Abstract
High sugar, high-fat diets and unhealthy lifestyles have led to an epidemic of obesity and obesity-related metabolic diseases, seriously placing a huge burden on socio-economic development. A deeper understanding and elucidation of the specific molecular biological mechanisms underlying the onset and development of obesity has become a key to the treatment of metabolic diseases. Recent studies have shown that the changes of bile acid composition are closely linked to the development of metabolic diseases. Bile acids can not only emulsify lipids in the intestine and promote lipid absorption, but also act as signaling molecules that play an indispensable role in regulating bile acid homeostasis, energy expenditure, glucose and lipid metabolism, immunity. Disorders of bile acid metabolism are therefore important risk factors for metabolic diseases. The farnesol X receptor, a member of the nuclear receptor family, is abundantly expressed in liver and intestinal tissues. Bile acids act as endogenous ligands for the farnesol X receptor, and erroneous FXR signaling triggered by bile acid dysregulation contributes to metabolic diseases, including obesity, non-alcoholic fatty liver disease and diabetes. Activation of FXR signaling can reduce lipogenesis and inhibit gluconeogenesis to alleviate metabolic diseases. It has been found that intestinal FXR can regulate hepatic FXR in an organ-wide manner. The crosstalk between intestinal FXR and hepatic FXR provides a new idea for the treatment of metabolic diseases. This review focuses on the relationship between bile acids and metabolic diseases and the current research progress to provide a theoretical basis for further research and clinical applications.
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Affiliation(s)
| | | | | | | | - Yuxia Xiong
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
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Wang M, Wang X, Wang Y, Gai Y, Ye J, Xu X, You X. Advances in the study of the mechanism of action of miR‑22 in liver lesions (Review). Oncol Lett 2024; 28:541. [PMID: 39310022 PMCID: PMC11413475 DOI: 10.3892/ol.2024.14674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/15/2024] [Indexed: 09/25/2024] Open
Abstract
Globally, nearly 2 million deaths annually are attributed to the development of liver diseases, with liver cancer and cirrhosis being particularly prominent, which makes liver disease a significant global health concern. Cirrhosis is closely linked to the evolution of hepatitis, hepatic fibrosis and fatty liver. However, most liver diseases have an insidious onset, are challenging to treat and the prognosis and efficacy of current therapies are unsatisfactory, which can result in irreversible functional damage to the liver. Therefore, there is an urgent need to explore the molecular mechanisms underlying liver disease and identify new biomarkers and therapeutic targets. In previous years, microRNAs (miRs), a class of short non-coding RNAs comprising 17-25 nucleotides, have attracted attention for their roles in various types of liver diseases. Among them, miR-22 serves a unique role in mediating multiple pathway mechanisms and epigenetic modifications and can act both as an inhibitor of liver cancer and a metabolic blocker. Given its close association with the liver, several studies have reported that the differential expression of miR-22 regulates the metabolic process of liver cancer and is involved in the evolution of hepatic fibrosis and steatohepatitis, making it a potential target for early diagnosis and treatment. The present manuscript aimed to comprehensively review the key role of miR-22 in the evolution of liver diseases and offer valuable references and guidance for subsequent studies by identifying its specific mechanism of action and future development prospects.
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Affiliation(s)
- Minghe Wang
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Xuejing Wang
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Yanqi Wang
- College of Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Yikuo Gai
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Jingran Ye
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Xinyan Xu
- College of Second Clinical Medical, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Xue You
- Lin He's Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, Jining, Shandong 272067, P.R. China
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Emara MH, Soliman H, Said EM, Elbatae H, Elazab M, Elhefnawy S, Zaher TI, Abdel-Razik A, Elnadry M. Intermittent fasting and the liver: Focus on the Ramadan model. World J Hepatol 2024; 16:1070-1083. [PMID: 39221099 PMCID: PMC11362902 DOI: 10.4254/wjh.v16.i8.1070] [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: 02/22/2024] [Revised: 05/24/2024] [Accepted: 07/09/2024] [Indexed: 08/21/2024] Open
Abstract
Intermittent fasting (IF) is an intervention that involves not only dietary modifications but also behavioral changes with the main core being a period of fasting alternating with a period of controlled feeding. The duration of fasting differs from one regimen to another. Ramadan fasting (RF) is a religious fasting for Muslims, it lasts for only one month every one lunar year. In this model of fasting, observers abstain from food and water for a period that extends from dawn to sunset. The period of daily fasting is variable (12-18 hours) as Ramadan rotates in all seasons of the year. Consequently, longer duration of daily fasting is observed during the summer. In fact, RF is a peculiar type of IF. It is a dry IF as no water is allowed during the fasting hours, also there are no calorie restrictions during feeding hours, and the mealtime is exclusively nighttime. These three variables of the RF model are believed to have a variable impact on different liver diseases. RF was evaluated by different observational and interventional studies among patients with non-alcoholic fatty liver disease and it was associated with improvements in anthropometric measures, metabolic profile, and liver biochemistry regardless of the calorie restriction among lean and obese patients. The situation is rather different for patients with liver cirrhosis. RF was associated with adverse events among patients with liver cirrhosis irrespective of the underlying etiology of cirrhosis. Cirrhotic patients developed new ascites, ascites were increased, had higher serum bilirubin levels after Ramadan, and frequently developed hepatic encephalopathy and acute upper gastrointestinal bleeding. These complications were higher among patients with Child class B and C cirrhosis, and some fatalities occurred due to fasting. Liver transplant recipients as a special group of patients, are vulnerable to dehydration, fluctuation in blood immunosuppressive levels, likelihood of deterioration and hence observing RF without special precautions could represent a real danger for them. Patients with Gilbert syndrome can safely observe RF despite the minor elevations in serum bilirubin reported during the early days of fasting.
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Affiliation(s)
- Mohamed H Emara
- Department of Hepatology, Gastroenterology and Infectious Diseases, Kafrelsheikh University, Kafr-Elshikh 33516, Egypt
- Department of Medicine, Alyousif Hospital, Alkhobar 34622, Saudi Arabia.
| | - Hanan Soliman
- Department of Tropical Medicine and Infectious Diseases, Tanta University, Tanta 31512, Egypt
| | - Ebada M Said
- Department of Hepatology, Gastroenterology and Infectious Diseases, Benha University, Benha 13511, Egypt
| | - Hassan Elbatae
- Department of Hepatology, Gastroenterology and Infectious Diseases, Kafrelsheikh University, Kafr-Elshikh 33516, Egypt
| | - Mostafa Elazab
- Department of Hepatology, Gastroenterology and Infectious Diseases, Kafrelsheikh University, Kafr-Elshikh 33516, Egypt
| | - Shady Elhefnawy
- Department of Hepatology, Gastroenterology and Infectious Diseases, Kafrelsheikh University, Kafr-Elshikh 33516, Egypt
| | - Tarik I Zaher
- Department of Tropical Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Ahmed Abdel-Razik
- Department of Tropical Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Mohamed Elnadry
- Department of Hepato-Gastroenterology and Infectious Diseases, Al-Azhar University, Cairo 11651, Egypt
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Lara-Romero C, Romero-Gómez M. Treatment Options and Continuity of Care in Metabolic-associated Fatty Liver Disease: A Multidisciplinary Approach. Eur Cardiol 2024; 19:e06. [PMID: 38983581 PMCID: PMC11231815 DOI: 10.15420/ecr.2023.34] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 02/14/2024] [Indexed: 07/11/2024] Open
Abstract
The terms non-alcoholic fatty liver disease and non-alcoholic steatohepatitis have some limitations as they use exclusionary confounder terms and the use of potentially stigmatising language. Recently, a study with content experts and patients has been set to change this nomenclature. The term chosen to replace non-alcoholic fatty liver disease was metabolic dysfunction-associated steatotic liver disease (MASLD), which avoids stigmatising and helps improve awareness and patient identification. MASLD is the most common cause of chronic liver disease with an increasing prevalence, accounting for 25% of the global population. It is considered the hepatic manifestation of the metabolic syndrome with lifestyle playing a fundamental role in its physiopathology. Diet change and physical activity are the cornerstones of treatment, encompassing weight loss and healthier behaviours and a holistic approach. In Europe, there is no approved drug for MASLD to date and there is a substantial unmet medical need for effective treatments for patients with MASLD. This review not only provides an update on advances in evidence for nutrition and physical activity interventions but also explores the different therapeutic options that are being investigated and whose development focuses on the restitution of metabolic derangements and halting inflammatory and fibrogenic pathways.
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Affiliation(s)
- Carmen Lara-Romero
- Gastroenterology and Hepatology Department, Virgen del Rocío University Hospital Seville, Spain
- Clinical and Translational Research in Digestive Diseases, Institute of Biomedicine of Seville, University of Seville Seville, Spain
| | - Manuel Romero-Gómez
- Gastroenterology and Hepatology Department, Virgen del Rocío University Hospital Seville, Spain
- Clinical and Translational Research in Digestive Diseases, Institute of Biomedicine of Seville, University of Seville Seville, Spain
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Masson W, Barbagelata L, Godinez-Leiva E, Genua I, Nogueira JP. Association between hepatic steatosis and lipoprotein(a) levels in non-alcoholic patients: A systematic review. Indian J Gastroenterol 2024; 43:536-547. [PMID: 38036914 DOI: 10.1007/s12664-023-01457-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 09/02/2023] [Indexed: 12/02/2023]
Abstract
BACKGROUND AND OBJECTIVES It is well known that lipid abnormalities exist in the context of non-alcoholic fatty liver disease (NAFLD). The association between lipoprotein(a) [Lp(a)] levels and NAFLD is poorly understood. The main objective of the present study was to assess the association between Lp(a) levels and NAFLD. METHODS This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42023392526). A literature search was performed to detect studies that evaluated the association between Lp(a) levels, NAFLD and steatohepatitis (NASH). RESULTS Ten observational studies, including 40,045 patients, were identified and considered eligible for this systematic review. There were 9266 subjects in the NAFLD groups and 30,779 individuals in the respective control groups. Five studies evaluated patients with NAFLD (hepatic steatosis was associated with lower Lp(a) levels in four studies, while the remaining showed opposite results). Two studies evaluating NASH patients showed that Lp(a) levels were not different compared to controls. However, the increment of Lp(a) levels was correlated with liver fibrosis in one of them. In addition, one study analyzed simultaneously patients with NAFLD and NASH, showing a neutral result in NAFLD patients and a positive relationship in NASH patients. Two studies that included patients with the new definition of metabolic-associated fatty liver disease (MAFLD) also showed neutral results. CONCLUSION Although there could be an association between Lp(a) levels and hepatic steatosis, the results of the studies published to date are contradictory and not definitive.
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Affiliation(s)
- Walter Masson
- Servicio de Cardiología, Hospital Italiano de Buenos Aires, Perón 4190, C1199ABB, Ciudad Autónoma de Buenos Aires, Argentina
| | - Leandro Barbagelata
- Servicio de Cardiología, Hospital Italiano de Buenos Aires, Perón 4190, C1199ABB, Ciudad Autónoma de Buenos Aires, Argentina.
| | - Eddison Godinez-Leiva
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
- Universidad Internacional de Las Américas, San José, Costa Rica
| | - Idoia Genua
- Endocrinology and Nutrition Department, Hospital de La Santa Creu I Sant Pau, Autonomous University of Barcelona (UAB), Barcelona, Spain
- Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
| | - Juan Patricio Nogueira
- Centro de Investigación en Endocrinología, Nutrición Y Metabolismo (CIENM), Facultad de Ciencias de La Salud, Universidad Nacional de Formosa, Formosa, Argentina
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Zhang Y, Wang Y, Liao X, Liu T, Yang F, Yang K, Zhou Z, Fu Y, Fu T, Sysa A, Chen X, Shen Y, Lyu J, Zhao Q. Glutamine prevents high-fat diet-induced hepatic lipid accumulation in mice by modulating lipolysis and oxidative stress. Nutr Metab (Lond) 2024; 21:12. [PMID: 38459503 PMCID: PMC10924388 DOI: 10.1186/s12986-024-00784-1] [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: 09/27/2023] [Accepted: 02/06/2024] [Indexed: 03/10/2024] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is related to metabolic dysfunction and is characterized by excess fat storage in the liver. Several studies have indicated that glutamine could be closely associated with lipid metabolism disturbances because of its important role in intermediary metabolism. However, the effect of glutamine supplementation on MAFLD progression remains unclear. Here, we used a high-fat diet (HFD)-induced MAFLD C57BL/6 mouse model, and glutamine was supplied in the drinking water at different time points for MAFLD prevention and reversal studies. A MAFLD prevention study was performed by feeding mice an HFD concomitant with 4% glutamine treatment for 24 weeks, whereas the MAFLD reversal study was performed based on 4% glutamine treatment for 13 weeks after feeding mice an HFD for 10 weeks. In the prevention study, glutamine treatment ameliorated serum lipid storage, hepatic lipid injury, and oxidative stress in HFD-induced obese mice, although glutamine supplementation did not affect body weight, glucose homeostasis, energy expenditure, and mitochondrial function. In the MAFLD reversal study, there were no noticeable changes in the basic physiological phenotype and hepatic lipid metabolism. In summary, glutamine might prevent, but not reverse, HFD-induced MAFLD in mice, suggesting that a cautious attitude is required regarding its use for MAFLD treatment.
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Affiliation(s)
- Yongjie Zhang
- School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Yangli Wang
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
- School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Xin Liao
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Tong Liu
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Fengyuan Yang
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Kaiqiang Yang
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Zhuohua Zhou
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Yinxu Fu
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Ting Fu
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Aliaksei Sysa
- Belarusian State University, ISEI BSU, Minsk, Republic of Belarus
| | - Xiandan Chen
- Belarusian State University, ISEI BSU, Minsk, Republic of Belarus
| | - Yao Shen
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
| | - Jianxin Lyu
- School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China.
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China.
- Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
| | - Qiongya Zhao
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China.
- Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
- School of Public Health, Hangzhou Medical College, Hangzhou, China.
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11
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Petermann‐Rocha F, Carrasco‐Marin F, Boonpor J, Parra‐Soto S, Shannon O, Malcomson F, Phillips N, Jain M, Deo S, Livingstone KM, Dingle SE, Mathers JC, Forrest E, Ho FK, Pell JP, Celis‐Morales C. Association of five diet scores with severe NAFLD incidence: A prospective study from UK Biobank. Diabetes Obes Metab 2024; 26:860-870. [PMID: 37997550 PMCID: PMC11497349 DOI: 10.1111/dom.15378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/26/2023] [Accepted: 11/05/2023] [Indexed: 11/25/2023]
Abstract
AIM This study aimed to contrast the associations of five common diet scores with severe non-alcoholic fatty liver disease (NAFLD) incidence. MATERIALS AND METHODS In total, 162 999 UK Biobank participants were included in this prospective population-based study. Five international diet scores were included: the 14-Item Mediterranean Diet Adherence Screener (MEDAS-14), the Recommended Food Score (RFS), the Healthy Diet Indicator (HDI), the Mediterranean Diet Score and the Mediterranean-DASH Intervention for Neurodegenerative Delay score. As each score has different measurements and scales, all scores were standardized and categorized into quartiles. Cox proportional hazard models adjusted for confounder factors investigated associations between the standardized quartiles and severe NAFLD incidence. RESULTS Over a median follow-up of 10.2 years, 1370 participants were diagnosed with severe NAFLD. When the analyses were fully adjusted, participants in quartile 4 using the MEDAS-14 and RFS scores, as well as those in quartiles 2 and 3 using the HDI score, had a significantly lower risk of severe incident NAFLD compared with those in quartile 1. The lowest risk was observed in quartile 4 for the MEDAS-14 score [hazard ratio (HR): 0.76 (95% confidence interval (CI): 0.62-0.94)] and the RFS score [HR: 0.82 (95% CI: 0.69-0.96)] and as well as in quartile 2 in the HDI score [HR: 0.80 (95% CI: 0.70-0.91)]. CONCLUSION MEDAS-14, RFS and HDI scores were the strongest diet score predictors of severe NAFLD. A healthy diet might protect against NAFLD development irrespective of the specific approach used to assess diet. However, following these score recommendations could represent optimal dietary approaches to mitigate NAFLD risk.
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Affiliation(s)
- Fanny Petermann‐Rocha
- School of Cardiovascular and Metabolic HealthUniversity of GlasgowGlasgowUK
- Centro de Investigación Biomédica, Facultad de MedicinaUniversidad Diego PortalesSantiagoChile
| | - Fernanda Carrasco‐Marin
- School of Cardiovascular and Metabolic HealthUniversity of GlasgowGlasgowUK
- Centro de Vida SaludableUniversidad de ConcepciónConcepciónChile
| | - Jirapitcha Boonpor
- School of Cardiovascular and Metabolic HealthUniversity of GlasgowGlasgowUK
- Faculty of Public HealthKasetsart University, Chalermphrakiat Sakon Nakhon Province Campus, Kasetsart UniversitySakon NakhonThailand
| | - Solange Parra‐Soto
- School of Cardiovascular and Metabolic HealthUniversity of GlasgowGlasgowUK
- Department of Nutrition and Public HealthUniversidad del Bío‐BíoChillánChile
| | - Oliver Shannon
- Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences InstituteNewcastle UniversityNewcastle upon TyneUK
| | - Fiona Malcomson
- Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences InstituteNewcastle UniversityNewcastle upon TyneUK
| | - Nathan Phillips
- School of Cardiovascular and Metabolic HealthUniversity of GlasgowGlasgowUK
| | - Mahek Jain
- School of Cardiovascular and Metabolic HealthUniversity of GlasgowGlasgowUK
| | - Salil Deo
- School of Health and WellbeingUniversity of GlasgowGlasgowUK
- Surgical Services, Louis Stokes Cleveland VA Medical CenterClevelandOhioUSA
- Case School of MedicineCase Western Reserve UniversityClevelandOhioUSA
| | - Katherine M. Livingstone
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition SciencesDeakin UniversityGeelongVictoriaAustralia
| | - Sara E. Dingle
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition SciencesDeakin UniversityGeelongVictoriaAustralia
| | - John C. Mathers
- Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences InstituteNewcastle UniversityNewcastle upon TyneUK
| | - Ewan Forrest
- Department of Gastroenterology, Glasgow Royal InfirmaryUniversity of GlasgowGlasgowUK
| | - Frederick K. Ho
- School of Health and WellbeingUniversity of GlasgowGlasgowUK
| | - Jill P. Pell
- School of Health and WellbeingUniversity of GlasgowGlasgowUK
| | - Carlos Celis‐Morales
- School of Cardiovascular and Metabolic HealthUniversity of GlasgowGlasgowUK
- Human Performance Laboratory, Education, Physical Activity and Health Research UnitUniversidad Católica del MauleTalcaChile
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12
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Zhong H, Dong J, Zhu L, Mao J, Dong J, Zhao Y, Zou Y, Guo M, Ding G. Non-alcoholic fatty liver disease: pathogenesis and models. Am J Transl Res 2024; 16:387-399. [PMID: 38463579 PMCID: PMC10918142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 01/22/2024] [Indexed: 03/12/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a complex disease characterized by a massive accumulation of lipids in the liver, with a continuous progression of simple steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Non-alcoholic fatty liver disease is associated with obesity, insulin resistance, and metabolic syndrome; it is a severe public health risk and is currently the most common liver disease of the world. In addition to the fatty infiltration of the liver in non-alcoholic fatty liver disease patients, the field of liver transplantation faces similar obstacles. NAFLD and NASH primarily involve lipotoxicity, inflammation, oxidative stress, and insulin resistance. However, the precise mechanisms and treatments remain unclear. Therapeutic approaches encompass exercise, weight control, as well as treatments targeting antioxidants and anti-inflammatory pathways. The role of animal models in research has become crucial as a key tool to explore the molecular mechanisms and potential treatments for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Here, we summarized the current understanding of the pathogenesis of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis and discussed animal models commonly used in recent years.
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Affiliation(s)
- Hanxiang Zhong
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical UniversityShanghai, China
| | - Jiayong Dong
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical UniversityShanghai, China
| | - Liye Zhu
- National Key Laboratory of Immunity and Inflammation & Institute of Immunology, Navy Medical UniversityShanghai, China
| | - Jiaxi Mao
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical UniversityShanghai, China
| | - Junfeng Dong
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical UniversityShanghai, China
| | - Yuanyu Zhao
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical UniversityShanghai, China
| | - You Zou
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical UniversityShanghai, China
| | - Meng Guo
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical UniversityShanghai, China
- National Key Laboratory of Immunity and Inflammation & Institute of Immunology, Navy Medical UniversityShanghai, China
| | - Guoshan Ding
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical UniversityShanghai, China
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13
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Ali H, Shahzil M, Moond V, Shahzad M, Thandavaram A, Sehar A, Waseem H, Siddiqui T, Dahiya DS, Patel P, Tillmann H. Non-Pharmacological Approach to Diet and Exercise in Metabolic-Associated Fatty Liver Disease: Bridging the Gap between Research and Clinical Practice. J Pers Med 2024; 14:61. [PMID: 38248762 PMCID: PMC10817352 DOI: 10.3390/jpm14010061] [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: 12/01/2023] [Revised: 12/23/2023] [Accepted: 12/29/2023] [Indexed: 01/23/2024] Open
Abstract
This review provides a practical and comprehensive overview of non-pharmacological interventions for metabolic-associated fatty liver disease (MASLD), focusing on dietary and exercise strategies. It highlights the effectiveness of coffee consumption, intermittent fasting, and Mediterranean and ketogenic diets in improving metabolic and liver health. The review emphasizes the importance of combining aerobic and resistance training as a critical approach to reducing liver fat and increasing insulin sensitivity. Additionally, it discusses the synergy between diet and exercise in enhancing liver parameters and the role of gut microbiota in MASLD. The paper underscores the need for a holistic, individualized approach, integrating diet, exercise, gut health, and patient motivation. It also highlights the long-term benefits and minimal risks of lifestyle interventions compared to the side effects of pharmacological and surgical options. The review calls for personalized treatment strategies, continuous patient education, and further research to optimize therapeutic outcomes in MASLD management.
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Affiliation(s)
- Hassam Ali
- Department of Gastroenterology, Hepatology & Nutrition, ECU Health Medical Center, Brody School of Medicine, Greenville, NC 27834, USA
- Division of Gastroenterology, Hepatology & Nutrition, East Carolina University, Greenville, NC 27834, USA
| | - Muhammad Shahzil
- Department of Internal Medicine, Weiss Memorial Hospital, Chicago, IL 60640, USA;
| | - Vishali Moond
- Department of Internal Medicine, Saint Peter’s University Hospital, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA
| | - Maria Shahzad
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Abhay Thandavaram
- Department of Internal Medicine, Kamineni Academy of Medical Sciences and Research Centre, Hyderabad 500068, Telangana, India
| | - Alina Sehar
- Department of Internal Medicine, University of Alabama at Birmingham-Huntsville Campus, Huntsville, AL 35801, USA
| | - Haniya Waseem
- Department of Internal Medicine, Advent Health Tampa, Tampa, FL 33613, USA
| | - Taha Siddiqui
- Department of Internal Medicine, Mather Hospital, Hofstra University Zucker School of Medicine, Port Jefferson, NY 11777, USA;
| | - Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66103, USA
| | - Pratik Patel
- Department of Gastroenterology, Mather Hospital, Hofstra University Zucker School of Medicine, Port Jefferson, NY 11777, USA
| | - Hans Tillmann
- Department of Gastroenterology, Hepatology & Nutrition, ECU Health Medical Center, Brody School of Medicine, Greenville, NC 27834, USA
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14
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Ferenc K, Jarmakiewicz-Czaja S, Filip R. What Does Sarcopenia Have to Do with Nonalcoholic Fatty Liver Disease? Life (Basel) 2023; 14:37. [PMID: 38255652 PMCID: PMC10820621 DOI: 10.3390/life14010037] [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: 11/02/2023] [Revised: 12/11/2023] [Accepted: 12/16/2023] [Indexed: 01/24/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. As the second stage of developing steatosis, nonalcoholic hepatitis (NASH) carries the risk of fibrosis, cirrhosis, and hepatocellular carcinoma. Sarcopenia is defined as a condition characterized by a decrease in muscle mass and functional decline. Both NAFLD and sarcopenia are global problems. The pathophysiological mechanisms that link the two entities of the disease are insulin resistance, inflammation, nutritional deficiencies, impairment of myostatin and adiponectin, or physical inactivity. Furthermore, disorders of the gut-liver axis appear to induce the process of developing NAFLD and sarcopenia. The correlations between NAFLD and sarcopenia appear to be bidirectional, so the main objective of the review was to determine the cause-and-effect relationship between the two diseases.
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Affiliation(s)
- Katarzyna Ferenc
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland;
| | | | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland;
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
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15
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Zhang J, Ma S, Zhou W, Feng J, Kang Y, Yang W, Zhang H, Deng F. Genetic polymorphisms of CYP2B6 is a risk of metabolic associated fatty liver disease in Chinese population. Toxicol Appl Pharmacol 2023; 481:116770. [PMID: 37995809 DOI: 10.1016/j.taap.2023.116770] [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: 05/23/2023] [Revised: 10/19/2023] [Accepted: 11/18/2023] [Indexed: 11/25/2023]
Abstract
BACKGROUND The expression and activity of cytochrome P450 2B6 (CYP2B6) may be related to the metabolic associated fat liver disease (MAFLD). Since constitutive androstane receptor (CAR) is a classic transcriptional regulator of CYP2B6, and the single nucleotide polymorphisms (SNPs) of CYP2B6 and CAR are both associated with adverse reactions of efavirenz, we hypothesized that genetic polymorphisms of CAR might also result in additional interindividual variability in CYP2B6. This study was devoted to explore the association between CYP2B6 and CAR SNPs and susceptibility to MAFLD. MATERIALS AND METHODS A total of 590 objects of study (118 with MAFLD and 472 healthy control) between December 2014 and April 2018 were retrospectively enrolled. Twenty-two selected SNPs in CYP2B6 and CAR were genotyped with a custom-designed 48-plex SNP Scan TM® Kit. The frequencies of the alleles, genotypes and genetic models of the variants were compared between the two groups. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. RESULTS The T allele of rs3745274 in CYP2B6 was associated with a decreased risk for MAFLD (OR 0.610; 95% CI: 0.451-0.825, p = 0.001) which was still statistically significant after adjusting with Bonferroni method(p = 0.014) The allele, genotype and genetic model frequencies were similar in the two groups for the other twenty-one SNPs (all P > 0.05). There were no multiplicative or additive interactions between the SNPs. CONCLUSION Our study revealed that rs3745274 variants in CYP2B6 is associated with susceptibility to MAFLD in the Han Chinese population.
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Affiliation(s)
- Jingwei Zhang
- Department of Laboratory Medicine and Department of Blood Transfusion, Chengdu Second People's Hospital, Chengdu, China
| | - Shijie Ma
- Department of Nephrology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Wei Zhou
- Department of Nephrology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Jing Feng
- Department of Traditional Chinese Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yuwei Kang
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Wei Yang
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Heping Zhang
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
| | - Fei Deng
- Department of Nephrology, Sichuan Provincial People's Hospital Jinniu Hospital, Chengdu Jinniu District People's Hospital, Chengdu, China; Department of Nephrology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
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16
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Huang X, Ouyang W, Hu Y, Tang B, He Y, Wu H, Yang P, Yin L, Liu Q, Chen K, Deng J, Li X, Li Y. The effects of weight loss and improved metabolic health status on the risk of non-alcoholic fatty liver disease-results from a prospective cohort in China. Front Nutr 2023; 10:1239996. [PMID: 38094922 PMCID: PMC10718644 DOI: 10.3389/fnut.2023.1239996] [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: 06/14/2023] [Accepted: 11/03/2023] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND The impact of weight loss and/or improved metabolic status on the risk of non-alcoholic fatty liver disease (NAFLD) has yet to be determined. METHODS A total of 35,322 participants without NAFLD were followed. NAFLD risk was compared between consistently metabolically healthy non-obese (MHNO) and non-MHNO who lost weight to become non-obese and/or improved their metabolic health, using Cox proportional hazards and logistic regression models. RESULTS Following 148,186 person-years, 8,409 participants had onset NAFLD, with an incidence rate of 56.75 (95% CI: 55.57, 57.94) per 1,000 person-years. Metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), and metabolically unhealthy non-obese (MUNO) at baseline were associated with increased NAFLD risk, with hazard ratios of 4.48 (95%CI:4.24, 4.73), 8.85 (95%CI:7.95, 9.84), and 10.70 (95%CI:9.73, 11.78). Weight loss and/or metabolic status improvements could significantly reduce NAFLD risk by 79.46 to 41.46%. Specifically, after weight loss from MHO to MHNO, the reduction in NAFLD risk [OR decreased from 12.01 (95%CI:9.40, 15.35) to 4.14 (95%CI:3.08, 5.57)] was greater than that of the MUNO subgroup whose metabolic status improved to MHNO [OR decreased from 5.53 (95%CI:5.15, 5.94) to 2.71 (95%CI:2.50, 3.93)]. In the MUO subgroup, the group with the greatest risk reduction of NAFLD was the weight and metabolic state both improvement group [MUO to MHNO, OR decreased from 22.74 (95%CI:17.61, 29.37) to 4.67 (95%CI:3.05, 7.16)], followed by the weight loss only group [MUO to MUNO, OR decreased to 6.83 (95%CI:4.87, 9.57)], and finally the group with the least and insignificant risk reduction was the metabolic state improvement group [MUO to MHO, OR decreased to 13.38 (95%CI:9.17,19.53)]. NAFLD risk was negatively correlated with the duration of improvement (p < 0.001). CONCLUSION Individuals with non-MHNO were more likely to develop NAFLD than those with consistent MHNO, but metabolic improvements and weight loss can alleviate the risk. Their NAFLD risk was negatively correlated with improvement duration. However, it remained higher than in individuals with consistent MHNO at an average follow-up of 4.2 years.
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Affiliation(s)
- Xin Huang
- Department of Epidemiology, Hunan Normal University School of Medicine, Changsha, China
| | - Wenbin Ouyang
- Department of Epidemiology, Hunan Normal University School of Medicine, Changsha, China
| | - Yang Hu
- Department of Epidemiology, Hunan Normal University School of Medicine, Changsha, China
| | - Bei Tang
- Department of Epidemiology, Hunan Normal University School of Medicine, Changsha, China
| | - Yongmei He
- Department of Health Management, Aerospace Center Hospital, Beijing, China
| | - Hao Wu
- Department of Health Management, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Pingting Yang
- Department of Health Management, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Lu Yin
- Medical Research and Biometrics Center, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qingqi Liu
- Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University, Washington, DC, United States
| | - Kui Chen
- Department of Health Management, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Jing Deng
- Department of Epidemiology, Xiangya School of Public Health, Central South University, Changsha, China
| | - Xiaohui Li
- Department of Pharmacology, Xiangya School of Pharmaceutical Science, Central South University, Changsha, Hunan, China
| | - Ying Li
- Department of Health Management, The Third Xiangya Hospital, Central South University, Changsha, China
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Wu J, Duan C, Yang Y, Wang Z, Tan C, Han C, Hou X. Insights into the liver-eyes connections, from epidemiological, mechanical studies to clinical translation. J Transl Med 2023; 21:712. [PMID: 37817192 PMCID: PMC10566185 DOI: 10.1186/s12967-023-04543-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 09/19/2023] [Indexed: 10/12/2023] Open
Abstract
Maintenance of internal homeostasis is a sophisticated process, during which almost all organs get involved. Liver plays a central role in metabolism and involves in endocrine, immunity, detoxification and storage, and therefore it communicates with distant organs through such mechanisms to regulate pathophysiological processes. Dysfunctional liver is often accompanied by pathological phenotypes of distant organs, including the eyes. Many reviews have focused on crosstalk between the liver and gut, the liver and brain, the liver and heart, the liver and kidney, but with no attention paid to the liver and eyes. In this review, we summarized intimate connections between the liver and the eyes from three aspects. Epidemiologically, we suggest liver-related, potential, protective and risk factors for typical eye disease as well as eye indicators connected with liver status. For molecular mechanism aspect, we elaborate their inter-organ crosstalk from metabolism (glucose, lipid, proteins, vitamin, and mineral), detoxification (ammonia and bilirubin), and immunity (complement and inflammation regulation) aspect. In clinical application part, we emphasize the latest advances in utilizing the liver-eye axis in disease diagnosis and therapy, involving artificial intelligence-deep learning-based novel diagnostic tools for detecting liver disease and adeno-associated viral vector-based gene therapy method for curing blinding eye disease. We aim to focus on and provide novel insights into liver and eyes communications and help resolve existed clinically significant issues.
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Affiliation(s)
- Junhao Wu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Caihan Duan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Yuanfan Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Zhe Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Chen Tan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Chaoqun Han
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
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Gao B, Chen Z, Shi M, Mo Y, Xiao H, Xie Y, Lin M, Chi X. Research landscape and frontiers of non-alcoholic steatohepatitis-associated hepatocellular carcinoma: a bibliometric and visual analysis. Front Pharmacol 2023; 14:1240649. [PMID: 37771721 PMCID: PMC10523561 DOI: 10.3389/fphar.2023.1240649] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 09/04/2023] [Indexed: 09/30/2023] Open
Abstract
Background: Due to the widespread prevalence of caloric excess and sedentary behavior on a global scale, there is a growing body of epidemiological evidence indicating that non-alcoholic steatohepatitis (NASH) has rapidly become a leading aetiology underlying of hepatocellular carcinoma (HCC). In light of the escalating incidence of NASH-associated HCC (NASH-HCC), it is imperative to mitigate the impending burden. While there has been an increase in global awareness regarding this issue, it has yet to be examined from a bibliometric standpoint. Therefore, this study seeks to provide a comprehensive bibliometric analysis to characterize the evolution of this field. Method: The present study utilized the Web of Science Core Collection (WoSCC) to identify publications pertaining to NASH-HCC over the past 2 decades. Employing Vosviewer 1.6.19, CiteSpace 6.2.R2, and the Analysis Platform of Bibliometrics, the study conducted an analysis of various dimensions including the quantity of publications, countries, institutions, journals, authors, co-references, keywords, and trend topics in this field. Results: A comprehensive analysis of 3,679 publications pertaining to NASH-HCC, published between 1 January 2002 and 1 April 2023, was conducted. The field in question experienced a rapid increase in publications, with the United States serving as the central hub. Collaboration between institutions was more extensive than that between countries. Notably, HEPATOLOGY (n = 30,168) emerged as the most impactful journal, and Zobair M. Younossi (n = 10,025) as the most frequently cited author in co-citations. The most commonly cited references were KLEINER DE, 2005, HEPATOLOGY (n = 630), followed by YOUNOSSI ZM, 2016, HEPATOLOGY (n = 493). The author keywords were categorized into three distinct clusters, namely, Cluster 1 (Mechanism), Cluster 2 (Factors), and Cluster 3 (Diagnosis). Analysis of high-frequency co-occurring keywords and topical trends revealed emphasis on molecular mechanisms in current research. "macrophages" and "tumor microenvironment" were active research hotspots at present in this field. Conclusion: A bibliometric analysis was performed for the first time on publications pertaining to non-alcoholic steatohepatitis-hepatocellular carcinoma, uncovering co-research networks, developmental trends, and current research hotspots. The emerging frontiers of this field focused on the macrophages and tumor microenvironment, especially the tumor-associated macrophages, offering a fresh perspective for future research directions.
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Affiliation(s)
- Bowen Gao
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhiheng Chen
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Meijie Shi
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Yousheng Mo
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Huanming Xiao
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Yubao Xie
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Ming Lin
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Xiaoling Chi
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
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19
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Jiang H, Hu Y, Zhang Z, Chen X, Gao J. Identification of metabolic biomarkers associated with nonalcoholic fatty liver disease. Lipids Health Dis 2023; 22:150. [PMID: 37697333 PMCID: PMC10494330 DOI: 10.1186/s12944-023-01911-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 08/28/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease. Metabolism-related genes significantly influence the onset and progression of the disease. Hence, it is necessary to screen metabolism-related biomarkers for the diagnosis and treatment of NAFLD patients. METHODS GSE48452, GSE63067, and GSE89632 datasets including nonalcoholic steatohepatitis (NASH) and healthy controls (HC) analyzed in this study were retrieved from the Gene Expression Omnibus (GEO) database. First, differentially expressed genes (DEGs) between NASH and HC samples were obtained. Next, metabolism-related DEGs (MR-DEGs) were identified by overlapping DEGs and metabolism-related genes (MRG). Further, a protein-protein interaction (PPI) network was developed to show the interaction among MR-DEGs. Subsequently, the "Least absolute shrinkage and selection operator regression" and "Random Forest" algorithms were used to screen metabolism-related genes (MRGs) in patients with NAFLD. Next, immune cell infiltration and gene set enrichment analyses (GSEA) were performed on these metabolism-related genes. Finally, the expression of metabolism-related gene was determined at the transcription level. RESULTS First, 129 DEGs related to NAFLD development were identified among patients with nonalcoholic steatohepatitis (NASH) and healthy control. Next, 18 MR-DEGs were identified using the Venn diagram. Subsequently, four genes, including AMDHD1, FMO1, LPL, and P4HA1, were identified using machine learning algorithms. Moreover, a regulatory network consisting of four genes, 25 microRNAs (miRNAs), and 41 transcription factors (TFs) was constructed. Finally, a significant increase in FMO1 and LPL expression levels and a decrease in AMDHD1 and P4HA1 expression levels were observed in patients in the NASH group compared to the HC group. CONCLUSION Metabolism-related genes associated with NAFLD were identified, containing AMDHD1, FMO1, LPL, and P4HA1, which provide insights into diagnosing and treating patients with NAFLD.
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Affiliation(s)
- Hua Jiang
- Department of Gastroenterology, The Affiffiffiliated YanAn Hospital of Kunming Medical University, Kunming, China
| | - Yang Hu
- Department of Gastroenterology, The Affiffiffiliated YanAn Hospital of Kunming Medical University, Kunming, China
| | - Zhibo Zhang
- Department of Gastroenterology, The Affiffiffiliated YanAn Hospital of Kunming Medical University, Kunming, China
| | - Xujia Chen
- Department of Gastroenterology, The Affiffiffiliated YanAn Hospital of Kunming Medical University, Kunming, China
| | - Jianpeng Gao
- Department of Gastroenterology, The Affiffiffiliated YanAn Hospital of Kunming Medical University, Kunming, China.
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20
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Huang XJ, Yin M, Zhou BQ, Tan XY, Xia YQ, Qin CX. Impact renaming non-alcoholic fatty liver disease to metabolic associated fatty liver disease in prevalence, characteristics and risk factors. World J Hepatol 2023; 15:985-1000. [PMID: 37701916 PMCID: PMC10494565 DOI: 10.4254/wjh.v15.i8.985] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 06/18/2023] [Accepted: 07/17/2023] [Indexed: 08/22/2023] Open
Abstract
BACKGROUND Recently, a group of hepatologists proposed to rename non-alcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) with modified diagnostic criteria. It is important to note, however, that there are some differences between the diagnostic criteria used for NAFLD and MAFLD. Since the research on MAFLD is just beginning, however, evidence on its incidence and prevalence in the general population and in specific subpopulations remains limited. AIM To assess epidemiology of fatty liver in new definition and compare MAFLD with NAFLD. Exploring risk factors of MAFLD individuals. METHODS This was a retrospective, cross-sectional study. A total of 85242 adults were selected from the Chinese health management database in 2017-2022. The data of general information, laboratory indicators, lifestyle management and psychological status were obtained. MAFLD was diagnosed as ultrasound diagnosis of fatty liver and at least one between these three conditions: Overweight/obesity, type 2 diabetes mellitus (T2DM) or metabolic dysregulation. Metabolic factors were not considered in NAFLD diagnosis standard. The clinical characteristics of MAFLD and NAFLD were analysed using descriptive statistics. Continuous variables normally distributed were expressed as means ± SD. Categorical variables were expressed as frequencies and proportions. Binary logistic regression was used to determine risk factors of the MAFLD. RESULTS The prevalence of MAFLD and NAFLD was 40.5% and 31.0%, respectively. The MAFLD or NAFLD population is more likely to be older (M: 47.19 ± 10.82 vs 43.43 ± 11.96; N: 47.72 ± 11.17 vs 43.71 ± 11.66), male (M: 77.21% vs 44.43%; N: 67.90% vs 53.12%) and high body mass index (M: 26.79 ± 2.69 vs 22.44 ± 2.48; N: 26.29 ± 2.84 vs 23.29 ± 3.12) than the non-MAFLD or non-MAFLD population. In multivariate analysis, general information (e.g., ≥ 2 metabolic abnormalities OR = 3.38, (95%CI: 2.99-3.81), P < 0.001; diastolic blood pressure OR = 1.01, (95%CI: 1.00-1.01), P = 0.002), laboratory results [e.g.,total bilirubin (TBIL) OR = 0.98, (95%CI: 0.98-0.99), P < 0.001; serum uric acid(SUA) OR = 1.01, (95%CI: 1.01-1.01), P < 0.001], and lifestyle factors [e.g., drink beverage OR = 0.32, (95%CI: 0.17-0.63), P = 0.001] were influence factors for MAFLD. Our study results offer new insight into potential risk factors associated with fatty liver disease, including SUA, TBIL and creatinine, all of which are related to chronic renal disease (CKD). CONCLUSION MAFLD is more prevalent than NAFLD, with two-fifths of individuals meeting the diagnosis criteria. MAFLD and NAFLD populations have different clinical characteristics. CKD may be related with MAFLD.
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Affiliation(s)
- Xin-Juan Huang
- Xiangya Nursing of School, Central South University, Changsha 410013, Hunan Province, China
| | - Man Yin
- Xiangya Nursing of School, Central South University, Changsha 410013, Hunan Province, China
| | - Bing-Qian Zhou
- Xiangya Nursing of School, Central South University, Changsha 410013, Hunan Province, China
| | - Xin-Yun Tan
- Xiangya Nursing of School, Central South University, Changsha 410013, Hunan Province, China
| | - Yuan-Qin Xia
- School of Medicine, Jishou University, Jishou 416000, Hunan Province, China
| | - Chun-Xiang Qin
- Department of Health Examination Center, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China.
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21
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Bischoff SC, Ockenga J, Eshraghian A, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. Practical guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2023; 42:987-1024. [PMID: 37146466 DOI: 10.1016/j.clnu.2023.03.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 03/27/2023] [Indexed: 05/07/2023]
Abstract
BACKGROUND Patients with chronic gastrointestinal disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean gastrointestinal patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The present practical guideline is intended for clinicians and practitioners in general medicine, gastroenterology, surgery and other obesity management, including dietitians and focuses on obesity care in patients with chronic gastrointestinal diseases. METHODS The present practical guideline is the shortened version of a previously published scientific guideline developed according to the standard operating procedure for ESPEN guidelines. The content has been re-structured and transformed into flow-charts that allow a quick navigation through the text. RESULTS In 100 recommendations (3× A, 33× B, 24 × 0, 40× GPP, all with a consensus grade of 90% or more) care of gastrointestinal patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially metabolic associated liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present practical guideline offers in a condensed way evidence-based advice how to care for patients with chronic gastrointestinal diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; and Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim gGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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22
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [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: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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23
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Semmler G, Datz C, Trauner M. Eating, diet, and nutrition for the treatment of non-alcoholic fatty liver disease. Clin Mol Hepatol 2023; 29:S244-S260. [PMID: 36517001 PMCID: PMC10029946 DOI: 10.3350/cmh.2022.0364] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/06/2022] [Accepted: 12/08/2022] [Indexed: 12/23/2022] Open
Abstract
Nutrition and dietary interventions are a central component in the pathophysiology, but also a cornerstone in the management of patients with non-alcoholic fatty liver disease (NAFLD). Summarizing our rapidly advancing understanding of how our diet influences our metabolism and focusing on specific effects on the liver, we provide a comprehensive overview of dietary concepts to counteract the increasing burden of NAFLD. Specifically, we emphasize the importance of dietary calorie restriction independently of the macronutrient composition together with adherence to a Mediterranean diet low in added fructose and processed meat that seems to exert favorable effects beyond calorie restriction. Also, we discuss intermittent fasting as a type of diet specifically tailored to decrease liver fat content and increase ketogenesis, awaiting future study results in NAFLD. Finally, personalized dietary recommendations could be powerful tools to increase the effectiveness of dietary interventions in patients with NAFLD considering the genetic background and the microbiome, among others.
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Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Christian Datz
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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24
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Bischoff SC, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2022; 41:2364-2405. [PMID: 35970666 DOI: 10.1016/j.clnu.2022.07.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France; Department of Clinical Nutrition, Paul-Brousse-Hospital, Villejuif, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim GGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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25
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Bischoff SC, Barazzoni R, Busetto L, Campmans‐Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon‐Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint European Society for Clinical Nutrition and Metabolism / United European Gastroenterology guideline. United European Gastroenterol J 2022; 10:663-720. [PMID: 35959597 PMCID: PMC9486502 DOI: 10.1002/ueg2.12280] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for European Society for Clinical Nutrition and Metabolism guidelines, following the Scottish Intercollegiate Guidelines Network grading system (A, B, 0, and good practice point [GPP]). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational SciencesUniversity of TriesteTriesteItaly
| | - Luca Busetto
- Department of MedicineUniversity of PadovaPadovaItaly
| | - Marjo Campmans‐Kuijpers
- Department of Gastroenterology and HepatologyUniversity Medical Centre GroningenGroningenThe Netherlands
| | - Vincenzo Cardinale
- Department of Medico‐Surgical Sciences and BiotechnologiesSapienza University of RomeRomeItaly
| | - Irit Chermesh
- Department of GastroenterologyRambam Health Care CampusAffiliated with Technion‐Israel Institute of TechnologyHaifaIsrael
| | - Ahad Eshraghian
- Department of Gastroenterology and HepatologyAvicenna HospitalShirazIran
| | - Haluk Tarik Kani
- Department of GastroenterologyMarmara UniversitySchool of MedicineIstanbulTurkey
| | - Wafaa Khannoussi
- Hepato‐Gastroenterology DepartmentMohammed VI University HospitalOujdaMorocco
- Laboratoire de Recherche des Maladies Digestives (LARMAD)Mohammed the First UniversityOujdaMorocco
| | - Laurence Lacaze
- Department of NutritionRennes HospitalRennesFrance
- Department of general surgeryMantes‐la‐Jolie HospitalFrance
- Department of clinical nutritionPaul Brousse‐Hospital, VillejuifFrance
| | - Miguel Léon‐Sanz
- Department of Endocrinology and NutritionUniversity Hospital Doce de OctubreMedical SchoolUniversity ComplutenseMadridSpain
| | - Juan M. Mendive
- La Mina Primary Care Academic Health Centre. Catalan Institute of Health (ICS)University of BarcelonaBarcelonaSpain
| | - Michael W. Müller
- Department of General and Visceral SurgeryRegionale Kliniken HoldingKliniken Ludwigsburg‐Bietigheim gGmbHBietigheim‐BissingenGermany
| | - Johann Ockenga
- Medizinische Klinik IIKlinikum Bremen‐MitteBremenGermany
| | - Frank Tacke
- Department of Hepatology & GastroenterologyCharité Universitätsmedizin BerlinCampus Virchow‐Klinikum and Campus Charité MitteBerlinGermany
| | - Anders Thorell
- Department of Clinical ScienceDanderyds HospitalKarolinska InstitutetStockholmSweden
- Department of SurgeryErsta HospitalStockholmSweden
| | - Darija Vranesic Bender
- Department of Internal MedicineUnit of Clinical NutritionUniversity Hospital Centre ZagrebZagrebCroatia
| | - Arved Weimann
- Department of General, Visceral and Oncological SurgerySt. George HospitalLeipzigGermany
| | - Cristina Cuerda
- Departamento de MedicinaUniversidad Complutense de MadridNutrition UnitHospital General Universitario Gregorio MarañónMadridSpain
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Ristic-Medic D, Bajerska J, Vucic V. Crosstalk between dietary patterns, obesity and nonalcoholic fatty liver disease. World J Gastroenterol 2022; 28:3314-3333. [PMID: 36158263 PMCID: PMC9346467 DOI: 10.3748/wjg.v28.i27.3314] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 05/03/2022] [Accepted: 06/18/2022] [Indexed: 02/06/2023] Open
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising worldwide, paralleling the epidemic of obesity. The liver is a key organ for the metabolism of proteins, fats and carbohydrates. Various types of fats and carbohydrates in isocaloric diets differently influence fat accumulation in the liver parenchyma. Therefore, nutrition can manage hepatic and cardiometabolic complications of NAFLD. Even moderately reduced caloric intake, which leads to a weight loss of 5%-10% of initial body weight, is effective in improving liver steatosis and surrogate markers of liver disease status. Among dietary patterns, the Mediterranean diet mostly prevents the onset of NAFLD. Furthermore, this diet is also the most recommended for the treatment of NAFLD patients. However, clinical trials based on the dietary interventions in NAFLD patients are sparse. Since there are only a few studies examining dietary interventions in clinically advanced stages of NAFLD, such as active and fibrotic steatohepatitis, the optimal diet for patients in these stages of the disease must still be determined. In this narrative review, we aimed to critically summarize the associations between different dietary patterns, obesity and prevention/risk for NAFLD, to describe specific dietary interventions' impacts on liver steatosis in adults with NAFLD and to provide an updated overview of dietary recommendations that clinicians potentially need to apply in their daily practice.
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Affiliation(s)
- Danijela Ristic-Medic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic Serbia, Belgrade PO Box 102, Serbia
| | - Joanna Bajerska
- Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań 60-624, Poland
| | - Vesna Vucic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic Serbia, Belgrade PO Box 102, Serbia
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27
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Hu X, Fan J, Ma Q, Han L, Cao Z, Xu C, Luan J, Jing G, Nan Y, Wu T, Zhang Y, Wang H, Zhang Y, Ju D. A novel nanobody-heavy chain antibody against Angiopoietin-like protein 3 reduces plasma lipids and relieves nonalcoholic fatty liver disease. J Nanobiotechnology 2022; 20:237. [PMID: 35590366 PMCID: PMC9118633 DOI: 10.1186/s12951-022-01456-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 05/07/2022] [Indexed: 11/29/2022] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease mainly on account of hypercholesterolemia and may progress to cirrhosis and hepatocellular carcinoma. The discovery of effective therapy for NAFLD is an essential unmet need. Angiopoietin-like protein 3 (ANGPTL3), a critical lipid metabolism regulator, resulted in increased blood lipids and was elevated in NAFLD. Here, we developed a nanobody-heavy chain antibody (VHH-Fc) to inhibit ANGPTL3 for NAFLD treatment. Results In this study, we retrieved an anti-ANGPTL3 VHH and Fc fusion protein, C44-Fc, which exhibited high affinities to ANGPTL3 proteins and rescued ANGPLT3-mediated inhibition of lipoprotein lipase (LPL) activity. The C44-Fc bound a distinctive epitope within ANGPTL3 when compared with the approved evinacumab, and showed higher expression yield. Meanwhile, C44-Fc had significant reduction of the triglyceride (~ 44.2%), total cholesterol (~ 36.6%) and LDL-cholesterol (~ 54.4%) in hypercholesterolemic mice and ameliorated hepatic lipid accumulation and liver injury in NAFLD mice model. Conclusions We discovered a VHH-Fc fusion protein with high affinity to ANGPTL3, strong stability and also alleviated the progression of NAFLD, which might offer a promising therapy for NAFLD. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12951-022-01456-z.
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Affiliation(s)
- Xiaozhi Hu
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Jiajun Fan
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Qianqian Ma
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China.,National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, 201203, China
| | - Lei Han
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Zhonglian Cao
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Caili Xu
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Jingyun Luan
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China.,Ben May Department of Cancer Research, The University of Chicago, Chicago, IL, 60615, USA
| | - Guangjun Jing
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Yanyang Nan
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Tao Wu
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Yuting Zhang
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Hanqi Wang
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Yuanzhen Zhang
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China
| | - Dianwen Ju
- School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China.
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Geng Q, Zhang P, Liu X, Xue L. Effect of berberine and bicyclol on Chinese patients with non-alcoholic fatty liver disease: a retrospective study. Postgrad Med 2022; 134:507-515. [PMID: 35382695 DOI: 10.1080/00325481.2022.2063568] [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] [Indexed: 10/18/2022]
Abstract
OBJECTIVES To compare the effect of berberine and bicyclol on patients with non-alcoholic fatty liver disease (NAFLD). METHODS Chinese non-alcoholic and non-viral hepatitis patients with a hepatic lipid content > 13% and non-alcoholic fatty liver disease activity score (NAS) ≥ 2 were treated with 500 mg berberine thrice daily, together with dietary modification (low-fat diet) and Tai Chi exercise for 4 months (BT cohort; n = 112), or 25 mg bicyclol thrice daily plus dietary modification and Tai Chi exercise for 4 months (CT cohort, n = 145), or dietary modification and Tai Chi exercise for 4 months (DT cohort, n = 128). RESULTS Patients in the BT and the CT cohorts had improved anthropometric measurements (weight, height, body mass index, and waist-to-hip ratio), biochemical parameters (blood sugar, lipid profile, and liver functions tests), liver/spleen computed tomography findings, and liver biopsy results after 4 months of intervention (p < 0.05 for all). Bicyclol decreased the NAS in the CT cohort to a significantly greater degree than berberine in the BT cohort (p < 0.0001, q = 3.879). Patients in the DT cohort had reduced body mass index and waist-to-hip ratio (p < 0.05 for both). During the 4-month intervention, patients in the BT cohort had abdominal distension, mild diarrhea, constipation, nausea, and dyspepsia; patients in the CT cohort had dizziness and abdominal distension. CONCLUSIONS Berberine or bicyclol plus dietary modification and Tai Chi exercise could control NAFLD without serious adverse effects. Dietary modification and Tai Chi exercise alone for 4 months are insufficient for the management of NAFLD. It is possible to reduce body weight by administering berberine or bicyclol.
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Affiliation(s)
- Qianwen Geng
- Department of Gastroenterology, General Hospital of Tisco, the Sixth Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Peng Zhang
- Department of Gastroenterology, General Hospital of Tisco, the Sixth Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaohua Liu
- Department of Gastroenterology, General Hospital of Tisco, the Sixth Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Linglong Xue
- Department of Gastroenterology, General Hospital of Tisco, the Sixth Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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Xie ZQ, Li HX, Tan WL, Yang L, Ma XW, Li WX, Wang QB, Shang CZ, Chen YJ. Association of Serum Vitamin C With NAFLD and MAFLD Among Adults in the United States. Front Nutr 2022; 8:795391. [PMID: 35187020 PMCID: PMC8854786 DOI: 10.3389/fnut.2021.795391] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/15/2021] [Indexed: 01/01/2023] Open
Abstract
Background and Aims Despite the remarkable progress of metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), the disease remains poorly improved. Since increased oxidative stress and inflammation contribute to the initiation and progression of fatty liver disorders, vitamin C (VC), an antioxidant agent, might be a suitable treatment option for MAFLD. However, the lack of clinically confirmed benefits makes clinicians challenging to recommend antioxidant supplements for MAFLD individuals. Methods Herein, the nationally representative National Health and Nutrition Examination Survey 2017–2018 data were collected to evaluate the potential association between the serum VC levels with the risk of different categories of NALFD and the newly proposed MAFLD terminology. Hepatic steatosis was defined as controlled attenuated parameter scores ≥ 263 dB/m, whereas liver fibrosis (LF) status was defined as F0–F4, with the cutoff values of median liver stiffness being 6.3, 8.3, 10.5, and 12.5 (KPa), respectively. A cross-sectional analysis was performed to calculate the odds rate and determine the potential beneficial effects of VC. Results A total of 4,494 participants aged more than 18 years and conducted transient elastography examinations were included. Our findings demonstrated that participants with increased serum VC status were more likely to be female predominant, more educated, and moderate drinkers. Interestingly, female participants tended to have a lower prevalence of NAFLD, MAFLD, LF, and liver cirrhosis (LC) after stratification by gender. Moreover, our results revealed that participants from the quartile three group (quartile 3: 50.5–67.0 μmol/L) experienced a slightly lower risk of MAFLD than the risk of NAFLD. Of note, the serum concentration of VC (quartile 2: 30.9–50.5 μmol/L) inversely associated with LF and LC was lower than the serum VC level (quartile 3) associated with NAFLD and MAFLD. Notably, individuals from the quartile 3 group experienced a statistically significant 32.5, 42.0, 45.7, and 71% decrease in risk of NAFLD, MAFLD, LF, and LC, respectively. Conclusion In summary, our findings suggested an inverse association between serum VC levels and NAFLD, MAFLD, LF, or LC. Additionally, adjustment of VC supplementation according to age, gender, and ethnicity may be a promising candidate for these diseases.
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Affiliation(s)
- Zhi-Qin Xie
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hong-Xia Li
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wen-Liang Tan
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lei Yang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiao-Wu Ma
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wen-Xin Li
- Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Qing-Bin Wang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chang-Zhen Shang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Chang-Zhen Shang
| | - Ya-Jin Chen
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Ya-Jin Chen
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Pearson A, Dujardin P, d'Alteroche L, Patat F, Scotto B, Dujardin F, Bastard C, Miette V, Sandrin L, Remenieras J. Vibration controlled transient elastography for non‐invasive evaluation of liver steatosis. Med Phys 2022; 49:1507-1521. [PMID: 35094409 PMCID: PMC9401907 DOI: 10.1002/mp.15484] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 01/06/2022] [Accepted: 01/07/2022] [Indexed: 11/07/2022] Open
Affiliation(s)
- Arthur Pearson
- Radiology department University Hospital of Tours Tours 37000 France
- CIC Inserm 1415 University Hospital of Tours Tours 37000 France
| | | | - Louis d'Alteroche
- Hepatology department University Hospital of Tours Tours 37000 France
| | - Frédéric Patat
- Radiology department University Hospital of Tours Tours 37000 France
- CIC Inserm 1415 University Hospital of Tours Tours 37000 France
- UMR Inserm 1253, iBrain François Rabelais University of Tours Tours 37000 France
| | - Béatrice Scotto
- Radiology department University Hospital of Tours Tours 37000 France
| | - Fanny Dujardin
- Pathology department University Hospital of Tours Tours 37000 France
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Semmler G, Datz C, Reiberger T, Trauner M. Diet and exercise in NAFLD/NASH: Beyond the obvious. Liver Int 2021; 41:2249-2268. [PMID: 34328248 PMCID: PMC9292198 DOI: 10.1111/liv.15024] [Citation(s) in RCA: 103] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/06/2021] [Accepted: 07/10/2021] [Indexed: 12/12/2022]
Abstract
Lifestyle represents the most relevant factor for non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of the metabolic syndrome. Although a tremendous body of clinical and preclinical data on the effectiveness of dietary and lifestyle interventions exist, the complexity of this topic makes firm and evidence-based clinical recommendations for nutrition and exercise in NAFLD difficult. The aim of this review is to guide readers through the labyrinth of recent scientific findings on diet and exercise in NAFLD and non-alcoholic steatohepatitis (NASH), summarizing "obvious" findings in a holistic manner and simultaneously highlighting stimulating aspects of clinical and translational research "beyond the obvious". Specifically, the importance of calorie restriction regardless of dietary composition and evidence from low-carbohydrate diets to target the incidence and severity of NAFLD are discussed. The aspect of ketogenesis-potentially achieved via intermittent calorie restriction-seems to be a central aspect of these diets warranting further investigation. Interactions of diet and exercise with the gut microbiota and the individual genetic background need to be comprehensively understood in order to develop personalized dietary concepts and exercise strategies for patients with NAFLD/NASH.
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Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Christian Datz
- Department of Internal MedicineGeneral Hospital OberndorfTeaching Hospital of the Paracelsus Medical University SalzburgSalzburgAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
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Abstract
Introduction: Oxidative stress underlies the pathophysiology of various etiologies of chronic liver disease and contributes to the development of hepatocarcinogenesis.Areas covered: This review focuses on the impact of oxidative stress in various etiologies of chronic liver disease such as alcoholic liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection. The efficacy of antioxidants in laboratory, animal, and clinical studies in chronic liver disease is also reviewed.Expert opinion: Currently, there are limited targeted pharmacotherapeutics for NASH and no pharmacotherapeutics for ALD and antioxidant supplementation may be useful in these conditions to improve liver function and reverse fibrosis. Antioxidants may also be used in patients with HBV or HCV infection to supplement antiviral therapies. Specific genotypes of antioxidant and prooxidant genes render patients more susceptible to liver cirrhosis and hepatocellular carcinoma while other individual characteristics like age, genotype, and metabolomic profiling can influence the efficacy of antioxidants on CLD. More research needs to be done to establish the safety, efficacy, and dosage of antioxidants and to establish the ideal patient profile that will benefit the most from antioxidant treatment.
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Affiliation(s)
- Sophia Seen
- Tan Tock Seng Hospital, Singapore, Singapore
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33
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Hunter AK, Lin HC. Review of Clinical Guidelines in the Diagnosis of Pediatric Nonalcoholic Fatty Liver Disease. Clin Liver Dis (Hoboken) 2021; 18:40-44. [PMID: 34484704 PMCID: PMC8405050 DOI: 10.1002/cld.1094] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 12/06/2020] [Accepted: 12/22/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Anna K. Hunter
- Division of GastroenterologyDoernbecher Children’s HospitalPortlandOR,Department of PediatricsOregon Health & Science UniversityPortlandOR
| | - Henry C. Lin
- Division of GastroenterologyDoernbecher Children’s HospitalPortlandOR,Department of PediatricsOregon Health & Science UniversityPortlandOR
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Kang SH, Lee HW, Yoo JJ, Cho Y, Kim SU, Lee TH, Jang BK, Kim SG, Ahn SB, Kim H, Jun DW, Choi JI, Song DS, Kim W, Jeong SW, Kim MY, Koh H, Jeong S, Lee JW, Cho YK. KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease. Clin Mol Hepatol 2021; 27:363-401. [PMID: 34154309 PMCID: PMC8273632 DOI: 10.3350/cmh.2021.0178] [Citation(s) in RCA: 166] [Impact Index Per Article: 41.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Affiliation(s)
- Seong Hee Kang
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, SoonChunHyang University Bucheon Hospital, Bucheon, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul Korea
| | - Tae Hee Lee
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, SoonChunHyang University Bucheon Hospital, Bucheon, Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Joon-Il Choi
- Department of Radiology, Seoul St.Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Do Seon Song
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hong Koh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea
| | - Sujin Jeong
- Division of Pediatric Gastroenterology Hepatology and Nutrition, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Jin-Woo Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Yong Kyun Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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Fraenkel L, Bathon JM, England BR, St.Clair EW, Arayssi T, Carandang K, Deane KD, Genovese M, Huston KK, Kerr G, Kremer J, Nakamura MC, Russell LA, Singh JA, Smith BJ, Sparks JA, Venkatachalam S, Weinblatt ME, Al-Gibbawi M, Baker JF, Barbour KE, Barton JL, Cappelli L, Chamseddine F, George M, Johnson SR, Kahale L, Karam BS, Khamis AM, Navarro-Millán I, Mirza R, Schwab P, Singh N, Turgunbaev M, Turner AS, Yaacoub S, Akl EA. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 2021; 73:924-939. [PMID: 34101387 PMCID: PMC9273041 DOI: 10.1002/acr.24596] [Citation(s) in RCA: 518] [Impact Index Per Article: 129.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 03/15/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.
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Affiliation(s)
- Liana Fraenkel
- Berkshire Medical Center, Pittsfield, Massachusetts, and Yale University School of Medicine, New Haven, Connecticut
| | - Joan M. Bathon
- Columbia University Irving Medical Center, New York Presbyterian Hospital, New York, New York
| | - Bryant R. England
- University of Nebraska Medical Center and VA Nebraska–Western Iowa Health Care System, Omaha, Nebraska
| | | | | | | | | | - Mark Genovese
- Stanford University Medical Center, Palo Alto, California
| | - Kent Kwas Huston
- The Center for Rheumatic Disease/Allergy and Immunology, Kansas City, Missouri
| | - Gail Kerr
- Veterans Affairs Medical Center, Georgetown and Howard University, Washington, DC
| | - Joel Kremer
- Albany Medical College and The Center for Rheumatology, Albany, New York
| | | | | | - Jasvinder A. Singh
- University of Alabama at Birmingham and Birmingham Veterans Affairs Medical Center, Birmingham, Alabama
| | - Benjamin J. Smith
- State University College of Medicine School of Physician Assistant Practice, Tallahassee
| | - Jeffrey A. Sparks
- Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
| | | | | | | | - Joshua F. Baker
- Corporal Michael J. Crescenz VA Medical Center and the University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Jennifer L. Barton
- Oregon Health & Science University and VA Portland Health Care System, Portland, Oregon
| | | | | | | | - Sindhu R. Johnson
- Toronto Western Hospital, Mount Sinai Hospital, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Lara Kahale
- American University of Beirut, Beirut, Lebanon
| | | | | | | | - Reza Mirza
- University of Toronto, Toronto, Ontario, Canada
| | - Pascale Schwab
- Oregon Health & Science University and VA Portland Health Care System, Portland, Oregon
| | | | | | | | | | - Elie A. Akl
- American University of Beirut, Beirut, Lebanon
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Fraenkel L, Bathon JM, England BR, St Clair EW, Arayssi T, Carandang K, Deane KD, Genovese M, Huston KK, Kerr G, Kremer J, Nakamura MC, Russell LA, Singh JA, Smith BJ, Sparks JA, Venkatachalam S, Weinblatt ME, Al-Gibbawi M, Baker JF, Barbour KE, Barton JL, Cappelli L, Chamseddine F, George M, Johnson SR, Kahale L, Karam BS, Khamis AM, Navarro-Millán I, Mirza R, Schwab P, Singh N, Turgunbaev M, Turner AS, Yaacoub S, Akl EA. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol 2021; 73:1108-1123. [PMID: 34101376 DOI: 10.1002/art.41752] [Citation(s) in RCA: 431] [Impact Index Per Article: 107.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 03/15/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.
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Affiliation(s)
- Liana Fraenkel
- Berkshire Medical Center, Pittsfield, Massachusetts, and Yale University School of Medicine, New Haven, Connecticut, United States
| | - Joan M Bathon
- Columbia University Irving Medical Center, New York Presbyterian Hospital, New York, New York, United States
| | - Bryant R England
- University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, United States
| | | | | | | | | | - Mark Genovese
- Stanford University Medical Center, Palo Alto, California, United States
| | - Kent Kwas Huston
- The Center for Rheumatic Disease/Allergy and Immunology, Kansas City, Missouri, United States
| | - Gail Kerr
- Veterans Affairs Medical Center, Georgetown and Howard University, Washington, DC, United States
| | - Joel Kremer
- Albany Medical College and The Center for Rheumatology, Albany, New York, United States
| | | | - Linda A Russell
- Hospital for Special Surgery, New York, New York, United States
| | - Jasvinder A Singh
- University of Alabama at Birmingham and Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, United States
| | - Benjamin J Smith
- Florida State University College of Medicine School of Physician Assistant Practice, Tallahassee
| | - Jeffrey A Sparks
- Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
| | | | - Michael E Weinblatt
- Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
| | | | - Joshua F Baker
- Corporal Michael J. Crescenz VA Medical Center and the University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Kamil E Barbour
- Centers for Disease Control and Prevention, Atlanta, Georgia, United States
| | - Jennifer L Barton
- Oregon Health & Science University and VA Portland Health Care System, Portland, Oregon, United States
| | - Laura Cappelli
- Johns Hopkins Medicine, Baltimore, Maryland, United States
| | | | | | - Sindhu R Johnson
- Toronto Western Hospital, Mount Sinai Hospital, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Lara Kahale
- American University of Beirut, Beirut, Lebanon
| | | | | | | | - Reza Mirza
- University of Toronto, Toronto, Ontario, Canada
| | - Pascale Schwab
- Oregon Health & Science University and VA Portland Health Care System, Portland, Oregon, United States
| | | | - Marat Turgunbaev
- American College of Rheumatology, Atlanta, Georgia, United States
| | - Amy S Turner
- American College of Rheumatology, Atlanta, Georgia, United States
| | | | - Elie A Akl
- American University of Beirut, Beirut, Lebanon
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Ríos León R, Sánchez Rodríguez E, Martínez Ortega A, Rodríguez de Santiago E, Marcos Carrasco N, Graus Morales J, Rodríguez Gandía MÁ, Lledó Navarro JL, Gea Rodríguez F, Nuño Vázquez Garza JM, Albillos Martínez A, García González M. Characteristics and outcome of incidental hepatocellular carcinoma after liver transplantation: a cohort study. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 114:219-225. [PMID: 33733806 DOI: 10.17235/reed.2021.7744/2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION Despite advances in imaging diagnostic modalities, hepatocellular carcinoma is sometimes incidentally diagnosed on histological examination of the liver explant. Our objectives were: 1) To compare the characteristics between incidental and known hepatocellular carcinoma and 2) To estimate survival and tumor recurrence after liver transplantation. MATERIAL AND METHODS Retrospective, single-center study. The inclusion criteria were 1) cirrhotic patients, age≥18 years, 2) Liver transplantation between 1998 and 2018, and 3) hepatocellular carcinoma diagnosed on the histopathologic examination of the explanted liver. Cholangiocarcinoma and patients with early retransplantation were excluded. Multivariate analysis was performed using binomial logistic regression to assess the factors associated incidental hepatocellular carcinoma. Kaplan-Meier curves were plotted to explore the impact on overall survival and recurrence free survival. RESULTS 269 patients were enrolled. The prevalence of incidental hepatocellular carcinoma was 4.18% (95% CI: 2.89-6.01%) of all liver transplants performed in cirrhotic patients. The median diameter of the main nodule was smaller in incidental hepatocellular carcinoma (20 vs 27 mm, p=0.004) although they were more likely to be beyond the Up-to-Seven criteria on explant examination (22.2% vs 7.5%, p=0.001), showing no differences in any other histological features. No differences were found in overall survival rates (incidental 70.2% vs 70.4%, p=0.87) nor recurrence-free survival (incidental 100% vs 83.8%, p=0.07) at 5 years. CONCLUSION Incidental hepatocellular carcinoma has a smaller size and is more frequently found to be beyond the Up-to-Seven criteria. However, no differences were found in overall survival rates nor recurrence-free survival, although there was no tumor recurrence in incidental hepatocellular carcinoma group.
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Affiliation(s)
- Raquel Ríos León
- Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
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Vadarlis A, Antza C, Bakaloudi DR, Doundoulakis I, Kalopitas G, Samara M, Dardavessis T, Maris T, Chourdakis M. Systematic review with meta-analysis: The effect of vitamin E supplementation in adult patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2021; 36:311-319. [PMID: 32810309 DOI: 10.1111/jgh.15221] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 08/16/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Νon-alcoholic fatty liver disease (NAFLD) is estimated to be the most common cause of end-stage liver disease in the next years. Vitamin E has shown beneficial effects as a possible "scavenger" of oxidative stress products, which play a major role in pathogenesis of the disease. The purpose of the present meta-analysis is to investigate the effects of vitamin E supplementation in biochemical and histological parameters in adult patients with NAFLD. METHODS Literature search was performed in major electronic databases (MEDLINE, CENTRAL, and Embase) up to June 2020 for randomized clinical trials, which examined vitamin E versus placebo treatment in adults with NAFLD. Changes in liver enzymes were considered as primary outcomes while changes in histological, biochemical, and metabolic parameters as secondary. Quality of evidence was assessed through risk of bias according to the Cochrane risk of bias tool. RESULTS Eight studies were included in qualitative analysis and seven in quantitative analysis. Vitamin E reduced the values of liver enzymes compared with placebo (-7.37 IU/L, 95% confidence interval: -10.11 to -4.64 for alanine aminotransferase, and -5.71 IU/L, 95% confidence interval: -9.49 to -1.93 for aspartate aminotransferase). Additionally, vitamin E improved statistically significantly liver pathology in every individual histological parameter as well as low-density lipoprotein cholesterol, fasting blood glucose, and serum leptin values. CONCLUSIONS Vitamin E can improve biochemical and histological characteristics of NAFLD patients, especially of non-alcoholic steatohepatitis patients. The results indicate that vitamin E could be a promising choice and be considered as a treatment option in patients with NAFLD.
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Affiliation(s)
- Andreas Vadarlis
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.,Department of Gastroenterology and Hepatology, General Hospital of Thessaloniki "G. Papanikolaou", Thessaloniki, Greece
| | - Christina Antza
- 3rd Department of Internal Medicine, G. N Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitra Rafailia Bakaloudi
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ioannis Doundoulakis
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Georgios Kalopitas
- Division of Gastroenterology and Hepatology, 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Myrto Samara
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Theodoros Dardavessis
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Theofanis Maris
- Department of Gastroenterology and Hepatology, General Hospital of Thessaloniki "G. Papanikolaou", Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Fischer R, Kontermann RE, Pfizenmaier K. Selective Targeting of TNF Receptors as a Novel Therapeutic Approach. Front Cell Dev Biol 2020; 8:401. [PMID: 32528961 PMCID: PMC7264106 DOI: 10.3389/fcell.2020.00401] [Citation(s) in RCA: 144] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 05/01/2020] [Indexed: 12/14/2022] Open
Abstract
Tumor necrosis factor (TNF) is a central regulator of immunity. Due to its dominant pro-inflammatory effects, drugs that neutralize TNF were developed and are clinically used to treat inflammatory and autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. However, despite their clinical success the use of anti-TNF drugs is limited, in part due to unwanted, severe side effects and in some diseases its use even is contraindicative. With gaining knowledge about the signaling mechanisms of TNF and the differential role of the two TNF receptors (TNFR), alternative therapeutic concepts based on receptor selective intervention have led to the development of novel protein therapeutics targeting TNFR1 with antagonists and TNFR2 with agonists. These antibodies and bio-engineered ligands are currently in preclinical and early clinical stages of development. Preclinical data obtained in different disease models show that selective targeting of TNFRs has therapeutic potential and may be superior to global TNF blockade in several disease indications.
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Affiliation(s)
- Roman Fischer
- Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany
| | - Roland E Kontermann
- Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany
| | - Klaus Pfizenmaier
- Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany
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Miller EF. Nutrition Management Strategies for Nonalcoholic Fatty Liver Disease: Treatment and Prevention. Clin Liver Dis (Hoboken) 2020; 15:144-148. [PMID: 32395240 PMCID: PMC7206319 DOI: 10.1002/cld.918] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 12/28/2019] [Indexed: 02/06/2023] Open
Abstract
http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-4-reading-miller a video presentation of this article.
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Affiliation(s)
- Evelyn F. Miller
- Food and Nutrition ServicesUniversity of California Davis HealthSacramentoCA
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41
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Swain MG, Ramji A, Patel K, Sebastiani G, Shaheen AA, Tam E, Marotta P, Elkhashab M, Bajaj HS, Estes C, Razavi H. Burden of nonalcoholic fatty liver disease in Canada, 2019-2030: a modelling study. CMAJ Open 2020; 8:E429-E436. [PMID: 32518095 PMCID: PMC7286622 DOI: 10.9778/cmajo.20190212] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a growing proportion of liver disease cases, and there is a need to better understand future disease burden. We used a modelling framework to forecast the burden of disease of NAFLD and NASH for Canada. METHODS We used a Markov model to forecast fibrosis progression from stage F0 (no fibrosis) to stage F4 (compensated cirrhosis) and subsequent progression to decompensated cirrhosis, hepatocellular carcinoma, liver transplantation and liver-related death among Canadians with NAFLD from 2019 to 2030. We used historical trends for obesity prevalence among adults to estimate longitudinal changes in the number of incident NAFLD cases. RESULTS The model projected that the number of NAFLD cases would increase by 20% between 2019 and 2030, from an estimated 7 757 000 cases to 9 305 000 cases. Increases in advanced fibrosis cases were relatively greater, as the number of model-estimated prevalent stage F3 cases would increase by 65%, to 357 000, and that of prevalent stage F4 cases would increase by 95%, to 195 000. Estimated incident cases of hepatocellular carcinoma and decompensated cirrhosis would increase by up to 95%, and the number of annual NAFLD-related deaths would double, to 5600. INTERPRETATION Increasing rates of obesity translate into increasing NAFLD-related cases of cirrhosis and hepatocellular carcinoma and related mortality. Prevention efforts should be aimed at reducing the incidence of NAFLD and slowing fibrosis progression among those already affected.
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Affiliation(s)
- Mark G Swain
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
| | - Alnoor Ramji
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
| | - Keyur Patel
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
| | - Abdel Aziz Shaheen
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
| | - Edward Tam
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
| | - Paul Marotta
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
| | - Magdy Elkhashab
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
| | - Harpreet S Bajaj
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
| | - Chris Estes
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo.
| | - Homie Razavi
- Division of Gastroenterology and Hepatology (Swain, Shaheen), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Toronto Centre for Liver Disease (Patel), University Hospital Network, Toronto, Ont.; Division of Gastroenterology and Hepatology (Sebastiani), McGill University Health Centre, Montréal, Que.; LAIR Centre (Tam), Vancouver, BC; Division of Gastroenterology (Marotta), Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.; Toronto Liver Centre (Elkhashab), Toronto, Ont.; LMC Diabetes and Endocrinology Brampton (Bajaj), Brampton, Ont.; Leadership Sinai Centre for Diabetes (Bajaj), Mount Sinai Hospital, Toronto, Ont.; Center for Disease Analysis Foundation (Estes, Razavi), Lafayette, Colo
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