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Zafar Y, Sohail MU, Saad M, Ahmed SZ, Sohail MO, Zafar J, Lirette S, Singal A. eHealth interventions and patients with metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis. BMJ Open Gastroenterol 2025; 12:e001670. [PMID: 40204429 PMCID: PMC11987102 DOI: 10.1136/bmjgast-2024-001670] [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: 11/13/2024] [Accepted: 03/11/2025] [Indexed: 04/11/2025] Open
Abstract
OBJECTIVE Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern, with increasing mortality rates driven by the obesity pandemic. Weight loss has been shown to improve MASLD outcomes, yet the effectiveness of eHealth interventions in MASLD management remains uncertain. We aimed to evaluate the effectiveness of eHealth interventions compared with standard care in improving health outcomes among patients with MASLD. DESIGN A systematic review and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES Relevant studies were retrieved from PubMed, Cochrane Central and Embase databases from inception to 26 April 2024. ELIGIBILITY CRITERIA Only double-arm clinical trials involving human participants diagnosed with MASLD were included. Eligible studies were limited to those published in English. DATA EXTRACTION AND SYNTHESIS eHealth interventions-including internet-based platforms, smartwatches, telephone follow-ups and mobile applications for dietary and exercise modifications-were compared against traditional intervention methods. The primary outcomes assessed were changes in body weight, abdominal/waist circumference, aspartate aminotransferase (AST) and alanine transaminase (ALT). Secondary outcomes were changes in body mass index (BMI), diastolic blood pressure, systolic blood pressure, MASLD fibrosis score, high-density lipoprotein, gamma-glutamyl transferase and triglycerides. RESULTS 11 studies met the inclusion criteria, of which 10 provided relevant outcomes and were included. The mean age of participants across the studies ranged from 39.3 to 57.9 years, with intervention durations spanning 3 to 24 months. Our results indicate significant improvements with eHealth interventions compared with control comparators, including reductions in AST (standardised mean difference (SMD): -0.35 (95% CI -0.61, -0.10); p<0.05), ALT (SMD: -0.38 (95% CI -0.65, -0.11); p<0.05), weight loss (SMD: -0.38 (95% CI -0.60, -0.17); p<0.05) and BMI (SMD: -0.37 (95% CI -0.54, -0.21); p<0.05). CONCLUSIONS The utilisation of eHealth interventions showed significant improvements in outcomes related to AST, ALT, abdominal circumference, weight loss and BMI. However, future studies with larger sample sizes and longer follow-ups are warranted to assess the sustainability of these outcomes.
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Affiliation(s)
- Yousuf Zafar
- Department of Medicine, University of Mississippi University Hospital, Jackson, Mississippi, USA
| | | | - Muhammad Saad
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Syed Zaeem Ahmed
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | | | - Javaid Zafar
- Department of Medicine, University of Mississippi University Hospital, Jackson, Mississippi, USA
| | - Seth Lirette
- Department of Data Science, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Ashwani Singal
- Division of Gastroenterology and Hepatology, University of Louisville School of Medicine; Trager Transplant Center and Jewish Hospital, Louisville, Kentucky, USA
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El-Sayed SM, El-Sayed GA, Mansour M A, Haridy Ahmed E, Kamar SA. A comparative study on the effect of melatonin and orlistat combination versus orlistat alone on high fat diet-induced hepatic changes in the adult male albino rats (a histological and morphometric study). Ultrastruct Pathol 2025; 49:20-38. [PMID: 39679624 DOI: 10.1080/01913123.2024.2438380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 11/10/2024] [Accepted: 12/02/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the extremely usual reason of chronic liver disease, extending from simple hepatic steatosis (HS), nonalcoholic steatohepatitis (NASH) to advanced hepatic fibrosis and cirrhosis. Though orlistat is a Food and Drug Administration (FDA) approved drug for long-duration management of obesity, few cases of severe hepatic insult were declared. Melatonin is an efficient antioxidant; it also regulates metabolic processes that lead to fat accumulation and obesity. AIM OF THE WORK The current research aimed to compare the impact of orlistat, melatonin, and their combination on the structural changes of the hepatic tissue of adult male albino rats supplied with high fat diet (HFD). MATERIAL AND METHODS Thirty adult male albino rats divided into five groups. Liver specimens were divided into two parts. One-half was processed to obtain paraffin blocks, and the other half was processed to obtain semithin sections. Morphometric study and statistical analysis were done. RESULTS Hepatic tissue from the HFD group showed steatosis, ballooning, and inflammation and all these parameters were moderately improved - except for inflammation which worsened with therapy. Combined orlistat and melatonin-treated groups showed marked improvement of all parameters as well as marked improvement in the hepatic fibrosis.Orlistat/Melatonin combination therapy is both safe and effective in comparison to orlistat and melatonin monotherapy.
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Affiliation(s)
- Sayed M El-Sayed
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
| | - Gehan A El-Sayed
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
| | - Mansour M A
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
| | - Enas Haridy Ahmed
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
- Faculty of Medicine, Hail University, Hail, Kingdom of Saudi Arabia
| | - Sherif A Kamar
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
- Faculty of Dentistry, Al-Ahliyya Amman University, Amman, Jordan
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Vašura A, Machytka E, Urban O, Macháčková J, Pavliska L, Berka Z, Švagera Z, Bužga M. Effect of bariatric endoscopy on liver fibrosis and steatosis and the course of NAFLD - a prospective interventional study. Ann Hepatol 2024; 30:101765. [PMID: 39674369 DOI: 10.1016/j.aohep.2024.101765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 11/25/2024] [Accepted: 11/27/2024] [Indexed: 12/16/2024]
Abstract
INTRODUCTION AND OBJECTIVES With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. MATERIALS AND METHODS This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. RESULTS Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). CONCLUSIONS Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. CLINICALTRIALS GOV REGISTRATION NCT04895943.
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Affiliation(s)
- Adam Vašura
- Department of Internal Medicine and Cardiology, Division of Gastroenterology, hepatology and pancreatology, University Hospital Ostrava, 17. Listopadu 1740, 70800, Ostrava, Czech Republic; Department of Clinical Studies, Faculty of Medicine, University of Ostrava, Syllabova 19, 70030, Ostrava, Czech Republic.
| | - Evžen Machytka
- Department of Internal Medicine and Cardiology, Division of Gastroenterology, hepatology and pancreatology, University Hospital Ostrava, 17. Listopadu 1740, 70800, Ostrava, Czech Republic.
| | - Ondřej Urban
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, Zdravotníků 248/7, 779 00, Olomouc, Czech Republic.
| | - Jitka Macháčková
- Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Syllabova 19, 70030, Ostrava, Czech Republic.
| | - Lubomír Pavliska
- Research and Education department, University Hospital Ostrava, 17. Listopadu 1740, 70800, Ostrava, Czech Republic.
| | - Zdeněk Berka
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, Zdravotníků 248/7, 779 00, Olomouc, Czech Republic.
| | - Zdeněk Švagera
- Institute of Laboratory Medicine, University Hospital Ostrava,17. Listopadu 1740, 70800, Ostrava, Czech Republic.
| | - Marek Bužga
- Institute of Laboratory Medicine, University Hospital Ostrava,17. Listopadu 1740, 70800, Ostrava, Czech Republic; Department of Physiology and Pathophysiology, Faculty of Medicine, University of Ostrava, Syllabova 19, 70030, Ostrava, Czech Republic.
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4
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Katsarou A, Tsioulos G, Kassi E, Chatzigeorgiou A. Current and experimental pharmacotherapy for the management of non-alcoholic fatty liver disease. Hormones (Athens) 2024; 23:621-636. [PMID: 39112786 DOI: 10.1007/s42000-024-00588-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 07/17/2024] [Indexed: 10/29/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with its incidence increasing in parallel with the global prevalence of obesity and type 2 diabetes mellitus. Despite our steadily increasing knowledge of its pathogenesis, there is as yet no available pharmacotherapy specifically tailored for NAFLD. To define the appropriate management, it is important to clarify the context in which the disease appears. In the case of concurrent metabolic comorbidities, NAFLD patients are treated by targeting these comorbidities, such as diabetes and obesity. Thus, GLP-1 analogs, PPAR, and SGLT2 inhibitors have recently become central to the treatment of NAFLD. In parallel, randomized trials are being conducted to explore new agents targeting known pathways involved in NAFLD progression. However, there is an imperative need to intensify the effort to design new, safe drugs with biopsy-proven efficacy. Of note, the main target of the pharmacotherapy should be directed to the regression of fibrotic NASH, as this histologic stage has been correlated with increased overall as well as liver-related morbidity and mortality. Herein we discuss the drugs currently at the forefront of NAFLD treatment.
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Affiliation(s)
- Angeliki Katsarou
- 251 Hellenic Airforce General Hospital, 1 P.Kanellopoulou Str, Athens, 11525, Greece.
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens, 11527, Greece.
| | - Georgios Tsioulos
- 4th Department of Internal Medicine, Medical School, University General Hospital Attikon, National and Kapodistrian University of Athens, 1 Rimini Str, Athens, 12462, Greece
| | - Eva Kassi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 115 27, Athens, Greece
| | - Antonios Chatzigeorgiou
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens, 11527, Greece
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Pericàs JM, Anstee QM, Augustin S, Bataller R, Berzigotti A, Ciudin A, Francque S, Abraldes JG, Hernández-Gea V, Pons M, Reiberger T, Rowe IA, Rydqvist P, Schabel E, Tacke F, Tsochatzis EA, Genescà J. A roadmap for clinical trials in MASH-related compensated cirrhosis. Nat Rev Gastroenterol Hepatol 2024; 21:809-823. [PMID: 39020089 DOI: 10.1038/s41575-024-00955-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/03/2024] [Indexed: 07/19/2024]
Abstract
Although metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of cirrhosis worldwide, therapeutic options are limited and the number of clinical trials in MASH-related compensated cirrhosis is low as compared to those conducted in earlier disease stages. Moreover, designing clinical trials in MASH cirrhosis presents a series of challenges regarding the understanding and conceptualization of the natural history, regulatory considerations, inclusion criteria, recruitment, end points and trial duration, among others. The first international workshop on the state of the art and future direction of clinical trials in MASH-related compensated cirrhosis was held in April 2023 at Vall d'Hebron University Hospital in Barcelona (Spain) and was attended by a group of international experts on clinical trials from academia, regulatory agencies and industry, encompassing expertise in MASH, cirrhosis, portal hypertension, and regulatory affairs. The presented Roadmap summarizes important content of the workshop on current status, regulatory requirements and end points in MASH-related compensated cirrhosis clinical trials, exploring alternative study designs and highlighting the challenges that should be considered for upcoming studies on MASH cirrhosis.
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Affiliation(s)
- Juan M Pericàs
- Liver Unit, Division of Digestive Diseases, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.
- Centros de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
| | - Quentin M Anstee
- Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Newcastle NIHR Biomedical Research Center, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK
| | | | - Ramón Bataller
- Liver Unit, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat Barcelona, Barcelona, Spain
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Andreea Ciudin
- Endocrinology and Nutrition Department, Morbid Obesity Unit Coordinator, Vall d'Hebron University Hospital, Barcelona, Spain
- Centros de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain
| | - Sven Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, InflaMed Centre of Excellence, Laboratory for Experimental Medicine and Paediatrics, Translational Sciences in Inflammation and Immunology, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium
| | - Juan G Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
| | - Virginia Hernández-Gea
- Centros de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Liver Unit, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat Barcelona, Barcelona, Spain
| | - Mònica Pons
- Liver Unit, Division of Digestive Diseases, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Ian A Rowe
- Leeds Institute for Medical Research, University of Leeds, Leeds, UK
| | - Peter Rydqvist
- Medical Department, Madrigal Pharmaceuticals, West Conshohocken, PA, USA
| | - Elmer Schabel
- Federal Institute for Drugs and Medical Devices, Bonn, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Joan Genescà
- Liver Unit, Division of Digestive Diseases, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centros de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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Gwon HJ, Chung YH, Lim DS, Cho W, Choi SW, Abd El-Aty AM, Song JH, Shin YK, Jeong JH, Jung TW. Uvaol ameliorates lipid deposition in hyperlipidemic hepatocytes by suppressing protein-tyrosine phosphatase 1B/ER stress signaling. Biochem Biophys Res Commun 2024; 730:150387. [PMID: 39002201 DOI: 10.1016/j.bbrc.2024.150387] [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: 07/02/2024] [Revised: 07/02/2024] [Accepted: 07/09/2024] [Indexed: 07/15/2024]
Abstract
Uvaol (UV), a pentacyclic triterpene found in olives and virgin olive oil, is known for its anti-inflammatory and antioxidant effects in various disease models. While olive oil is reported to reduce obesity and insulin resistance, the specific impact of UV on liver lipid metabolism and its molecular mechanisms are not fully understood. In this study, hepatic lipid accumulation was measured using oil red O staining, and protein expression levels in liver cells were assessed via Western blot analysis. Apoptosis was evaluated through cell viability and caspase 3 activity assays. UV treatment reduced lipid accumulation, fatty acid uptake, apoptosis, and ER stress in palmitate-treated liver cells. Additionally, UV enhanced fatty acid oxidation. Mechanistically, increased SIRT6 expression and autophagy were observed in UV-treated cells. SIRT6-targeted siRNA or 3-methyladenine blocked the effects of UV in hyperlipidemic cells. In conclusion, UV improves SIRT6/autophagy signaling, reducing lipid deposition and apoptosis in liver cells under high lipid conditions. This in vitro study provides strong evidence for potential therapeutic strategies for hepatic steatosis.
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Affiliation(s)
- Hyeon Ji Gwon
- Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea
| | - Yoon Hee Chung
- Department of Anatomy, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
| | - Do Su Lim
- Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea
| | - Wonjun Cho
- Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
| | - Sung Woo Choi
- Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
| | - A M Abd El-Aty
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 12211, Giza, Egypt; Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, 25240, Turkey.
| | - Jin-Ho Song
- Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
| | - Yong Kyoo Shin
- Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
| | - Ji Hoon Jeong
- Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea.
| | - Tae Woo Jung
- Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
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Tacke F, Horn P, Wai-Sun Wong V, Ratziu V, Bugianesi E, Francque S, Zelber-Sagi S, Valenti L, Roden M, Schick F, Yki-Järvinen H, Gastaldelli A, Vettor R, Frühbeck G, Dicker D. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 2024; 81:492-542. [PMID: 38851997 DOI: 10.1016/j.jhep.2024.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 04/30/2024] [Indexed: 06/10/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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Raja A, Subhash Sagar R, Saeed S, Zia Ul Haq A, Khan O, Dileep Bhimani P, Raja S, Deepak F, Ahmed M, Ashir Shafique M, Saqlain Mustafa M, Sohaib Asghar M, Sharma V. Safety and efficacy of resmetirom in the treatment of patients with non-alcoholic steatohepatitis and liver fibrosis: a systematic review and meta-analysis. Ann Med Surg (Lond) 2024; 86:4130-4138. [PMID: 38989228 PMCID: PMC11230798 DOI: 10.1097/ms9.0000000000002195] [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: 03/17/2024] [Accepted: 05/08/2024] [Indexed: 07/12/2024] Open
Abstract
Introduction Non-alcoholic fatty liver disease (NAFLD), spanning from non-alcoholic steatohepatitis (NASH) to liver fibrosis, poses a global health challenge amid rising obesity and metabolic syndrome rates. Effective pharmacological treatments for NASH and liver fibrosis are limited. Objective This study systematically reviews and meta-analyzes the safety and efficacy of resmetirom, a selective thyroid hormone receptor-β agonist, in NASH and liver fibrosis treatment. By analyzing data from clinical trials, we aim to offer evidence-based recommendations for resmetirom's use in managing these conditions and identify avenues for future research. Methods Electronic databases (PubMed, Scopus, Science Direct, Google Scholar, ClinicalTrials.gov, and Cochrane CENTRAL) were systematically searched, supplemented by manual screening of relevant sources. Only English-language randomized controlled trials were included. Data extraction, risk of bias assessment, pooled analyses, and meta-regression were performed. Results Three randomized controlled trials involving 2231 participants were analyzed. Resmetirom demonstrated significant reductions in hepatic fat fraction [standardized mean difference (SMD) -4.61, 95% CI -6.77 to -2.44, P < 0.0001], NASH resolution without worsening fibrosis [risk ratio (RR) 2.51, 95% CI 1.74-3.64, P = 0.00001), and liver fibrosis improvement (RR 2.31, 95% CI 1.20-4.44, P = 0.01). Secondary outcomes showed significant improvements in lipid profiles, liver enzymes, and NASH biomarkers with resmetirom treatment. Meta-regression revealed associations between covariates and primary outcomes. Conclusion Resmetirom exhibits promising efficacy in reducing hepatic fat, improving NASH resolution, and ameliorating liver fibrosis with a favorable safety profile. Further research is warranted to validate findings and optimize therapeutic strategies for NASH and liver fibrosis management.
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Affiliation(s)
- Adarsh Raja
- Department of Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari
| | - Raja Subhash Sagar
- Department of Internal Medicine, Liaquat University of Medical & Health Science, Jamshoro
| | - Sadia Saeed
- Department of Internal Medicine, Women Medical College Abbotabad, Abbottabad, Pakistan
| | - Amna Zia Ul Haq
- Department of Internal Medicine, Dow University of Health Sciences
| | - Owais Khan
- Department of Internal Medicine, Dow University of Health Sciences
| | | | - Sandesh Raja
- Department of Internal Medicine, Dow University of Health Sciences
| | - Fnu Deepak
- Department of Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari
| | - Muhammad Ahmed
- Department of Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari
| | | | | | - Muhammad Sohaib Asghar
- Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Varsha Sharma
- Department of Internal Medicine, Nepal Medical College, Gokarneshwar, Nepal
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EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Obes Facts 2024; 17:374-444. [PMID: 38852583 PMCID: PMC11299976 DOI: 10.1159/000539371] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 05/15/2024] [Indexed: 06/11/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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Wang H, Ma Q, Chen Y, Luo L, Ye J, Zhong B. Optimized strategy among diet, exercise, and pharmacological interventions for nonalcoholic fatty liver disease: A network meta-analysis of randomized controlled trials. Obes Rev 2024; 25:e13727. [PMID: 38509775 DOI: 10.1111/obr.13727] [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: 03/16/2023] [Revised: 01/23/2024] [Accepted: 01/30/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND Emerging treatment methods, including exercise, diet, and drugs, for nonalcoholic fatty liver disease have been proposed. However, the differences in their efficacy have not been determined. We aimed to compare the effects of these treatments excluding surgery via a systematic review and network meta-analysis of randomized controlled trials. DATA SOURCE The data sources included PubMed, Embase, Web of Science and Cochrane up to February 1st, 2023. The endpoints consisted of body mass index (BMI), serum markers of metabolism and liver injury markers, liver fat content, and stiffness. RESULTS A total of 174 studies with 10,183 patients were included in this meta-analysis. In terms of improving BMI, Pan-agonist of peroxisome proliferator-activated receptors (PPAR) is the best treatment with the highest SUCRA (surface under the cumulative ranking) of 84.8% (mean = -3.40, 95% CI -5.55, -1.24) by the comparative effectiveness ranking. GLP-1 (glucagon-like peptide-1) has the best effect in improving the liver fat content based on the MRI-PDFF, steatosis score (SUCRA 99.7%, mean = -2.19, 95% CI -2.90, -1.48) and ballooning score (SUCRA 61.2%, mean = -0.82, 95% CI -4.46, 2.83). CONCLUSIONS Pan-agonist of PPAR was the most efficacious regimen in lowering BMIs, whereas GLP-1R agonists achieved the highest efficacy of steatosis improvement in this network meta-analysis.
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Affiliation(s)
- Hao Wang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Qianqian Ma
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Infectious Diseases, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Youpeng Chen
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Ling Luo
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junzhao Ye
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bihui Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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11
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Mahmoud A, Mohamed I, Abuelazm M, Ahmed AAS, Saeed A, Elshinawy M, Almaadawy O, Abdelazeem B. Efficacy of orlistat in obese patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials. Proc AMIA Symp 2024; 37:603-612. [PMID: 38910819 PMCID: PMC11188793 DOI: 10.1080/08998280.2024.2335829] [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: 11/09/2023] [Accepted: 03/18/2024] [Indexed: 06/25/2024] Open
Abstract
Objective: Nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant contributor to chronic liver disease worldwide. Orlistat blocks intestinal fat absorption, leading to decreased liver fat content. Therefore, it is a viable option for NAFLD management. Methods: We performed a systematic review and metaanalysis using randomized controlled trials (RCTs). We used mean difference (MD) to pool continuous outcomes presented with the corresponding confidence interval (CI). Results: We included four RCTs with a total of 379 patients. Orlistat was effective in reducing liver fat content (MD: -5.02, 95% CI [-7.23, -2.82], P = 0.00001), alanine transferase (MD: -10.03, 95% CI [-17.80, -2.26], P = 0.01), aspartate transferase (MD: -4.29, 95% CI [-7.59, -0.99], P = 0.01), waist circumference (MD: -3.18, 95% CI [-4.25, -2.10], P = 0.00001), body mass index (MD: -1.03, 95% CI [-1.34, -0.73], P = 0.00001), total cholesterol (MD: -3.75, 95% CI [-4.02, -3.49], P = 0.00001), and low-density lipoprotein (MD: -3.83, 95% CI [-4.05, -3.61], P = 0.00001). However, orlistat was associated with increased serum triglycerides (MD: 7.46, 95% CI [6.48, 8.44], P = 0. 00001). Conclusion: Orlistat is a viable option for NAFLD management; however, it increases triglyceride levels. Larger RCTs are required.
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Affiliation(s)
| | - Islam Mohamed
- Department of Internal Medicine, University of Missouri, Kansas City, Missouri, USA
| | | | | | | | | | - Omar Almaadawy
- Department of Internal Medicine, MedStar Health, Baltimore, Maryland, USA
| | - Basel Abdelazeem
- Cardiology Department, West Virginia University, Morgantown, West Virginia, USA
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12
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Zahmatkesh A, Sohouli MH, Shojaie S, Rohani P. The effect of orlistat in the treatment of non-alcoholic fatty liver in adolescents with overweight and obese. Eur J Pediatr 2024; 183:1173-1182. [PMID: 38081992 DOI: 10.1007/s00431-023-05369-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 12/01/2023] [Accepted: 12/04/2023] [Indexed: 03/20/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD), which can manifest as nonalcoholic steatohepatitis (NASH) or severe fibrosis, is the most prevalent chronic liver disease in children and adolescents. However, there is no proven cure for it so far. This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. This study is a randomized controlled trial (RCT). Fifty-three adolescents with overweight/obese as well as with NAFLD randomly allocated to receive orlistat (n = 27) or placebo as control (n = 26) for 12 weeks. In addition, NAFLD activity score, anthropometric factors, biochemical parameters including serum levels of lipid profiles, liver enzyme, and glucose metabolism taken from subjects at baseline and end of the study were investigated. The findings of our article indicated that orlistat improves liver enzymes (alanine transaminase and aspartate transaminase) (P = < 0.001), steatosis score (P = 0.001), NAFLD activity score (P = < 0.001), weight (P = < 0.001), body mass index (BMI) (P = < 0.001), waist circumferences (WC) (P = < 0.001), BMI-Z score (P = < 0.001), glucose metabolism (P = 0.001), total cholesterol (TC) (P = 0.009), low density lipoprotein-cholesterol (LDL) (P = < 0.001), and high density lipoprotein-cholesterol HDL levels (P = 0.014) compared to the control group after adjusting for possible confounders for 12 weeks. However, no significant changes were observed on triglyceride (TG) following intake of orlistat compared to placebo after adjusting for confounders. CONCLUSION The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks. TRIAL REGISTRATION (Clinical trial registry number: IRCT20220409054467N2, with a registration date of 2022-05-13). WHAT IS KNOWN • Among the interventions of interest for the management of pediatric NAFLD, we can mention lifestyle and pharmaceutical measures. WHAT IS NEW • This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. • The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks.
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Affiliation(s)
- Arefeh Zahmatkesh
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hassan Sohouli
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Shima Shojaie
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Pejman Rohani
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
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13
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Genua I, Cusi K. Pharmacological Approaches to Nonalcoholic Fatty Liver Disease: Current and Future Therapies. Diabetes Spectr 2024; 37:48-58. [PMID: 38385098 PMCID: PMC10877217 DOI: 10.2337/dsi23-0012] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/23/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), can promote the development of cirrhosis, hepatocellular carcinoma, cardiovascular disease, and type 2 diabetes. Similarly, type 2 diabetes confers the greatest risk for the development of NASH, especially when associated with obesity. Although lifestyle changes are critical to success, early implementation of pharmacological treatments for obesity and type 2 diabetes are essential to treat NASH and avoid disease progression. This article reviews current guidance regarding the use of pharmacological agents such as pioglitazone, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors in the setting of NAFLD and NASH. It also reviews the latest information on new drugs currently being investigated for the treatment of NASH.
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Affiliation(s)
- Idoia Genua
- IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
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14
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Godoy-Matos AF, Valério CM, Silva Júnior WS, de Araujo-Neto JM, Bertoluci MC. 2024 UPDATE: the Brazilian Diabetes Society position on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) in people with prediabetes or type 2 diabetes. Diabetol Metab Syndr 2024; 16:23. [PMID: 38238868 PMCID: PMC10797995 DOI: 10.1186/s13098-024-01259-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 01/04/2024] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease affecting 30% of the world's population and is often associated with metabolic disorders such as metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease. This review is an update of the Brazilian Diabetes Society (Sociedade Brasileira de Diabetes [SBD]) evidence-based guideline for the management of MASLD in clinical practice. METHODS The methodology was published previously and was defined by the internal institutional steering committee. The SBD Metabolic Syndrome and Prediabetes Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed with the MeSH terms [diabetes] and [fatty liver]. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to MASLD. RESULTS AND CONCLUSIONS The SBD Metabolic Syndrome and Prediabetes Department formulated 9 recommendations for the management of MASLD in people with prediabetes or T2D. Screening for the risk of advanced fibrosis associated with MASLD is recommended in all adults with prediabetes or T2D. Lifestyle modification (LSM) focusing on a reduction in body weight of at least 5% is recommended as the first choice for these patients. In situations where LSMs are insufficient to achieve weight loss, the use of anti-obesity medications is recommended for those with a body mass index (BMI) ≥ 27 kg/m2. Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) monotherapy are the first-line pharmacological treatments for steatohepatitis in people with T2D, and sodium-glucose cotransporter-2 (SGLT2) inhibitors may be considered in this context. The combination of these agents may be considered in the treatment of steatohepatitis and/or fibrosis, and bariatric surgery should be considered in patients with a BMI ≥ 35 kg/m2, in which the combination of LSM and pharmacotherapy has not been shown to be effective in improving MASLD.
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Affiliation(s)
- Amélio F Godoy-Matos
- Sociedade Brasileira de Diabetes (SBD), São Paulo, Brazil
- Instituto Estadual de Diabetes e Endocrinologia do Rio de Janeiro (IEDE), Rio de Janeiro, RJ, Brazil
| | - Cynthia Melissa Valério
- Sociedade Brasileira de Diabetes (SBD), São Paulo, Brazil
- Instituto Estadual de Diabetes e Endocrinologia do Rio de Janeiro (IEDE), Rio de Janeiro, RJ, Brazil
| | - Wellington S Silva Júnior
- Sociedade Brasileira de Diabetes (SBD), São Paulo, Brazil.
- Endocrinology Discipline, Department of Medicine I, Faculty of Medicine, Center of Biological Sciences, Universidade Federal do Maranhão (UFMA), Praça Gonçalves Dias, 21, Centro, São Luís, MA, CEP 65020-240, Brazil.
| | - João Marcello de Araujo-Neto
- Sociedade Brasileira de Diabetes (SBD), São Paulo, Brazil
- Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Marcello Casaccia Bertoluci
- Sociedade Brasileira de Diabetes (SBD), São Paulo, Brazil
- Universidade Federal do Rio Grande Do Sul (UFRGS), Porto Alegre, RS, Brazil
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15
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Bril F. Nonalcoholic fatty liver disease: What comes before and what are the consequences? CHRONIC COMPLICATIONS OF DIABETES MELLITUS 2024:185-206. [DOI: 10.1016/b978-0-323-88426-6.00017-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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16
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Medina SP, Kim RG, Magee C, Stapper N, Khalili M. Cross-sectional study on stigma and motivation to adhere to lifestyle modification among vulnerable populations with fatty liver disease. Obes Sci Pract 2023; 9:581-589. [PMID: 38090690 PMCID: PMC10712403 DOI: 10.1002/osp4.688] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 05/16/2023] [Accepted: 05/18/2023] [Indexed: 10/16/2024] Open
Abstract
Objectives Adherence to lifestyle modification (diet, exercise, and alcohol cessation) for fatty liver disease (FLD) management remains challenging. The study examined stigma, barriers, and factors associated with motivation to adhere to lifestyle modification in a diverse and vulnerable population with FLD. Methods From 2/19/2020 to 2/28/2022, 249 FLD patients within San Francisco safety-net hepatology clinics were surveyed along with clinical data taken from medical records. Multivariable modeling assessed factors associated with motivation to adhere to lifestyle modification in a cross-sectional study. Results Median age was 53 years, 59% female, 59% Hispanic, 25% Asian/Pacific Islander, 9% White, and 2% Black, 79% were non-English speakers, 64% had ≤ high school education, and 82% reported <$30,000 annual income. Common comorbidities included hyperlipidemia (47%), hypertension (42%), diabetes (39%), and heavy alcohol use (22%). Majority (78%) reported experiencing stigma, 41% reported extreme motivation, and 58% reported ≥ two barriers. When controlling for age, sex, Hispanic ethnicity, alcohol consumption, BMI, >high school (coef 1.41, 95% CI 0.34-2.48), stigma (coef 0.34, 95% CI 0.07-0.62), and depression (coef -1.52, 95% CI -2.79 to -0.26) were associated with motivation. Conclusions Stigma is commonly reported among FLD patients. Interventions to enhance patient education and mental health support are critical to FLD management, especially in vulnerable populations.
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Affiliation(s)
- Sheyla P. Medina
- Department of MedicineDivision of Gastroenterology and HepatologyUniversity of CaliforniaSan FranciscoCaliforniaUSA
| | - Rebecca G. Kim
- Department of MedicineDivision of Gastroenterology and HepatologyUniversity of CaliforniaSan FranciscoCaliforniaUSA
| | - Catherine Magee
- Division of Gastroenterology and HepatologyZuckerberg San Francisco GeneralSan FranciscoCaliforniaUSA
| | - Noah Stapper
- Division of Gastroenterology and HepatologyZuckerberg San Francisco GeneralSan FranciscoCaliforniaUSA
| | - Mandana Khalili
- Department of MedicineDivision of Gastroenterology and HepatologyUniversity of CaliforniaSan FranciscoCaliforniaUSA
- Division of Gastroenterology and HepatologyZuckerberg San Francisco GeneralSan FranciscoCaliforniaUSA
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17
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Gowda D, Shekhar C, B. Gowda SG, Chen Y, Hui SP. Crosstalk between Lipids and Non-Alcoholic Fatty Liver Disease. LIVERS 2023; 3:687-708. [DOI: 10.3390/livers3040045] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), a complex liver disorder that can result in non-alcoholic steatohepatitis, cirrhosis, and liver cancer, is the accumulation of fat in the liver seen in people due to metabolic dysfunction. The pathophysiology of NAFLD is influenced by several variables, such as metabolic dysregulation, oxidative stress, inflammation, and genetic susceptibility. This illness seriously threatens global health because of its link to obesity, insulin resistance, type 2 diabetes, and other metabolic disorders. In recent years, lipid–NAFLD crosstalk has drawn a lot of interest. Through numerous methods, lipids have been connected to the onset and advancement of the illness. The connection between lipids and NAFLD is the main topic of the current review, along with the various therapeutic targets and currently available drugs. The importance of hepatic lipid metabolism in the progression of NAFLD is summarized with the latest results in the field.
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Affiliation(s)
- Divyavani Gowda
- Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan
| | - Chandra Shekhar
- Department of Physiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Siddabasave Gowda B. Gowda
- Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan
- Graduate School of Global Food Resources, Hokkaido University, Sapporo 060-0812, Japan
| | - Yifan Chen
- Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan
| | - Shu-Ping Hui
- Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan
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18
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Beiriger J, Chauhan K, Khan A, Shahzad T, Parra NS, Zhang P, Chen S, Nguyen A, Yan B, Bruckbauer J, Halegoua-DeMarzio D. Advancements in Understanding and Treating NAFLD: A Comprehensive Review of Metabolic-Associated Fatty Liver Disease and Emerging Therapies. LIVERS 2023; 3:637-656. [DOI: 10.3390/livers3040042] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and NASH, emphasizing their multifactorial nature. The manuscript identifies various contributors to NAFLD development, including genetic, dietary, and environmental factors, while examining the intricate interplay between these factors and their impact on hepatic lipid metabolism, inflammation, and insulin resistance. Genetic predisposition, dietary fat intake, and excessive fructose consumption are discussed as significant contributors to NAFLD progression. The article emphasizes the lack of a single therapeutic approach and underscores the need for combination strategies. Lifestyle interventions, particularly weight loss through diet and exercise, remain crucial, while pharmacological options like GLP-1 receptor agonists, obeticholic acid, lanifibranor, and resmetirom show promise but require further validation. Bariatric surgery and emerging endoscopic procedures offer potential in eligible patients. In sum, this article underscores the complexity of NAFLD and NASH, addresses key factors influencing pathogenesis, and discusses emerging therapies advocating for a multifaceted approach to this increasingly prevalent and clinically relevant condition.
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Affiliation(s)
- Jacob Beiriger
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Kashyap Chauhan
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Adnan Khan
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Taha Shahzad
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Natalia Salinas Parra
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Peter Zhang
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Sarah Chen
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Anh Nguyen
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Brian Yan
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - John Bruckbauer
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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Bhopale KK, Srinivasan MP. Therapeutics for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD). LIVERS 2023; 3:597-617. [DOI: 10.3390/livers3040040] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Metabolic dysfunction associated fatty liver disease (MAFLD) has been recently recognized as a new global chronic liver disease entity with non-alcoholic fatty liver disease (NAFLD) associated with overweight/obesity or type 2 diabetes mellitus (T2DM) and evidence of metabolic dysregulation. Due to the rising rates of obesity and diabetes, MAFLD is considered a rapidly emerging chronic liver disease globally. Nearly 25–30% of the global population poses health issues due to MAFLD with a substantial economic burden to societies. Disease progression depends on the persistence of risk factors and etiological agents, from simple steatosis, hepatitis, fibrosis, to cirrhosis, and if untreated, leads to hepatocellular carcinoma. In this review article we summarize various risk and etiological factors, diagnostic techniques, and therapeutic evaluation of pharmacological agents developed for MAFLD. Effective pharmaceutical agents for the treatment of MAFLD (and NAFLD) are lacking, and research is ongoing to search for effective medications in this direction. Currently, pioglitazone is advised for MAFLD patients, whereas Vitamin E is advised for non-diabetic MAFLD patients with ≥F2 non-cirrhosis. Current approaches to disease management emphasize diet control, lifestyle changes, and weight loss. In this review, we summarized the pharmacological agents currently being developed and their current status to treat patients with MAFLD.
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Affiliation(s)
- Kamlesh K. Bhopale
- Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Mukund P. Srinivasan
- Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA
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20
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Ding Y, Deng Q, Yang M, Niu H, Wang Z, Xia S. Clinical Classification of Obesity and Implications for Metabolic Dysfunction-Associated Fatty Liver Disease and Treatment. Diabetes Metab Syndr Obes 2023; 16:3303-3329. [PMID: 37905232 PMCID: PMC10613411 DOI: 10.2147/dmso.s431251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 10/10/2023] [Indexed: 11/02/2023] Open
Abstract
Obesity,and metabolic dysfunction-associated fatty liver disease (MAFLD) have reached epidemic proportions globally. Obesity and MAFLD frequently coexist and act synergistically to increase the risk of adverse clinical outcomes (both hepatic and extrahepatic). Type 2 diabetes mellitus (T2DM) is the most important risk factor for rapid progression of steatohepatitis and advanced fibrosis. Conversely, the later stages of MAFLD are associated with an increased risk of T2DM incident. According to the proposed criteria, MAFLD is diagnosed in patients with liver steatosis and in at least one in three: overweight or obese, T2DM, or signs of metabolic dysregulation if they are of normal weight. However, the clinical classification and correlation between obesity and MAFLD is more complex than expected. In addition, treatment for obesity and MAFLD are associated with a reduced risk of T2DM, suggesting that liver-based treatments could reduce the risk of developing T2DM. This review describes the clinical classification of obesity and MAFLD, discusses the clinical features of various types of obesity and MAFLD, emphasizes the role of visceral obesity and insulin resistance (IR) in the development of MAFLD,and summarizes the existing treatments for obesity and MAFLD that reduce the risk of developing T2DM.
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Affiliation(s)
- Yuping Ding
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Quanjun Deng
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Mei Yang
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Haiyan Niu
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Zuoyu Wang
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Shihai Xia
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
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Stine JG, Long MT, Corey KE, Sallis RE, Allen AM, Armstrong MJ, Conroy DE, Cuthbertson DJ, Duarte-Rojo A, Hallsworth K, Hickman IJ, Kappus MR, Keating SE, Pugh CJA, Rotman Y, Simon TL, Vilar-Gomez E, Wai-Sun Wong V, Schmitz KH. Physical Activity and Nonalcoholic Fatty Liver Disease: A Roundtable Statement from the American College of Sports Medicine. Med Sci Sports Exerc 2023; 55:1717-1726. [PMID: 37126039 PMCID: PMC10524517 DOI: 10.1249/mss.0000000000003199] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
ABSTRACT Although physical activity (PA) is crucial in the prevention and clinical management of nonalcoholic fatty liver disease, most individuals with this chronic disease are inactive and do not achieve recommended amounts of PA. There is a robust and consistent body of evidence highlighting the benefit of participating in regular PA, including a reduction in liver fat and improvement in body composition, cardiorespiratory fitness, vascular biology, and health-related quality of life. Importantly, the benefits of regular PA can be seen without clinically significant weight loss. At least 150 min of moderate or 75 min of vigorous intensity PA are recommended weekly for all patients with nonalcoholic fatty liver disease, including those with compensated cirrhosis. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. In this roundtable document, the benefits of PA are discussed, along with recommendations for 1) PA assessment and screening; 2) how best to advise, counsel, and prescribe regular PA; and 3) when to refer to an exercise specialist.
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Affiliation(s)
- Jonathan G. Stine
- Division of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University- Milton S. Hershey Medical Center, Hershey PA
- Department of Public Health Sciences, The Pennsylvania State University- College of Medicine, Hershey PA
| | - Michelle T. Long
- Section of Gastroenterology, Evans Department of Medicine, Boston University School of Medicine, Boston, MA
| | - Kathleen E. Corey
- Division of Gastroenterology and Hepatology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Robert E. Sallis
- Department of Family Medicine and Sports Medicine, Kaiser Permanente Medical Center, Fontana, CA
| | - Alina M. Allen
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN
| | - Matthew J. Armstrong
- Liver Transplant Unit, Queen Elizabeth University Hospitals Birmingham, and NIHR Birmingham Biomedical Research Centre, Birmingham, UNITED KINGDOM
| | - David E. Conroy
- Department of Kinesiology, The Pennsylvania State University, University Park, PA
| | - Daniel J. Cuthbertson
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UNITED KINGDOM
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, IL
| | - Kate Hallsworth
- Newcastle NIHR Biomedical Research Centre and the Liver Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UNITED KINGDOM
| | - Ingrid J. Hickman
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Queensland, AUSTRALIA
| | - Matthew R. Kappus
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC
| | - Shelley E. Keating
- School of Human Movement and Nutrition Sciences, The University of Queensland, St Lucia, Queensland, AUSTRALIA
| | - Christopher J. A. Pugh
- Cardiff School of Sport & Health Sciences, Cardiff Metropolitan University, Cardiff, UNITED KINGDOM
| | - Yaron Rotman
- Liver & Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| | - Tracey L. Simon
- Division of Gastroenterology and Hepatology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology. Indiana University School of Medicine. Indianapolis
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, CHINA
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Agyapong G, Dashti F, Banini BA. Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies. Ann N Y Acad Sci 2023; 1526:16-29. [PMID: 37400359 PMCID: PMC10524684 DOI: 10.1111/nyas.15012] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/05/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease worldwide and a leading indication for liver transplantation in the United States. NAFLD encompasses a heterogeneous clinicopathologic spectrum, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis, and progressive fibrosis, which can lead to end-stage liver disease including cirrhosis and hepatocellular cancer. Predictive models suggest that over 100 million adults in the United States will have NAFLD by 2030, representing over a third of the population. In this manuscript, we provide an overview of NAFLD risk factors, natural history (including hepatic and extra-hepatic outcomes), diagnosis, and current management strategies.
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Affiliation(s)
- George Agyapong
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut, USA
- Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Farzaneh Dashti
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Bubu A Banini
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut, USA
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Bril F, Sanyal A, Cusi K. Metabolic Syndrome and Its Association with Nonalcoholic Steatohepatitis. Clin Liver Dis 2023; 27:187-210. [PMID: 37024202 DOI: 10.1016/j.cld.2023.01.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
The relationship between insulin resistance, metabolic syndrome (MetS), and nonalcoholic fatty liver disease (NAFLD) is complicated. Although insulin resistance is almost universal in people with NAFLD and MetS, NAFLD may be present without features of MetS and vice versa. While NAFLD has a strong correlation with cardiometabolic risk factors, these are not intrinsic components of this condition. Taken together, our knowledge gaps call for caution regarding the common assertion that NAFLD is the hepatic manifestation of the MetS, and for defining NAFLD in broad terms as a "metabolic dysfunction" based on a diverse and poorly understood constellation of cardiometabolic features.
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Affiliation(s)
- Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Arun Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine Internal Medicine, Virginia Commonwealth University
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
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Camacho RC, Polidori D, Chen T, Chen B, Hsu HH, Gao B, Marella M, Lubomirski M, Beavers T, Cabrera J, Wong P, Nawrocki AR. Validation of a diet-induced Macaca fascicularis model of non-alcoholic steatohepatitis with dietary and pioglitazone interventions. Diabetes Obes Metab 2023; 25:1068-1079. [PMID: 36546607 DOI: 10.1111/dom.14955] [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: 06/07/2022] [Revised: 11/28/2022] [Accepted: 12/08/2022] [Indexed: 12/24/2022]
Abstract
AIM To develop an obese, insulin-resistant cynomolgus monkey model of non-alcoholic steatohepatitis (NASH) with fibrosis with a high fat/high cholesterol (HFHC) diet (with or without high fructose) and test its responsiveness to caloric restriction or pioglitazone. METHODS First, two groups of monkeys (n = 24/group) with histologically proven NASH and fibrosis were fed the HFHC diet for 17 weeks. The treatment group was subjected to a 40% caloric restriction (CR) and had their diet switched from the HFHC diet to a chow diet (DSCR). Paired liver biopsies were taken before and 17 weeks after DSCR. Subsets of monkeys (nine/group) had whole liver fat content assessed by MRI. Next, two groups of monkeys with histologically proven NASH and fibrosis were treated with vehicle (n = 9) or pioglitazone (n = 20) over 24 weeks. RESULTS The HFHC and DSCR groups lost 0.9% and 11.4% of body weight, respectively. After 17 weeks, non-alcoholic fatty liver disease activity score (NAS) improvement was observed in 66.7% of the DSCR group versus 12.5% of the HFHC group (P < .001). Hepatic fat was reduced to 5.2% in the DSCR group versus 23.0% in the HFHC group (P = .0001). After 24 weeks, NAS improvement was seen in 30% of the pioglitazone group versus 0% of the vehicle group (P = .08). CONCLUSIONS Both weight loss induced by DSCR and treatment with pioglitazone improve the histological features of NASH in a diet-induced cynomolgus monkey model. This model provides a translational preclinical model for testing novel NASH therapies.
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Affiliation(s)
- Raul C Camacho
- Cardiovascular Metabolism, Spring House, Pennsylvania, USA
| | - David Polidori
- Cardiovascular Metabolism, Spring House, Pennsylvania, USA
| | - Tao Chen
- Preclincial Sciences and Translational Safety, Shanghai, China
| | - Bin Chen
- Preclincial Sciences and Translational Safety, Shanghai, China
| | - Helen Han Hsu
- Preclincial Sciences and Translational Safety, Shanghai, China
| | - Bin Gao
- Translational Medicine and Early Development Statistics, Spring House, Pennsylvania, USA
| | | | - Mariusz Lubomirski
- Translational Medicine and Early Development Statistics, Spring House, Pennsylvania, USA
| | - Traymon Beavers
- Translational Medicine and Early Development Statistics, Spring House, Pennsylvania, USA
| | - Javier Cabrera
- Translational Medicine and Early Development Statistics, Spring House, Pennsylvania, USA
| | - Peggy Wong
- Quantitative Sciences, Janssen R&D, Raritan, New Jersey, USA
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Grzych G, Bernard L, Lestrelin R, Tailleux A, Staels B. [State of the art on the pathophysiology, diagnosis and treatment of non-alcoholic steatohepatitis (NASH)]. ANNALES PHARMACEUTIQUES FRANÇAISES 2023; 81:183-201. [PMID: 36126753 DOI: 10.1016/j.pharma.2022.09.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/13/2022] [Indexed: 11/15/2022]
Abstract
NAFLD or non-alcoholic fatty liver disease is one of the complications of obesity and diabetes, the prevalence of which is increasing. The causes of the pathology and its development towards its severe form, NASH or non-alcoholic steatohepatitis, are multiple and still poorly understood. Many different pharmacological classes are being tested in clinical trials to treat NASH, but no pharmaceutical treatment is currently on the market. Moreover, the diagnosis of certainty is only possible by liver biopsy and histological analysis, an invasive procedure with high risk for the patient. It is therefore necessary to better understand the natural history of the disease in order to identify therapeutic targets, but also to identify markers for the diagnosis and monitoring of the disease using a blood sample, which will allow an improvement in patient management.
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Affiliation(s)
- G Grzych
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France.
| | - L Bernard
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - R Lestrelin
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - A Tailleux
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - B Staels
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
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26
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Shi YW, Fan JG. Metabolic-associated fatty liver disease: pharmacological management. COMPREHENSIVE GUIDE TO HEPATITIS ADVANCES 2023:319-341. [DOI: 10.1016/b978-0-323-98368-6.00010-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Liu T, Wu F, Chen K, Pan B, Yin X, You Y, Song Z, Li D, Huang D. Sweet potato extract alleviates high-fat-diet-induced obesity in C57BL/6J mice, but not by inhibiting pancreatic lipases. Front Nutr 2022; 9:1016020. [PMID: 36505243 PMCID: PMC9731405 DOI: 10.3389/fnut.2022.1016020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 11/11/2022] [Indexed: 11/25/2022] Open
Abstract
Scope and aim Sweet potato is widely consumed as a healthy and nutritive vegetable containing bioactive constituents for health promotion. This study investigated the beneficial impact of white-fleshed sweet potato extract (SPE) on high fat diet (HFD)-induced obese mice. Methods and results First, SPE, in which resin glycoside was found as the dominant constituent, was suggested as a potential anti-obesity agent, because 20-70% pancreatic lipase (PL) inhibition was measured with SPE by in vitro turbidity assay and pNPP assay. Hence, next, the effect of SPE on obese mice was detected by oral administration of HFD supplemented with 6% SPE on C57BL/6J mice for 9 weeks. Surprisingly, being the opposite of what was typically observed from a lipase inhibitor such as orlistat, the fecal fat content in SPE-fed obese mice was decreased (p < 0.01). Meanwhile, 6% SPE supplement indeed significantly ameliorated HFD-induced obesity in mice, including body weight gain, fat accumulation, adipocyte enlargement, insulin resistance, and hepatic steatosis (p < 0.05). The improved liver steatosis was found associated with a down-regulating action of SPE on nuclear factor kappa B activation in HFD-fed mice. The anti-obesity influence of SPE was also confirmed on the HepG2 cell model for non-alcoholic fatty liver disease (NAFLD). Conclusion These results indicate that SPE, as a dietary supplement, has the great potential for weight control and treating hepatic steatosis, possibly through a different action mechanism from that of orlistat.
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Affiliation(s)
- Tiange Liu
- National University of Singapore (Suzhou) Research Institute, Suzhou, China
| | - Fan Wu
- National University of Singapore (Suzhou) Research Institute, Suzhou, China
| | - Kejing Chen
- National University of Singapore (Suzhou) Research Institute, Suzhou, China
| | - Bingna Pan
- National University of Singapore (Suzhou) Research Institute, Suzhou, China
| | - Xifeng Yin
- Suzhou Kosmode Biotechnology Company, Suzhou, China
| | - Yilin You
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Zhixuan Song
- Department of Food Science and Technology, National University of Singapore, Singapore, Singapore
| | - Dan Li
- National University of Singapore (Suzhou) Research Institute, Suzhou, China
- Department of Food Science and Technology, National University of Singapore, Singapore, Singapore
| | - Dejian Huang
- National University of Singapore (Suzhou) Research Institute, Suzhou, China
- Department of Food Science and Technology, National University of Singapore, Singapore, Singapore
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Tsankof A, Neokosmidis G, Koureta E, Veneti S, Cholongitas E, Tziomalos K. Which is the optimal antiobesity agent for patients with nonalcoholic fatty liver disease? Front Endocrinol (Lausanne) 2022; 13:984041. [PMID: 36120448 PMCID: PMC9478023 DOI: 10.3389/fendo.2022.984041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 08/12/2022] [Indexed: 11/16/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and affects a considerable proportion of the general population worldwide. Obesity is a major risk factor for development and progression of NAFLD and weight loss is an effective intervention for the management of NAFLD. However, few patients achieve substantial and sustained weight loss with lifestyle measures. Therefore, antiobesity agents are frequently considered in patients with NAFLD but there are limited data on their safety and efficacy. In the present review, we discuss the role of antiobesity agents in the management of NAFLD. All approved antiobesity agents appear to reduce transaminase levels and to improve steatosis in patients with NAFLD. However, their effects on fibrosis are less well studied and whether they affect liver-related outcomes, including progression to cirrhosis and hepatocellular cancer, is unknown. The glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, appear to represent a first-line option in obese patients with NAFLD and type 2 diabetes mellitus (T2DM) since they induce considerable weight loss and have been extensively studied in patients with T2DM. However, more studies are needed to evaluated their effects on liver-related and cardiovascular outcomes in patients with NAFLD, particularly in those without T2DM.
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Affiliation(s)
- Alexandra Tsankof
- First Propedeutic Department of Internal Medicine, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Georgios Neokosmidis
- First Propedeutic Department of Internal Medicine, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Evgenia Koureta
- Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Stavroula Veneti
- First Propedeutic Department of Internal Medicine, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Evangelos Cholongitas
- Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Konstantinos Tziomalos
- First Propedeutic Department of Internal Medicine, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – April 2022 – AWMF-Registernummer: 021–025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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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: 15] [Impact Index Per Article: 5.0] [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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Polyzos SA, Goulis DG, Giouleme O, Germanidis GS, Goulas A. Anti-obesity Medications for the Management of Nonalcoholic Fatty Liver Disease. Curr Obes Rep 2022; 11:166-179. [PMID: 35501557 DOI: 10.1007/s13679-022-00474-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/11/2022] [Indexed: 02/08/2023]
Abstract
PURPOSE OF REVIEW Obesity is closely associated with nonalcoholic fatty liver disease (NAFLD), a highly prevalent disease without any approved medication. The aim of this review was to summarize the evidence on the effect of anti-obesity medications on NAFLD, especially focusing on hepatic histology. RECENT FINDINGS Orlistat and some glucagon-like peptide-1 receptor analogs, including liraglutide and semaglutide, have beneficial effects on hepatic steatosis and inflammation, but not fibrosis. Other anti-obesity medications, including lorcaserin, setmelanotide, phentermine hydrochloric, phentermine/topiramate, and naltrexone/bupropion, have been minimally investigated in NAFLD. Furthermore, medications like sodium-glucose cotransporter-2 inhibitors and farnesoid X receptor have shown beneficial effects in both NAFLD and obesity, but they have not been licensed for either disease. Liraglutide, semaglutide, and orlistat may be currently used in selected patients with obesity and NAFLD. Further research is warranted, since targeting obesity may provide additional benefits on its comorbidities, including NAFLD.
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Affiliation(s)
- Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Campus of Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
| | - Dimitrios G Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Olga Giouleme
- 2nd Propedeutic Department of Internal Medicine, Hippocration Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Georgios S Germanidis
- 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Antonis Goulas
- First Laboratory of Pharmacology, School of Medicine, Campus of Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece
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Xu X, Poulsen KL, Wu L, Liu S, Miyata T, Song Q, Wei Q, Zhao C, Lin C, Yang J. Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Signal Transduct Target Ther 2022; 7:287. [PMID: 35963848 PMCID: PMC9376100 DOI: 10.1038/s41392-022-01119-3] [Citation(s) in RCA: 162] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 06/15/2022] [Accepted: 07/08/2022] [Indexed: 11/24/2022] Open
Abstract
Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, and fibrosis. Importantly, growing evidence elucidates that the disruption of the gut-liver axis and microbe-derived metabolites drive the pathogenesis of NAFL/NASH. Extracellular vesicles (EVs) act as a signaling mediator, resulting in lipid accumulation, macrophage and hepatic stellate cell activation, further promoting inflammation and liver fibrosis progression during the development of NAFL/NASH. Targeting gut microbiota or EVs may serve as new strategies for the treatment of NAFL/NASH. Finally, other mechanisms, such as cell therapy and genetic approaches, also have enormous therapeutic potential. Incorporating drugs with different mechanisms and personalized medicine may improve the efficacy to better benefit patients with NAFL/NASH.
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Affiliation(s)
- Xiaohan Xu
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, China
| | - Kyle L Poulsen
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA
| | - Lijuan Wu
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, China
- Innovation Center of Marine Drug Screening & Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Shan Liu
- Innovation Center of Marine Drug Screening & Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Tatsunori Miyata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Qiaoling Song
- Innovation Center of Marine Drug Screening & Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Qingda Wei
- School of Medicine, Zhengzhou University, Zhengzhou, China
| | - Chenyang Zhao
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, China
- Innovation Center of Marine Drug Screening & Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Chunhua Lin
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Jinbo Yang
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
- Innovation Center of Marine Drug Screening & Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
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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] [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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Zarei L, Farhad N, Abbasi A. All-Trans Retinoic Acid (atRA) effectively improves liver steatosis in a rabbit model of high fat induced liver steatosis. Arch Physiol Biochem 2022; 128:1010-1015. [PMID: 32202947 DOI: 10.1080/13813455.2020.1743725] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The aim of this study is to evaluate the role of All-Trans Retinoic Acid, the biologically active metabolite of retinoids, on liver steatosis in a rabbit model of high fat induced lever steatosis. 30 male rabbits were evaluated in 5 groups: group 1 treated with normal diet, group 2-5 included rabbit's groups 2 to 5 were fed on high cholesterol diet, group 2 received no drugs, group 3 received atorvastatin, group 4 received atRA, and group 5 received both the drugs. the liver was obtained for histopathological evaluation. oral administration of atRA, atorvastatin or their combination significantly decreased serum levels of total cholesterol, LDL, AST and ALT. atorvastatin slightly but atRA remarkably decreased liver steatosis where the difference was significant. atRA group showed the highest TAC and the lowest PCO concentrations. atRA can be effective in reducing liver steatosis and its antioxidant effect plays a crucial role in the process.HighlightsNon-alcoholic fatty liver disease (NAFLD) is the most common disorder of the liver in general population and is strongly associated with metabolic risk factors including hyperlipidaemia, obesity and diabetes.atRA is very effective in reducing liver steatosis and its antioxidant effect plays a crucial role in the process.we suggest focussing on other aspects of liver steatosis such as carbohydrate metabolism and insulin resistance in order to find better ways of controlling and treating liver steatosis.
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Affiliation(s)
- Leila Zarei
- Department of Anatomical Science, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Negin Farhad
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Ata Abbasi
- Department of Pathology, Urmia University of Medical Sciences, Urmia, Iran
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Combination Therapies for Nonalcoholic Fatty Liver Disease. J Pers Med 2022; 12:jpm12071166. [PMID: 35887662 PMCID: PMC9322793 DOI: 10.3390/jpm12071166] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 07/01/2022] [Accepted: 07/13/2022] [Indexed: 11/17/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered a highly prevalent disease associated with various co-morbidities that lead to socioeconomic burden. Despite large-scale investigation, no pharmacological treatment has been approved specifically for NAFLD to date. Lifestyle modifications and diet are regarded as highly beneficial for the management of NAFLD, albeit with poor compliance, thus rendering pharmacological treatment highly important. Based on the current failure to discover a “magic bullet” to treat all patients with NAFLD and considering the multifaceted pathophysiology of the disease, combination therapies may be considered to be a rational alternative approach. In this regard, several drug categories have been considered, including, but not limited to, lipid-lowering, anti-hypertensive, glucose-lowering, anti-obesity, anti-oxidant, anti-inflammatory and anti-fibrotic medications. The aim of this review is, in addition to summarizing some of the multiple factors contributing to the pathophysiology of NAFLD, to focus on the efficacy of pharmacological combinations on the management of NAFLD. This may provide evidence for a more personalized treatment of patients with NAFLD in the future.
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Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract 2022; 28:528-562. [PMID: 35569886 DOI: 10.1016/j.eprac.2022.03.010] [Citation(s) in RCA: 512] [Impact Index Per Article: 170.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/11/2022] [Accepted: 03/11/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders. METHODS The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RECOMMENDATION SUMMARY This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base. CONCLUSION NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.
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Affiliation(s)
- Kenneth Cusi
- Guideine and Algorithm Task Forces Co-Chair, Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida
| | - Scott Isaacs
- Guideline and Algorithm Task Forces Co-Chair, Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia
| | - Diana Barb
- University of Florida, Gainesville, Florida
| | - Rita Basu
- Division of Endocrinology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Sonia Caprio
- Yale University School of Medicine, New Haven, Connecticut
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama
| | | | - Jeffrey I Mechanick
- The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health at Mount Sinai Heart, Icahn School of Medicine at Mount Sinai
| | | | - Karl Nadolsky
- Michigan State University College of Human Medicine, Grand Rapids, Michigan
| | - Mary E Rinella
- AASLD Representative, University of Pritzker School of Medicine, Chicago, Illinois
| | - Miriam B Vos
- Center for Clinical and Translational Research, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Zobair Younossi
- AASLD Representative, Inova Medicine, Inova Health System, Falls Church, Virginia
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Padole P, Arora A, Sharma P, Chand P, Verma N, Kumar A. Saroglitazar for Nonalcoholic Fatty Liver Disease: A Single Centre Experience in 91 Patients. J Clin Exp Hepatol 2022; 12:435-439. [PMID: 35535066 PMCID: PMC9077151 DOI: 10.1016/j.jceh.2021.06.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 06/12/2021] [Indexed: 12/12/2022] Open
Abstract
Background Saroglitazar is a novel, dual peroxisome proliferator-activated receptors-α/γ agonist and is being investigated for the treatment of nonalcoholic fatty liver disease (NAFLD). Patients and methods Consecutive overweight (body mass index [BMI] >23 kg/m2) patients of NAFLD, diagnosed based on controlled attenuation parameter (CAP) >248 dB/m, and attending the outpatient department of a tertiary care centre in New Delhi, were enrolled. Patients with cirrhosis (liver stiffness measurement [LSM] >13.5 kPa) and those with concomitant liver disease due to other aetiologies (alcohol, viral, etc.) were excluded. All patients received saroglitazar 4 mg/day; in addition, they were advised to reduce weight and were counselled regarding diet and exercise. At 3-month follow-up, patients were categorized into those who were able to reduce ≥5% body weight and those who could n'ot, and both these groups were compared. Results A total of 91 patients (median age 45 years [range 18-66 years]; 81% men) were included in the study. The median BMI was 29.3 kg/m2 (range 23.6-42.2 kg/m2). The baseline median (range) aspartate transaminase, alanine transaminase, gamma glutamyl transferase, LSM and CAP values were 40 IU/dL (range 22-144 IU/dL), 48 IU/dL (range 13-164 IU/dL), 42 IU/dL (range 4-171 IU/dL), 6.7 kPa (range 3.6-13.1 kPa), and 308 dB/m (range 249-400 dB/m). All patients tolerated saroglitazar well. At 3-month, 57 patients (63%) were able to reduce ≥5% weight, whereas in the remaining 34 patients (37%), the weight reduction was <5% from baseline. Transaminases values improved in both the groups; however, LSM and CAP values improved only in patients who reduced weight. Conclusion In overweight patients with NAFLD, a 3-month therapy with saroglitazar is able to improve transaminases but not LSM and CAP values unless accompanied by weight reduction of at least 5%. Larger randomized controlled trials are needed to document the independent effect of saroglitazar in these patients.
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Key Words
- ALP, alkaline phosphatase
- ALT, alanine transaminase
- AST, aspartate transaminase
- BMI, body mass index
- CAP, controlled attenuation parameter
- DCGI, Drug Controller General of India
- FDA, Food and Drug Administration
- GGT, gamma glutamyl transferase
- HCV, hepatitis C virus
- IQR, interquartile range
- IU, international units
- LSM, liver stiffness measurement
- MAFLD, metabolic (dysfunction) associated fatty liver disease
- NAFLD
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- PPAR, peroxisome proliferator-activated receptor
- controlled attenuation parameter
- dB, decibels
- kPa, kilopascal
- obesity
- pPAR agonist
- saroglitazar
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Affiliation(s)
- Prateek Padole
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Prakash Chand
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Nishant Verma
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
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Shi Y, Fan J. Therapeutic developments in metabolic dysfunction-associated fatty liver disease. Chin Med J (Engl) 2022; 135:1009-1018. [PMID: 35234696 PMCID: PMC9276260 DOI: 10.1097/cm9.0000000000002091] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has become one of the most prevalent chronic liver diseases worldwide, bringing risk of multiorgan disfunctions including cardiovascular events, complications of cirrhosis, and even malignance. In terms of health burden management, screening patients with high risk of MAFLD and providing individual comprehensive treatment is critical. Although there are numerous agents entering clinical trials for MAFLD treatment every year, there is still no effective approved drug. The nomenclature of MAFLD highlighted the concomitant metabolic disorders and obesity. MAFLD patients with type 2 diabetes had higher risk of developing liver cirrhosis and cancer, and would benefit from anti-hyperglycemic agents; overweight and obese patients may benefit more from weight loss therapies; for patients with metabolic syndrome, individual comprehensive management is needed to reduce the risk of adverse outcomes. In this review, we introduced the current status and advances of the treatment of MAFLD based on weight loss, improving insulin resistance, and management of cardiometabolic disorders, in order to provide individualized therapy approaches for patients with MAFLD.
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Affiliation(s)
- Yiwen Shi
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
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Finer N. Weight loss interventions and nonalcoholic fatty liver disease: Optimizing liver outcomes. Diabetes Obes Metab 2022; 24 Suppl 2:44-54. [PMID: 34622555 DOI: 10.1111/dom.14569] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 09/29/2021] [Accepted: 09/30/2021] [Indexed: 12/11/2022]
Abstract
The growth in prevalence of obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) has become one of the most important global health challenges. The three chronic diseases are closely linked in their epidemiology and pathophysiology. Currently, weight loss is the most effective treatment for NAFLD (even in the minority of patients with NAFLD who do not have obesity) and is recommended in all national and international guidelines. Accumulating evidence has shown that weight loss, whether achieved by diet and lifestyle interventions, bariatric surgery or pharmacotherapy, can improve biomarkers of NAFLD, as well as prevent progression and, in some cases, reverse fibrosis. There is a dose dependency of weight loss with NAFLD improvement. Pharmacotherapy with antiobesity medications, alone or in combination with intensive lifestyle interventions or other weight-loss drugs, is closing the efficacy gap between diet and exercise and weight-loss surgery in efficacy at reversing obesity. Given the importance of providing effective weight-loss treatment to patients with NAFLD, weight management services need to be made increasingly available and embedded within hepatology services. This narrative review addresses the evidence that weight loss optimizes liver outcomes in people with NAFLD.
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Affiliation(s)
- Nick Finer
- National Centre for Cardiovascular Prevention and Outcomes, UCL Institute of Cardiovascular Science, London, UK
- Novo Nordisk A/S Vandtårnsvej, Søborg, Denmark
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Atefi M, Entezari MH, Vahedi H, Hassanzadeh A. Sesame Oil Ameliorates Alanine Aminotransferase, Aspartate Aminotransferase, and Fatty Liver Grade in Women with Nonalcoholic Fatty Liver Disease Undergoing Low-Calorie Diet: A Randomized Double-Blind Controlled Trial. Int J Clin Pract 2022; 2022:4982080. [PMID: 35685535 PMCID: PMC9159187 DOI: 10.1155/2022/4982080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 11/29/2021] [Indexed: 12/15/2022] Open
Abstract
Background The type and amount of dietary fats play an important role in fat accumulation in the liver. Sesame oil (SO) is a good source of monounsaturated acids (MUFAs) and polyunsaturated fatty acids (PUFAs). Objective This trial aimed at examining the effect of SO consumption on the levels of liver enzymes and the severity of fatty liver in women with nonalcoholic fatty liver disease (NAFLD) undergoing a weight loss diet. Methods This randomized, double-blind, controlled trial was carried out on 60 women with NAFLD. Subjects were randomly assigned to the SO group (n = 30) and sunflower oil (SFO) group (n = 30), each person consuming 30 grams of oil per day for 12 weeks. All the participants received a hypocaloric diet (-500 kcal/day) during the study. Fatty liver grade and liver enzymes were assessed at pre- and postintervention phases. Results 53 patients completed the study. Significant reductions in body weight, body mass index (BMI), waist circumference (WC), and fatty liver grade were observed in both groups (P < 0.05). Following SO, significant decreases in serum aspartate and alanine aminotransferases (AST and ALT) were observed. After adjusting for confounders, ALT, AST, and fatty liver grade of the SO group were significantly reduced compared to the SFO group (P < 0.05). However, the changes in serum alkaline phosphatase (ALP) were not significant (P > 0.05). Conclusions The desired effects of weight loss were reinforced by the consumption of SO through improving fatty liver severity and serum ALT and AST levels in NAFLD patients. Moreover, low-calorie diets may lead to favorable outcomes for NAFLD patients through mitigation of obesity and fatty liver grade.
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Affiliation(s)
- Masoumeh Atefi
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Hassan Entezari
- Food Security Research Centre and Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamid Vahedi
- Department of Gastroenterology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Akbar Hassanzadeh
- Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
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Albhaisi S, Sanyal AJ. Pharmacology of NASH. COMPREHENSIVE PHARMACOLOGY 2022:214-238. [DOI: 10.1016/b978-0-12-820472-6.00121-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Zhang TT, Wang Y, Zhang XW, Yang KY, Miao XQ, Zhao GH. MiR-200c-3p Regulates DUSP1/MAPK Pathway in the Nonalcoholic Fatty Liver After Laparoscopic Sleeve Gastrectomy. Front Endocrinol (Lausanne) 2022; 13:792439. [PMID: 35299961 PMCID: PMC8920964 DOI: 10.3389/fendo.2022.792439] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 01/21/2022] [Indexed: 12/12/2022] Open
Abstract
AIM Non-alcoholic fatty liver disease (NAFLD) is a health burden worldwide, which is closely related to obesity. The effect of sleeve gastrectomy (SG) on NAFLD is efficient, and the underlying mechanism remains unknown. Our study sought to investigate the mechanism of dual-specificity protein phosphatase 1 (DUSP1) expression regulation following the SG procedure in NAFLD patients and C57BL/6J mice via miR-200c-3p. METHODS The serum was extracted from NAFLD patients who underwent laparoscopic sleeve gastrectomy (LSG) and volunteers. Next, the correlation between miR-200c-3p and DUSP1 was identified in vitro. NAFLD mice were modelled by high-fat diets (HFD). The hepatic tissue expression levels of miR-200c-3p, DUSP1, phospho-extracellular regulated protein kinases1/2 (p-ERK1/2), phospho -p38 mitogen-activated protein kinases (p-p38), and phospho-c-Jun N-terminal kinases (p-JNK) induced by SG procedure were evaluated. RESULTS The SG procedure contributed to significant weight loss, reduced lipids in NAFLD patients and mice. The increased expression level of miR-200c-3p and reduced expression of DUSP1 were observed in NAFLD patients and mice (p<0.05). The reduced expression levels of miR-200c-3p and increased expression of DUSP1 were observed in patients and mice with NAFLD who underwent SG procedure. DUSP1 is a potential target of miR-200c-3p. CONCLUSIONS A novel mechanism was identified in which miR-200c-3p regulates the MAPK-dependent signals that are linked to the promotion of hepatosteatosis via DUSP1 after sleeve gastrectomy. The findings suggested that miR-200c-3p should be further explored as a potential target for the treatments of NAFLD.
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Affiliation(s)
- Tao-tao Zhang
- General Surgery, Dalian Municipal Central Hospital, Dalian, China
- General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Yong Wang
- General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Yong Wang, ; Xiang-wen Zhang,
| | - Xiang-wen Zhang
- General Surgery, Dalian Municipal Central Hospital, Dalian, China
- *Correspondence: Yong Wang, ; Xiang-wen Zhang,
| | - Ke-yu Yang
- General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Xiu-qin Miao
- General Surgery, Dalian Municipal Central Hospital, Dalian, China
| | - Guo-hua Zhao
- General Surgery, Dalian Municipal Central Hospital, Dalian, China
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Georgescu CE. Polycystic ovary syndrome and nonalcoholic fatty liver disease. POLYCYSTIC OVARY SYNDROME 2022:187-216. [DOI: 10.1016/b978-0-12-823045-9.00007-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Han MAT, Olivo R, Choi CJ, Pyrsopoulos N. De novo and recurrence of metabolic dysfunction-associated fatty liver disease after liver transplantation. World J Hepatol 2021; 13:1991-2004. [PMID: 35070003 PMCID: PMC8727208 DOI: 10.4254/wjh.v13.i12.1991] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 07/27/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new acronym adopted from the consensus of international experts. Given the increasing prevalence of MAFLD in pre-transplant settings, de novo and recurrent graft steatosis/MAFLD are common in post-transplant settings. The impact of graft steatosis on long-term outcomes is unclear. The current knowledge of incidence rate, risk factors, diagnosis, long-term outcomes, and management of graft steatosis (both de novo and recurrent) is discussed in this review.
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Affiliation(s)
- Ma Ai Thanda Han
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Raquel Olivo
- Department of Gastroenterology and Hepatology, Rutgers University, New Jersey Medical School, Newark, NJ 07103, United States
| | - Catherine J Choi
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101, United States
| | - Nikolaos Pyrsopoulos
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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Kisoh K, Sugahara G, Ogawa Y, Furukawa S, Ishida Y, Okanoue T, Kohara M, Tateno C. Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers. Biomedicines 2021; 9:1647. [PMID: 34829876 PMCID: PMC8615377 DOI: 10.3390/biomedicines9111647] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/03/2021] [Accepted: 11/03/2021] [Indexed: 01/09/2023] Open
Abstract
Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is the most common liver disorder in developed countries. Although many new therapeutics for NASH are present in the drug development pipeline, there are still no approved drugs. One of the reasons that makes NASH drug development challenging is the lack of appropriate animal NASH models that resolve issues arising from inter-species differences between humans and rodents. In the present study, we developed a choline-deficient, L-amino-acid-defined, high-fat-diet (CDAHFD)-induced human NASH model using human liver chimeric mice. We demonstrated human hepatocyte injury by an elevation of plasma human alanine aminotransferase 1 in mice fed CDAHFD. Histological analysis showed that CDAHFD feeding induced similar histological changes to human NASH patients, including ballooning, inflammation, apoptosis, regeneration of human hepatocytes, and pericellular and perisinusoidal fibrosis. The chimeric mice fed CDAHFD were treated with a peroxisome-proliferator-activated receptor α/δ agonist, Elafibranor. Elafibranor ameliorated steatosis, ballooning of hepatocytes, and preserved fibrosis progression. We developed a novel humanized NASH model that can elucidate pathophysiological mechanisms and predict therapeutic efficacy in human NASH. This model will be useful in exploring new drugs and biomarkers in the early stages of human NASH.
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Affiliation(s)
- Keishi Kisoh
- Research and Development Department, PhoenixBio Co., Ltd., 3-4-1 Kagamiyama, Higashihiroshima 739-0046, Japan; (K.K.); (G.S.); (Y.O.); (S.F.); (Y.I.)
| | - Go Sugahara
- Research and Development Department, PhoenixBio Co., Ltd., 3-4-1 Kagamiyama, Higashihiroshima 739-0046, Japan; (K.K.); (G.S.); (Y.O.); (S.F.); (Y.I.)
| | - Yuko Ogawa
- Research and Development Department, PhoenixBio Co., Ltd., 3-4-1 Kagamiyama, Higashihiroshima 739-0046, Japan; (K.K.); (G.S.); (Y.O.); (S.F.); (Y.I.)
| | - Suzue Furukawa
- Research and Development Department, PhoenixBio Co., Ltd., 3-4-1 Kagamiyama, Higashihiroshima 739-0046, Japan; (K.K.); (G.S.); (Y.O.); (S.F.); (Y.I.)
| | - Yuji Ishida
- Research and Development Department, PhoenixBio Co., Ltd., 3-4-1 Kagamiyama, Higashihiroshima 739-0046, Japan; (K.K.); (G.S.); (Y.O.); (S.F.); (Y.I.)
- Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazonocho, Suita 564-0013, Japan;
| | - Michinori Kohara
- Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan;
| | - Chise Tateno
- Research and Development Department, PhoenixBio Co., Ltd., 3-4-1 Kagamiyama, Higashihiroshima 739-0046, Japan; (K.K.); (G.S.); (Y.O.); (S.F.); (Y.I.)
- Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
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Abstract
With the recent urbanization and globalization, the adult obesity rate has been increasing, which was paralleled with a dramatic surge in the incidence and prevalence of nonalcoholic fatty liver disease (NAFLD). NAFLD poses a growing threat to human health as it represents the most common cause of chronic liver disease in developed countries. It encompasses a wide spectrum of conditions starting from a build-up of fat in hepatocytes (steatosis), to developing inflammation (steatohepatitis), and reaching up to cirrhosis. It is also associated with higher rates of cardiovascular mortalities. Therefore, proper timely treatment is essential and weight loss remains the cornerstone in the treatment of obesity-related liver diseases. When diet, exercise, and lifestyle changes are not successful, the current recommendation for weight loss includes antiobesity medications and bariatric endoscopic and surgical interventions. These interventions have shown to result in significant weight loss and improve liver steatosis and fibrosis. In the current literature review, we highlight the expected outcomes and side effects of the currently existing options to have a weight-centric NAFLD approach.
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Affiliation(s)
- Anas Hashem
- Division of Gastroenterology and Hepatology, Department of Medicine, Precision Medicine for Obesity Program, Mayo Clinic, Rochester, Minnesota
| | - Amani Khalouf
- Division of Gastroenterology and Hepatology, Department of Medicine, Precision Medicine for Obesity Program, Mayo Clinic, Rochester, Minnesota
| | - Andres Acosta
- Division of Gastroenterology and Hepatology, Department of Medicine, Precision Medicine for Obesity Program, Mayo Clinic, Rochester, Minnesota
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Satiya J, Snyder HS, Singh SP, Satapathy SK. Narrative review of current and emerging pharmacological therapies for nonalcoholic steatohepatitis. Transl Gastroenterol Hepatol 2021; 6:60. [PMID: 34805582 PMCID: PMC8573363 DOI: 10.21037/tgh-20-247] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 09/25/2020] [Indexed: 12/28/2022] Open
Abstract
Nonalcoholic steatohepatitis (NASH) is the most common cause of chronic liver disease today, and it has now emerged as the leading etiology of end-stage liver disease requiring liver transplantation. It is a progressive form of non-alcoholic fatty liver disease which can not only progress to cirrhosis of liver and hepatocellular carcinoma (HCC), but is associated with increased cardiovascular risks too. Despite all the advances in the understanding of the risk factors and the pathogenetic pathways involved in the pathogenesis and progression of NASH, an effective therapy for NASH has not been developed yet. Although lifestyle modifications including dietary modifications and physical activity remain the mainstay of therapy, there is an unmet need to develop a drug or a combination of drugs which can not only reduce the fatty infiltration of the liver, but also arrest the development and progression of fibrosis and advancement to cirrhosis of liver and HCC. The pharmacologic therapies which are being developed target the various components believed to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)/NASH which includes insulin resistance, lipid metabolism oxidative stress, lipid peroxidation, inflammatory and cell death pathways, and fibrosis. In this review, we summarize the current state of knowledge on pharmacotherapy of NASH, and also highlight the recent developments in the field, for optimizing the management and treatment of NASH.
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Affiliation(s)
- Jinendra Satiya
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | | | - Shivaram Prasad Singh
- Department of Gastroenterology, S.C.B. Medical College, Cuttack, India
- Kalinga Gastroenterology Foundation, Beam Diagnostics Centre, Cuttack, India
| | - Sanjaya K. Satapathy
- Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Northwell Health, Manhasset, NY, USA
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Czarnecka K, Czarnecka P, Tronina O, Bączkowska T, Durlik M. Multidirectional facets of obesity management in the metabolic syndrome population after liver transplantation. IMMUNITY INFLAMMATION AND DISEASE 2021; 10:3-21. [PMID: 34598315 PMCID: PMC8669703 DOI: 10.1002/iid3.538] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/26/2021] [Accepted: 09/14/2021] [Indexed: 12/13/2022]
Abstract
The obesity pandemic has resulted in an increasing demand for liver transplantation and has significantly altered the profile of liver transplant candidates in addition to affecting posttransplantation outcomes. In this review, we discuss a broad range of clinical approaches that warrant attention to provide comprehensive and patient‐centred medical care to liver transplant recipients, and to be prepared to confront the rapidly changing clinical challenges and ensuing dilemmas. Adipose tissue is a complex and metabolically active organ. Visceral fat deposition is a key predictor of overall obesity‐related morbidity and mortality. Limited pharmacological options are available for the treatment of obesity in the liver transplant population. Bariatric surgery may be an alternative in eligible patients. The rapidly increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global concern; NAFLD affects both pre‐ and posttransplantation outcomes. Numerous studies have investigated pharmacological and nonpharmacological management of NAFLD and some of these have shown promising results. Liver transplant recipients are constantly exposed to numerous factors that result in intestinal microbiota alterations, which were linked to the development of obesity, diabetes type 2, metabolic syndrome (MS), NAFLD, and hepatocellular cancer. Microbiota modifications with probiotics and prebiotics bring gratifying results in the management of metabolic complications. Fecal microbiota transplantation (FMT) is successfully performed in many medical indications. However, the safety and efficacy profiles of FMT in immunocompromised patients remain unclear. Obesity together with immunosuppressive treatment, may affect the pharmacokinetic and/or pharmacodynamic properties of coadministered medications. Individualized immunosuppressive regimens are recommended following liver transplantation to address possible metabolic concerns. Effective and comprehensive management of metabolic complications is shown to yield multiple beneficial results in the liver transplant population and may bring gratifying results in improving long‐term survival rates.
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Affiliation(s)
- Kinga Czarnecka
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Paulina Czarnecka
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Olga Tronina
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Teresa Bączkowska
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Magdalena Durlik
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
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Garcinia cambogia Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation. Antioxidants (Basel) 2021; 10:antiox10081226. [PMID: 34439474 PMCID: PMC8388869 DOI: 10.3390/antiox10081226] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 07/28/2021] [Indexed: 12/14/2022] Open
Abstract
Excessive free fatty acids (FFAs) causes reactive oxygen species (ROS) generation and non-alcoholic fatty liver disease (NAFLD) development. Garcinia cambogia (G. cambogia) is used as an anti-obesity supplement, and its protective potential against NAFLD has been investigated. This study aims to present the therapeutic effects of G. cambogia on NAFLD and reveal underlying mechanisms. High-fat diet (HFD)-fed mice were administered G. cambogia for eight weeks, and steatosis, apoptosis, and biochemical parameters were examined in vivo. FFA-induced HepG2 cells were treated with G. cambogia, and lipid accumulation, apoptosis, ROS level, and signal alterations were examined. The results showed that G. cambogia inhibited HFD-induced steatosis and apoptosis and abrogated abnormalities in serum chemistry. G. cambogia increased in NRF2 nuclear expression and activated antioxidant responsive element (ARE), causing induction of antioxidant gene expression. NRF2 activation inhibited FFA-induced ROS production, which suppressed lipogenic transcription factors, C/EBPα and PPARγ. Moreover, the ability of G. cambogia to inhibit ROS production suppressed apoptosis by normalizing the Bcl-2/BAX ratio and PARP cleavage. Lastly, these therapeutic effects of G. cambogia were due to hydroxycitric acid (HCA). These findings provide new insight into the mechanism by which G. cambogia regulates NAFLD progression.
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