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Wang D, Miao J, Zhang L, Zhang L. Research advances in the diagnosis and treatment of MASLD/MASH. Ann Med 2025; 57. [DOI: 10.1080/07853890.2024.2445780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/01/2024] [Accepted: 12/02/2024] [Indexed: 01/06/2025] Open
Affiliation(s)
- Dekai Wang
- Department of General Practice, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jinxian Miao
- Department of General Practice, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Lihua Zhang
- Department of General Practice, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Lin Zhang
- Department of General Practice, The First Affiliated Hospital of Kunming Medical University, Kunming, China
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2
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Franco I, Bianco A, Bonfiglio C, Curci R, Campanella A, Osella AR. Leisure-Time Physical Activity, Time Spent Sitting and Risk of Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study in Puglia. J Gen Intern Med 2024; 39:2788-2796. [PMID: 38806797 PMCID: PMC11534907 DOI: 10.1007/s11606-024-08804-9] [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: 01/16/2024] [Accepted: 05/07/2024] [Indexed: 05/30/2024]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. The increasingly sedentary lifestyle in recent years may have accelerated the development of NAFLD, independent of the level of physical activity. OBJECTIVE The purpose of this cross-sectional study was to determine the association between leisure-time physical activity (LTPA) and time spent sitting (TSS) and the likelihood of developing NAFLD in a sample of men and women aged 18-64 years, from southern Italy. DESIGN The study is based on two cohort studies, a randomized clinical trial and an observational cost-benefit study. PARTICIPANTS A total of 1269 participants (51.5% women) drawn from 3992 eligible subjects were enrolled in this study. EXPOSURES Leisure-time physical activity (LTPA) and time spent sitting (TSS) were assessed using the Italian long form of the International Physical Activity Questionnaire (IPAQ-LF), designed for administration to adults aged 18 to 65 years. MAIN MEASURES The association of exposures with the probability of belonging to a certain NAFLD degree of severity. KEY RESULTS The probability of having mild, moderate, and severe NAFLD tends to decrease with increasing LTPA and decreasing TSS levels. We selected a combination of participants aged 50 years and older stratified by gender. Men had a statistically significant difference in the probability of developing moderate NAFLD if they spent 70 h per week sitting and had low LTPA, while among women there was a statistically significant difference in the probability of developing mild or moderate NAFLD if they had moderate LPTA and spent 35-70 h/week sitting. CONCLUSIONS The study thus showed that the amount of LTPA and the amount of TSS are associated with development and progression of NAFLD, but this relationship is not a linear one-especially in women aged ≥ 50 years old.
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Affiliation(s)
- Isabella Franco
- National Institute of Gastroenterology-IRCCS "S. de Bellis", Castellana Grotte, Italy.
| | - Antonella Bianco
- National Institute of Gastroenterology-IRCCS "S. de Bellis", Castellana Grotte, Italy
| | - Caterina Bonfiglio
- National Institute of Gastroenterology-IRCCS "S. de Bellis", Castellana Grotte, Italy
| | - Ritanna Curci
- National Institute of Gastroenterology-IRCCS "S. de Bellis", Castellana Grotte, Italy
| | - Angelo Campanella
- National Institute of Gastroenterology-IRCCS "S. de Bellis", Castellana Grotte, Italy
| | - Alberto Rubén Osella
- Estadìstica y Bioestadìstica Escuela de Nutriciòn, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
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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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Xue Y, Peng Y, Zhang L, Ba Y, Jin G, Liu G. Effect of different exercise modalities on nonalcoholic fatty liver disease: a systematic review and network meta-analysis. Sci Rep 2024; 14:6212. [PMID: 38485714 PMCID: PMC10940706 DOI: 10.1038/s41598-024-51470-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 01/05/2024] [Indexed: 03/18/2024] Open
Abstract
Physical exercise intervention can significantly improve the liver of patients with Non-alcoholic fatty liver disease (NAFLD), but it is unknown which exercise mode has the best effect on liver improvement in NAFLD patients. Therefore, we systematically evaluated the effect of exercise therapy on liver and blood index function of NAFLD patients through network meta-analysis (NMA). Through systematic retrieval of PubMed, Cochrane Library, Web of Science, EBSCO, and CNKI (National Knowledge Infrastructure), two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies by means of databases from inception to January 2023. The NMA was performed using the inconsistency model. A total of 43 studies, 2070 NAFLD patients were included: aerobic training (n = 779), resistance training (n = 159), high-intensity interval training (n = 160), aerobic training + resistance training (n = 96). The results indicate that aerobic training + resistance training could significantly improve serum total cholesterol (TC) (Surface under the cumulative ranking curve (SUCRA) = 71.7), triglyceride (TG) (SUCRA = 96.8), low-density lipoprotein cholesterol (LDL-C) (SUCRA = 86.1) in patients with NAFLD including triglycerides. Aerobic training is the best mode to improve ALT (SUCRA = 83.9) and high-density lipoprotein cholesterol (HDL-C) (SUCRA = 72.3). Resistance training is the best mode to improve aspartate transaminase (AST) (SUCRA = 81.7). Taking various benefits into account, we believe that the best modality of exercise for NAFLD patients is aerobic training + resistance training. In our current network meta-analysis, these exercise methods have different effects on the six indicators of NAFLD, which provides some reference for further formulating exercise prescription for NAFLD patients.
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Affiliation(s)
- Yaqi Xue
- Beijing Normal University College of Physical Education and Sport, Beijing, China
| | - Yang Peng
- Physical Education Department, Northeastern University, Shenyang, Liaoning, China
| | | | - Yi Ba
- Beijing Normal University College of Physical Education and Sport, Beijing, China
| | - Gang Jin
- Physical Education Department, Northeastern University, Shenyang, Liaoning, China
| | - Ge Liu
- School of Economics and Management, Hebei University of Architecture, Hebei, China.
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5
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Gupta U, Ruli T, Buttar D, Shoreibah M, Gray M. Metabolic dysfunction associated steatotic liver disease: Current practice, screening guidelines and management in the primary care setting. Am J Med Sci 2024; 367:77-88. [PMID: 37967750 DOI: 10.1016/j.amjms.2023.11.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/29/2023] [Accepted: 11/10/2023] [Indexed: 11/17/2023]
Abstract
Metabolic dysfunction associated steatotic liver disease, previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease in the United States with rapidly rising prevalence. There have been significant changes recently in the field with screening now recommended for patients at risk for significant liver fibrosis in primary care and endocrine settings, along with clear guidance for management of metabolic comorbidities and changes in nomenclature. This paper serves as a summary of recent guidance for the primary care physician focusing on identifying appropriate patients for screening, selecting suitable screening modalities, and determining when referral to specialty care is necessary. The hope is that providers will shift away from past practices of utilizing liver tests alone as a screening tool and shift towards fibrosis screening in patients at risk for significant fibrosis. This culture change will allow for earlier identification of patients at risk for end stage liver disease and serious liver related complications, and overall improved patient care.
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Affiliation(s)
- Udita Gupta
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Thomas Ruli
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Danyaal Buttar
- Department of Medicine, Campbell University School of Medicine, NC, USA
| | - Mohamed Shoreibah
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Meagan Gray
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
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Baek KW, Won JH, Xiang YY, Woo DK, Park Y, Kim JS. Exercise intensity impacts the improvement of metabolic dysfunction-associated steatotic liver disease via variations of monoacylglycerol O-acyltransferase 1 expression. Clin Res Hepatol Gastroenterol 2024; 48:102263. [PMID: 38061546 DOI: 10.1016/j.clinre.2023.102263] [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: 11/06/2023] [Revised: 12/01/2023] [Accepted: 12/05/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND The involvement of monoacylglycerol O-acyltransferase 1 (MOGAT1) in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) has been recognized. While exercise is recommended for the improvement of obesity and MASLD, the impact of exercise intensity remains unclear. This study aimed to examine the influence of exercise intensity on MOGAT1 expression in high-fat diet (HFD)-induced obese mice with MASLD. METHOD Male C57BL/6 mice aged 6 weeks were subjected to either a regular or HFD with 60 % fat content for 8 weeks. The mice were categorized into 5 groups based on their diet and exercise intensity: normal diet group (ND), HFD group, low-intensity exercise with HFD group (HFD+LIE), moderate-intensity exercise with HFD group (HFD+MIE), and high-intensity exercise (HIE) with HFD group (HFD+HIE). The duration of running was adjusted to ensure uniform exercise load across groups (total distance = 900 m): HFD+LIE at 12 m/min for 75 min, HFD+MIE at 15 m/min for 60 min, and HFD+HIE at 18 m/min for 50 min. RESULTS Lipid droplet size and MASLD activity score were significantly lower in the HFD+HIE group compared to other exercise-intensity groups (p < 0.05). Among the 3 intensity exercise groups, the lowest MOGAT1 protein expression was found in the HFD+HIE group (p < 0.05). CONCLUSION This study reveals that high-intensity exercise has the potential to mitigate MASLD development, partly attributed to the downregulation of MOGAT1 expression.
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Affiliation(s)
- Kyung-Wan Baek
- Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828, Korea; Department of Physical Education, Gyeongsang National University, Jinju, 52828, Korea
| | - Jong-Hwa Won
- Department of Physical Education, Gyeongsang National University, Jinju, 52828, Korea
| | - Ying-Ying Xiang
- Department of Physical Education, Gyeongsang National University, Jinju, 52828, Korea
| | - Dong Kyun Woo
- Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828, Korea; College of Pharmacy, Gyeongsang National University, Jinju, 52828, Korea
| | - Yoonjung Park
- Department of Health and Human Performance, University of Houston, Houston, 77204, USA
| | - Ji-Seok Kim
- Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828, Korea; Department of Physical Education, Gyeongsang National University, Jinju, 52828, Korea; Department of Health and Human Performance, University of Houston, Houston, 77204, USA.
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Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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A Chagas L, Torloni MR, Sanchez VHS, Pititto BA, Dualib PM, Mattar R. Dietary intake of pregnant women with non-alcoholic fatty liver disease: A case-control study. Clin Nutr ESPEN 2023; 57:630-636. [PMID: 37739716 DOI: 10.1016/j.clnesp.2023.08.018] [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: 12/20/2022] [Revised: 07/20/2023] [Accepted: 08/16/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND AND AIMS Findings on the role of diet in non-alcoholic fatty liver disease (NAFLD) pathogenesis are inconsistent. There are few studies on the dietary habits of pregnant women with NAFLD. Our primary aim was to compare the dietary intakes of pregnant women with and without NAFLD. METHODS This case-control study recruited 60 women (26-34 weeks' gestation) with recently diagnosed gestational diabetes (GDM) before any treatment was implemented. At recruitment, all participants underwent B-mode hepatic ultrasound. We included 30 women with sonographic NAFLD (cases) and 30 women without NAFLD (controls) matched for age, skin color, and pre-pregnancy body mass index. We assessed participants' dietary intakes in the last six months using a validated food frequency questionnaire. Mann-Whitney´s test was used to compare differences in median macro and micronutrient intakes between cases and controls. RESULTS Total median daily energy (1965.1 × 1949.2 calories) and lipid (25.1% × 28.3%) intakes were similar in women with and without NAFLD and fell within recommended ranges. Participants with NAFLD reported significantly higher median daily intakes of carbohydrates (59.4% × 53.1% p = 0.003), and significantly lower protein (15.6% × 17.0% p = 0.005), fiber (10.7 × 13.3 g/day p = 0.010), and vitamin C (151.8 × 192.6 mg/day p = 0.008) intakes than those without NAFLD. CONCLUSIONS Pregnant women with NAFLD ingest more carbohydrates and less protein, fiber, and vitamin C than those without NAFLD. Our findings contribute to understanding the role of diet in the development of NAFLD in pregnant women.
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Affiliation(s)
- Lucas A Chagas
- Department of Obstetrics, São Paulo Federal University, Rua Napoleão de Barros, 875, São Paulo - SP, 04024-002, Brazil
| | - Maria R Torloni
- Department of Obstetrics, São Paulo Federal University, Rua Napoleão de Barros, 875, São Paulo - SP, 04024-002, Brazil; Evidence Based Health Care Post-Graduate Program, Department of Medicine, São Paulo Federal University, Rua Botucatu 740, 3º andar, São Paulo - SP, 04023-900, Brazil.
| | - Victor H S Sanchez
- Department of Obstetrics, São Paulo Federal University, Rua Napoleão de Barros, 875, São Paulo - SP, 04024-002, Brazil
| | - Bianca A Pititto
- Department of Endocrinology, São Paulo Federal University, Rua Borges de Lagoa, 800, São Paulo - SP, 04038-001, São Paulo, Brazil
| | - Patrícia M Dualib
- Department of Endocrinology, São Paulo Federal University, Rua Borges de Lagoa, 800, São Paulo - SP, 04038-001, São Paulo, Brazil
| | - Rosiane Mattar
- Department of Obstetrics, São Paulo Federal University, Rua Napoleão de Barros, 875, São Paulo - SP, 04024-002, Brazil
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Niemelä O, Bloigu A, Bloigu R, Aalto M, Laatikainen T. Associations between Liver Enzymes, Lifestyle Risk Factors and Pre-Existing Medical Conditions in a Population-Based Cross-Sectional Sample. J Clin Med 2023; 12:4276. [PMID: 37445311 DOI: 10.3390/jcm12134276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/20/2023] [Accepted: 06/24/2023] [Indexed: 07/15/2023] Open
Abstract
While alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) enzymes are commonly used indicators of liver dysfunction recent studies have suggested that these may also serve as predictive biomarkers in the assessment of extrahepatic morbidity. In order to shed further light on the interactions between serum liver enzyme abnormalities, factors of lifestyle and health status we examined ALT and GGT activities in a population-based sample of 8743 adult individuals (4048 men, 4695 women from the National FINRISK 2002 Study, mean age 48.1 ± 13.1 years) with different levels of alcohol drinking, smoking, physical activity, body weight and the presence or absence of various pre-existing medical conditions. The assessments also included laboratory tests for inflammation, lipid status and fatty liver index (FLI), a proxy for fatty liver. The prevalence of ALT and GGT abnormalities were significantly influenced by alcohol use (ALT: p < 0.0005 for men; GGT: p <0.0005 for both genders), smoking (GGT: p <0.0005 for men, p =0.002 for women), adiposity (p < 0.0005 for all comparisons), physical inactivity (GGT: p <0.0005; ALT: p <0.0005 for men, p <0.05 for women) and coffee consumption (p <0.0005 for GGT in both genders; p <0.001 for ALT in men). The total sum of lifestyle risk factor scores (LRFS) influenced the occurrence of liver enzyme abnormalities in a rather linear manner. Significantly higher LRFS were observed in the subgroups of individuals with pre-existing medical conditions when compared with those having no morbidities (p <0.0005). In logistic regression analyses adjusted for the lifestyle factors, both ALT and GGT associated significantly with fatty liver, diabetes and hypertension. GGT levels also associated with coronary heart disease, angina pectoris, cardiac insufficiency, cerebrovascular disease, asthma and depression. Combinations of abnormal ALT and GGT activities significantly increased the odds for hypertension coinciding with abnormalities in biomarkers of inflammation, lipid status and FLI. The data indicates that ALT and GGT activities readily respond to unfavorable factors of lifestyle associating also with a wide array of pre-existing medical conditions. The data supports close links between both hepatic and extrahepatic morbidities and lifestyle risk factors and may open new insights on a more comprehensive use of liver enzymes in predictive algorithms for assessing mechanistically anchored disease conditions.
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Affiliation(s)
- Onni Niemelä
- Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital and Tampere University, 60220 Seinäjoki, Finland
| | - Aini Bloigu
- Research Unit of Population Health, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland
| | - Risto Bloigu
- Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland
| | - Mauri Aalto
- Department of Psychiatry, Seinäjoki Central Hospital and Tampere University, 33100 Tampere, Finland
| | - Tiina Laatikainen
- Department of Public Health and Social Welfare, Finnish Institute for Health and Welfare (THL), 00271 Helsinki, Finland
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland
- Joint Municipal Authority for North Karelia Social and Health Services, 80210 Joensuu, Finland
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Abstract
The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment.
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Affiliation(s)
- Onni Niemelä
- Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital and Tampere University, Seinäjoki, Finland.
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Noureddin M, Abdelmalek MF. Current Treatment Options, Including Diet, Exercise, and Medications: The Impact on Histology. Clin Liver Dis 2023; 27:397-412. [PMID: 37024215 DOI: 10.1016/j.cld.2023.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Paralleling the rise in obesity and diabetes, nonalcoholic fatty liver disease (NAFLD) is now the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, may progress to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Despite its public health treat, no approved pharmacotherapies for NAFLD/NASH currently exist. Although the armamentarium of therapies for NASH is limited, current treatment options include life-style modification and the use of medications to treat metabolic comorbidities. This review addresses current approaches to the treatment of NAFLD/NASH, including the impact of diet, exercise, and available pharmacotherapies on the histologic features of liver injury.
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Affiliation(s)
- Mazen Noureddin
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA; Houston Research Institute and Houston Liver Institute, Houston, TX, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology & Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
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Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, Kleiner DE, Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 2023; 77:1797-1835. [PMID: 36727674 PMCID: PMC10735173 DOI: 10.1097/hep.0000000000000323] [Citation(s) in RCA: 955] [Impact Index Per Article: 477.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 01/18/2023] [Indexed: 02/03/2023]
Affiliation(s)
- Mary E. Rinella
- University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA
| | | | | | | | - Stephen Caldwell
- School of Medicine, University of Virginia, Charlottesville, Virginia, USA
| | - Diana Barb
- University of Florida College of Medicine, Gainesville, Florida, USA
| | | | - Rohit Loomba
- University of California, San Diego, San Diego, California, USA
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Alomari M, Rashid MU, Chadalavada P, Ragheb J, Zafar H, Suarez ZK, Khazaaleh S, Gonzalez AJ, Castro FJ. Comparison between metabolic-associated fatty liver disease and nonalcoholic fatty liver disease: From nomenclature to clinical outcomes. World J Hepatol 2023; 15:477-496. [PMID: 37206648 PMCID: PMC10190689 DOI: 10.4254/wjh.v15.i4.477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/04/2023] [Accepted: 03/22/2023] [Indexed: 04/20/2023] Open
Abstract
As a result of the obesity epidemic, Nonalcoholic fatty liver disease (NAFLD) and its complications have increased among millions of people. Consequently, a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis; metabolic-associated fatty liver disease (MAFLD). This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD. This article discusses the rationale behind the nomenclature change, the main differences, and its clinical implications.
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Affiliation(s)
- Mohammad Alomari
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States.
| | - Mamoon Ur Rashid
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Pravallika Chadalavada
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Jonathan Ragheb
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Hammad Zafar
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Zoilo Karim Suarez
- Department of Internal Medicine, Florida Atlantic University Charles E Schmidt College of Medicine, Boca Raton, FL 33431, United States
| | - Shrouq Khazaaleh
- Department of Internal Medicine, Cleveland Clinic Fairview Hospital, Cleveland, OH 44126, United States
| | - Adalberto Jose Gonzalez
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Fernando J Castro
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL 33331, United States
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Hejazi K, Hackett D. Effect of Exercise on Liver Function and Insulin Resistance Markers in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med 2023; 12:jcm12083011. [PMID: 37109347 PMCID: PMC10143548 DOI: 10.3390/jcm12083011] [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: 03/16/2023] [Revised: 04/16/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Structured exercise as part of lifestyle modification plays an important role in the improvement of non-alcoholic fatty liver disease (NAFLD); however, its effectiveness has been shown to vary. This systematic review with meta-analysis investigated the effects of exercise on liver function and insulin resistance markers in patients with NAFLD. METHODS Six electronic databases were searched using terms related to exercise and NAFLD up to March 2022. Data were analyzed using a random-effects model to estimate the standardized mean difference (SMD) and 95% confidence interval. RESULTS The systematic search identified 2583 articles, of which a total of 26 studies met the inclusion criteria and were eligible. Exercise training had a moderate effect on reducing ALT (SMD: -0.59, p = 0.01) and small effects on reducing AST (SMD: -0.40, p = 0.01) and insulin (SMD: -0.43, p = 0.02). Significant reductions in ALT were found following aerobic training (SMD: -0.63, p < 0.01) and resistance training (SMD: -0.45, p < 0.001). Moreover, reductions in AST were found following resistance training (SMD: -0.54, p = 0.001), but not after aerobic training and combined training. However, reductions in insulin were found following aerobic training (SMD: -0.55, p = 0.03). Exercise interventions for <12 weeks compared to ≥12 weeks were more effective in reducing FBG and HOMA-IR, while interventions for ≥12 weeks compared to <12 weeks were more effective in reducing ALT and AST levels. CONCLUSIONS Our findings support the effectiveness of exercise in improving liver function markers but not in blood glucose control in NAFLD patients. Additional studies are needed to determine the exercise prescription to maximize health in these patients.
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Affiliation(s)
- Keyvan Hejazi
- Department of Physical Education and Sport Sciences, Hakim Sabzevari University, Sabzevar 9617976487, Iran
| | - Daniel Hackett
- Discipline of Exercise & Sport Science, Health and Performance Faculty Research Group, Faculty of Medicine and Health, Sydney School of Health Sciences, The University of Sydney, Camperdown, NSW 2006, Australia
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15
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Tsamos G, Vasdeki D, Koufakis T, Michou V, Makedou K, Tzimagiorgis G. Therapeutic Potentials of Reducing Liver Fat in Non-Alcoholic Fatty Liver Disease: Close Association with Type 2 Diabetes. Metabolites 2023; 13:metabo13040517. [PMID: 37110175 PMCID: PMC10141666 DOI: 10.3390/metabo13040517] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 03/21/2023] [Accepted: 03/29/2023] [Indexed: 04/29/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most widespread chronic liver disease worldwide, confers a significant burden on health systems and leads to increased mortality and morbidity through several extrahepatic complications. NAFLD comprises a broad spectrum of liver-related disorders, including steatosis, cirrhosis, and hepatocellular carcinoma. It affects almost 30% of adults in the general population and up to 70% of people with type 2 diabetes (T2DM), sharing common pathogenetic pathways with the latter. In addition, NAFLD is closely related to obesity, which acts in synergy with other predisposing conditions, including alcohol consumption, provoking progressive and insidious liver damage. Among the most potent risk factors for accelerating the progression of NAFLD to fibrosis or cirrhosis, diabetes stands out. Despite the rapid rise in NAFLD rates, identifying the optimal treatment remains a challenge. Interestingly, NAFLD amelioration or remission appears to be associated with a lower risk of T2DM, indicating that liver-centric therapies could reduce the risk of developing T2DM and vice versa. Consequently, assessing NAFLD requires a multidisciplinary approach to identify and manage this multisystemic clinical entity early. With the continuously emerging new evidence, innovative therapeutic strategies are being developed for the treatment of NAFLD, prioritizing a combination of lifestyle changes and glucose-lowering medications. Based on recent evidence, this review scrutinizes all practical and sustainable interventions to achieve a resolution of NAFLD through a multimodal approach.
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Affiliation(s)
- Georgios Tsamos
- Division of Gastroenterology, Norfolk and Norwich University Hospital, Norwich NR4 7UY, UK
| | - Dimitra Vasdeki
- Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
| | - Theocharis Koufakis
- Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
| | - Vassiliki Michou
- Sports Medicine Laboratory, School of Physical Education & Sport Science, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece
| | - Kali Makedou
- Laboratory of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
| | - Georgios Tzimagiorgis
- Laboratory of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
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16
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Masrour O, Bardou-Jacquet E. Traitement médical de la stéatohépatite métabolique en 2022. NUTR CLIN METAB 2023. [DOI: 10.1016/j.nupar.2022.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
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17
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Nandula SR, Nylen ES, Sen S. Novel Therapeutics in Nonalcoholic Fatty Liver Disease: A Focus on Adult Stem Cells. Metab Syndr Relat Disord 2023; 21:71-78. [PMID: 36625898 DOI: 10.1089/met.2022.0069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder that is associated with abnormal accumulation of fat in the liver, which can lead to a wide variety of pathological liver defects and associated insulin resistance (IR), obesity, hypertension, dyslipidemia, diabetes, and cardiovascular disease. The molecular mechanisms that cause the initiation and progression of NAFLD are not fully understood. Increased lipolysis and de novo hepatic lipid synthesis lead to oxidative stress induced by reactive oxygen species and inflammation. Both these two entities could be interrelated and be an important mechanistic pathway, which can lead to tissue injury and hepatic cell death. Mechanisms for worsening of NAFLD include mitochondrial abnormalities, downregulation of glutathione (GSH), decreased activity of GSH-dependent antioxidants, accumulation of activated macrophages, hepatic inflammation, systemic inflammation, IR, and poorly controlled type 2 diabetes mellitus. Although no specific therapy has been approved for NAFLD, we review the latest medical therapeutics with emphasis on stem cell-based possibilities based on the presumed pathophysiology of NAFLD.
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Affiliation(s)
- Seshagiri Rao Nandula
- Division of Endocrinology, Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA.,Department of Biochemistry and Molecular Medicine, The George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia, USA
| | - Eric S Nylen
- Division of Endocrinology, Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA.,Department of Biochemistry and Molecular Medicine, The George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia, USA
| | - Sabyasachi Sen
- Division of Endocrinology, Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA.,Department of Biochemistry and Molecular Medicine, The George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia, USA
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18
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Ji J, Wu L, Wei J, Wu J, Guo C. The Gut Microbiome and Ferroptosis in MAFLD. J Clin Transl Hepatol 2023; 11:174-187. [PMID: 36406312 PMCID: PMC9647110 DOI: 10.14218/jcth.2022.00136] [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: 03/21/2022] [Revised: 05/22/2022] [Accepted: 06/12/2022] [Indexed: 12/04/2022] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a new disease definition, and is proposed to replace the previous name, nonalcoholic fatty liver disease (NAFLD). Globally, MAFLD/NAFLD is the most common liver disease, with an incidence rate ranging from 6% to 35% in adult populations. The pathogenesis of MAFLD/NAFLD is closely related to insulin resistance (IR), and the genetic susceptibility to acquired metabolic stress-associated liver injury. Similarly, the gut microbiota in MAFLD/NAFLD is being revaluated by scientists, as the gut and liver influence each other via the gut-liver axis. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Emerging evidence suggests that ferroptosis has a key role in the pathological progression of MAFLD/NAFLD, and inhibition of ferroptosis may become a novel therapeutic strategy for the treatment of NAFLD. This review focuses on the main mechanisms behind the promotion of MAFLD/NAFLD occurrence and development by the intestinal microbiota and ferroptosis. It outlines new strategies to target the intestinal microbiota and ferroptosis to facilitate future MAFLD/NAFLD therapies.
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Affiliation(s)
- Jie Ji
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Liwei Wu
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jue Wei
- Department of Gastroenterology Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jianye Wu
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Correspondence to: Chuanyong Guo, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, NO. 301, Middle Yanchang Road, Jing’an District, Shanghai 200072, China. ORCID: https://orcid.org/0000-0002-6527-4673. E-mail: ; Jianye Wu: Department of Gastroenterology, Putuo People’s Hospital, NO. 1291, Jiangning road, Putuo, Shanghai 200060, China. ORCID: https://orcid.org/0000-0003-2675-4241. E-mail:
| | - Chuanyong Guo
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Correspondence to: Chuanyong Guo, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, NO. 301, Middle Yanchang Road, Jing’an District, Shanghai 200072, China. ORCID: https://orcid.org/0000-0002-6527-4673. E-mail: ; Jianye Wu: Department of Gastroenterology, Putuo People’s Hospital, NO. 1291, Jiangning road, Putuo, Shanghai 200060, China. ORCID: https://orcid.org/0000-0003-2675-4241. E-mail:
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Mohammadi M, Abbasalipourkabir R, Ziamajidi N. Fish oil and chicoric acid combination protects better against palmitate-induced lipid accumulation via regulating AMPK-mediated SREBP-1/FAS and PPARα/UCP2 pathways. Arch Physiol Biochem 2023; 129:1-9. [PMID: 32654534 DOI: 10.1080/13813455.2020.1789881] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with lipid accumulation and lipotoxicity. The main aim of this study is to evaluate the synergistic treatment effect of fish oils (FOs) and chicoric acid (CA) in palmitate (PA)-induced NAFLD HepG2 model. HepG2 cells were pre-treated with palmitate (0.75 mM) for 24 h, and then were exposed to CA, FOs and combination of these chemicals for another 24 h. Gene expression and protein levels were determined using qRT-PCR and western blotting or ELISA analysing, respectively. The combination index (CI) values of FOs and CA in HepG2 cells were calculated according to the Chou-Talalay equation using the CompuSyn software. FOs and CA acid together synergistically reduced lipid accumulation as indicated by decreased oil red O staining (vehicle-treated control: 1 ± 0.1; PA-treated control: 4.7 ± 0.4; PA + CA100: 3.9 ± 0.4; PA + CA200: 2.4 ± 0.3; PA + FOs: 2.7 ± 0.1; PA + CA200 + FOs: 1.5 ± 0.1) and triglyceride (vehicle-treatedcontrol:10 ± 1.2; PA-treated control: 25.8 ± 2.7; PA + CA100: 18.9 ± 2.5; PA + CA200: 14.4 ± 1.8; PA + FOs: 15.2 ± 2.4; PA + CA200 + FOs: 11.9 ± 1.5) levels in PA-treated HepG2 cells. Gene expression and Immunoblotting analysis confirmed the combination effect of FOs and CA in up-regulation of AMPK-mediated PPARα/UCP2 and down-regulation of AMPK-mediated SREBP-1/FAS signalling pathways. Collectively, these results suggest that combining FOs with CA can serve as a potential combination therapy for NAFLD.
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Affiliation(s)
- Mohammad Mohammadi
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Roghayeh Abbasalipourkabir
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Nasrin Ziamajidi
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
- Molecular Medicine Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
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20
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Tagkou NM, Goossens N. Stéatose hépatique non alcoolique : diagnostic et traitement en 2022. SCHWEIZER GASTROENTEROLOGIE 2023; 4:27-37. [PMCID: PMC9990575 DOI: 10.1007/s43472-023-00091-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/02/2023] [Indexed: 08/30/2023]
Abstract
La NAFLD (Non Alcoholic Fatty Liver Disease ) est la manifestation hépatique d’un trouble métabolique multisystémique. Elle est la principale cause de maladie hépatique au niveau mondial, avec une prévalence croissante. Bien qu’il s’agisse principalement d’une maladie silencieuse à évolution lente, certains patients présentent un risque élevé de progression de la maladie et d’issues plus graves telles que la cirrhose, le carcinome hépatocellulaire et la transplantation hépatique. Malgré les multiples études menées et les nombreux essais cliniques en cours, il n’existe pas de médicaments approuvés pour la NAFLD/NASH (Non Alcoholic Steato-Hepatitis ), et le traitement doit donc se fonder sur des stratégies de modification du mode de vie. Cette revue explorera la définition et l’épidémiologie courantes de la NAFLD et de la NASH ainsi que les facteurs de risque et les conséquences de la maladie, tout en résumant les recommandations existantes pour le diagnostic, la stratification du risque et la prise en charge de la maladie.
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Affiliation(s)
- Nikoletta Maria Tagkou
- Service de Gastroentérologie et d’Hépatologie, Hôpitaux Universitaires de Genève (HUG), Rue Gabrielle-Perret-Gentil 4, 1211 Genève 14, Suisse
| | - Nicolas Goossens
- Service de Gastroentérologie et d’Hépatologie, Hôpitaux Universitaires de Genève (HUG), Rue Gabrielle-Perret-Gentil 4, 1211 Genève 14, Suisse
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21
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Manouchehri S, Mirmohammadi SJ, Vakili M, Mehrparvar AH, Mirzaei M. Association between different patterns of shift work and liver function tests: A cross-sectional analysis of Shahedieh PERSIAN cohort data, Iran, 2020. Work 2023; 76:125-133. [PMID: 36744354 DOI: 10.3233/wor-220110] [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] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Recent studies suggest that shift work may cause liver dysfunction. OBJECTIVE This study aimed to examine the relationship between different patterns of shift work and elevated level of liver enzymes. METHODS In this cross-sectional study, 1910 workers aged 35 to 70 years were selected with simple random sampling from 9978 participants of the recruitment phase of Shahedieh PERSIAN cohort study. Level of serum liver enzymes (ALT, AST, ALP, and GGT) and ALT/AST ratio was compared between shift workers and non-shift workers, and among employees working in different patterns of shift work. Data were analyzed by SPSS (version 21.0) using Student's T test, Mann-Whitney U test, chi-square test, Kruskal Wallis test, and logistic regression. RESULTS Among 1347 males (71%) and 563 females (29%) with a mean age of 40.4±7.4 years, 469 were shift workers. Fixed evening type shift was the most common (30.3%) and fixed night-shift was the least common (0.9%) type of shift work. The mean blood levels of liver enzymes was not significantly different between shift workers and non-shift workers. In comparison between different patterns of shift work, the mean serum level of GGT was significantly higher in individuals with slow rotating shifts than those with fixed evening shifts, rapid rotating, split and fixed 24 hour shifts (p≤0.001). After adjusting for confounding factors only elevated AST was significantly higher in shift workers. CONCLUSION There was only a significant association between shift work and elevated AST, and no relationship was found with ALT, ALP, GGT, and ALT/AST ratio.
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Affiliation(s)
- Simin Manouchehri
- Department of Occupational Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | - Mahmood Vakili
- Health Monitoring Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | - Masoud Mirzaei
- Yazd Cardiovascular Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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22
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Diaconu CT, Guja C. Nonalcoholic Fatty Liver Disease and Its Complex Relation with Type 2 Diabetes Mellitus—From Prevalence to Diagnostic Approach and Treatment Strategies. J Clin Med 2022; 11:jcm11175144. [PMID: 36079070 PMCID: PMC9456683 DOI: 10.3390/jcm11175144] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 08/28/2022] [Accepted: 08/30/2022] [Indexed: 11/30/2022] Open
Abstract
Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Mellitus (T2DM) are increasing rapidly worldwide, reaching epidemic proportions. Their association, based on common metabolic risk factors (obesity, insulin resistance (IR), unhealthy lifestyle), brings an additional risk of both hepatic and cardiovascular (CV) adverse clinical outcomes. The terminology of “NAFLD” is stigmatizing to some but not all patients, and a more practical one should be announced soon. Medical strategies can address both diseases simultaneously, as they have crossing pathophysiological mechanisms, mainly IR. Strategies vary from lifestyle intervention and pharmacological options, as more molecules designated for T2DM treatment may be helpful in NAFLD, to surgical procedures. This review focuses on the coexistence of NAFLD and T2DM, pointing out the utility of the appropriate terminology, its prevalence, and mortality rates among the diabetic population. Briefly, we have discussed the main pathophysiological mechanisms and the risk stratification algorithm for the development of NAFLD and nonalcoholic steatohepatitis (NASH) as well as the tools for evaluation of fibrosis. Finally, we have focused on the current therapeutic options for the treatment of NAFLD associated with T2DM.
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Affiliation(s)
- Cosmina-Theodora Diaconu
- Department of Diabetes, Nutrition and Metabolic Diseases, “Prof. Dr. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 030167 Bucharest, Romania
- Doctoral School of “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu 37, 020021 Bucharest, Romania
- Correspondence:
| | - Cristian Guja
- Department of Diabetes, Nutrition and Metabolic Diseases, “Prof. Dr. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 030167 Bucharest, Romania
- Department of Diabetes, Nutrition and Metabolic Diseases, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
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23
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Zunica ERM, Heintz EC, Axelrod CL, Kirwan JP. Obesity Management in the Primary Prevention of Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14164051. [PMID: 36011044 PMCID: PMC9406638 DOI: 10.3390/cancers14164051] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/16/2022] [Accepted: 08/20/2022] [Indexed: 11/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and a leading cause of cancer-related death globally. HCC is associated with an indolent clinical presentation, resulting in frequent advanced stage diagnoses where surgical resection or transplant therapies are not an option and medical therapies are largely ineffective at improving survival. As such, there is a critical need to identify and enhance primary prevention strategies to mitigate HCC-related morbidity and mortality. Obesity is an independent risk factor for the onset and progression of HCC. Furthermore, obesity is a leading cause of nonalcoholic steatohepatitis (NASH), the fasting growing etiological factor of HCC. Herein, we review evolving clinical and mechanistic associations between obesity and hepatocarcinogenesis with an emphasis on the therapeutic efficacy of prevailing lifestyle/behavioral, medical, and surgical treatment strategies for weight reduction and NASH reversal.
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Affiliation(s)
| | | | | | - John P. Kirwan
- Correspondence: (C.L.A.); (J.P.K.); Tel.: +1-225-763-2513 (J.P.K.)
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24
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Lamboglia CG, Mccurdy AP, Kim YB, Lindeman C, Mangan AJ, Sivak A, Mager D, Spence JC. Investigation of movement-related behaviors and energy compensation in people living with liver disease: A scoping review. J Sports Sci 2022; 40:1299-1307. [PMID: 35766978 DOI: 10.1080/02640414.2022.2065087] [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] [Accepted: 03/31/2022] [Indexed: 10/17/2022]
Abstract
The importance of integrated movement behaviours (MB, i.e., physical activity [PA], sedentary behaviour, and sleep) and their interdependence for health has been recently discussed in the literature. The proposition that the amount of time spent in any one of these behaviours may impact the amount of time spent in another is supported by the ActivityStat hypothesis. The aim of this review is to (1) to assess whether individuals with liver disease display MB and/or energy (i.e., total energy expenditure [EE], basal EE, resting EE, and activity EE) compensation throughout the day and/or days; and (2) to examine whether a prescribed PA intervention triggers compensatory responses. Documents were included if they focused on people living with liver disease; analysed MB and/or EE components; were data-based; and were published in English. Fifteen documents were included in the final synthesis. The one finding that addressed research question 1 showed no compensatory response. As for research question 2, most of the findings suggest no compensation effects in response to a PA intervention. There is insufficient evidence to support the ActivityStat hypothesis in people living with liver disease. Further research should be conducted to test this hypothesis using standardized methodological procedures.
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Affiliation(s)
| | - Ashley P Mccurdy
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Yeong-Bae Kim
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Cliff Lindeman
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Amie J Mangan
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Allison Sivak
- H.T. Coutts Library, University of Alberta, Edmonton, Alberta, Canada
| | - Diana Mager
- Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - John C Spence
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
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25
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Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO). Eat Weight Disord 2022; 27:1603-1619. [PMID: 34914079 PMCID: PMC9123074 DOI: 10.1007/s40519-021-01287-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the past years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato, the Società Italiana di Diabetologia and the Società Italiana dell'Obesità reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure and Istituto Superiore di Sanità. Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources.Level of evidence Level of evidence of recommendations for each PICO question were reported according to available evidence.
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26
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Li J, Huang L, Xiong W, Qian Y, Song M. Aerobic exercise improves non-alcoholic fatty liver disease by down-regulating the protein expression of the CNPY2-PERK pathway. Biochem Biophys Res Commun 2022; 603:35-40. [DOI: 10.1016/j.bbrc.2022.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/20/2022] [Accepted: 03/01/2022] [Indexed: 11/02/2022]
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27
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Fernández T, Viñuela M, Vidal C, Barrera F. Lifestyle changes in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. PLoS One 2022; 17:e0263931. [PMID: 35176096 PMCID: PMC8853532 DOI: 10.1371/journal.pone.0263931] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 01/30/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease is a liver condition that is increasing worldwide and expected to become the number one cause of cirrhosis and hepatocellular carcinoma in the next 5 years. Currently there are no successful or approved pharmacological treatments. Weight loss is the first-line therapy as a 7 to 10% reduction improves steatosis, inflammation, hepatocyte ballooning, and fibrosis. To achieve this, lifestyle interventions including daily exercise and diet must be encouraged. We aimed to assess the effects of diet, exercise, or a combination of both compared to conventional treatment in patients with non-alcoholic fatty liver disease. METHODS AND FINDING A literature search was performed in CENTRAL, EMBASE, and PubMed. Randomized controlled trials comparing lifestyle changes with conventional treatment were included, without date restriction. Two authors searched studies according to eligibility criteria, extracted data, and assessed study quality. Subgroup analysis was made by type of intervention, duration of intervention and supervision. We calculated mean differences between the intervention and the control group with their corresponding 95% confidence intervals. Quality of the evidence was assessed using the Cochrane Risk of bias tool. This study is registered in PROSPERO, number CRD42020184241, and checked with the PRISMA checklist. 30 RCTs met the inclusion criteria. Compared to conventional treatment, combined exercise with diet seems to elicit greater reductions in ALT (MD: -13.27 CI 95% -21.39, -5.16), AST (MD: -7.02 CI 95% -11.26, -2.78) and HOMA-IR (MD: -2.07 CI 95% -2.61, -1.46) than diet (ALT MD: -4.48 CI 95% -1.01, -0.21; HOMA-IR MD: -0.61 CI 95% -1.01, -0.21) and exercise (ALT and AST non-significant; HOMA-IR MD = -0.46 CI 95% -0.8, -0.12) alone. Additionally, exercise improved quality of life, cardiorespiratory fitness, and weight (MD: -2.64 CI 95% -5.18, -0.09). CONCLUSION Lifestyle changes are effective in the treatment of NAFLD. Diet and exercise combined are superior to these interventions alone in improving liver enzymes and HOMA-IR.
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Affiliation(s)
- Tiziana Fernández
- Departamento Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Macarena Viñuela
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Catalina Vidal
- Departamento de Ortopedia y Traumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Barrera
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
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Objectively Measured Physical Activity Is Inversely Associated With Nonalcoholic Fatty Liver Disease: The Rotterdam Study. Am J Gastroenterol 2022; 117:311-318. [PMID: 34904966 PMCID: PMC8812433 DOI: 10.14309/ajg.0000000000001584] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 10/27/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The disease burden of nonalcoholic fatty liver disease (NAFLD) increases rapidly, in line with the obesity pandemic. Physical activity has been linked to a lower risk of NAFLD. However, the impact of different intensities of activity and sedentary behavior and whether their effects on NAFLD are explained by metabolic health remain unclear. METHODS We performed cross-sectional analyses within the population-based Rotterdam Study cohort. Abdominal ultrasound and accelerometry data were collected between 2009 and 2014. NAFLD was defined as hepatic steatosis diagnosed by ultrasound, in the absence of secondary causes for steatosis: viral hepatitis, steatogenic drugs, and excessive alcohol. We categorized accelerometry data into sedentary time and light, moderate, and vigorous physical activities. RESULTS We included 667 participants (aged 63.3 ± 6.3 years, 53% female individuals), and 34.3% had NAFLD. Total physical activity was associated with lower NAFLD prevalence adjusted for demographic, lifestyle, and socioeconomic factors (odds ratio: 0.958 per 10 min/d, 95% confidence interval [CI]: 0.929-0.986). More intensive physical activity was more strongly associated with lower NAFLD prevalence: odds ratios for light, moderate, and vigorous physical activities were 0.931 (95% CI: 0.882-0.982), 0.891 (95% CI: 0.820-0.967), and 0.740 (95% CI: 0.600-0.906) per 10 min/d, respectively. These associations were explained by metabolic health, particularly homeostatic model assessment of insulin resistance (proportion mediated: 0.59, P < 0.001) and waist circumference (proportion mediated: 1.08, P < 0.001). Beyond this indirect effect, no direct effect could be demonstrated (P = 0.282-0.827). DISCUSSION Physical activity at each intensity is inversely associated with NAFLD prevalence, with larger effects for higher intensities of physical activity. This association is mediated by better metabolic health, mainly lower insulin resistance and waist circumference. Physical activity should therefore be incorporated into NAFLD disease management and prevention programs.
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Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO). Dig Liver Dis 2022; 54:170-182. [PMID: 34924319 DOI: 10.1016/j.dld.2021.04.029] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 03/22/2021] [Accepted: 04/21/2021] [Indexed: 12/11/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.
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Marchesini G, Bugianesi E, Burra P, Marra F, Miele L, Alisi A, Vajro P, Masarone M, Petta S, Persico M, Svegliati-Baroni G, Valenti L, Federici M, Purrello F, Sasso FC, Targher G, Busetto L, Petroni ML, Santini F, Cammà C, Colli A. Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO). Nutr Metab Cardiovasc Dis 2022; 32:1-16. [PMID: 34924246 DOI: 10.1016/j.numecd.2021.04.028] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.
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A personalized treatment program in persons with type 2 diabetes is associated with a reduction in liver steatosis. Eur J Gastroenterol Hepatol 2021; 33:1420-1426. [PMID: 32796353 DOI: 10.1097/meg.0000000000001882] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS It is unclear if improving glycemic control in persons with type 2 diabetes (T2D) also has liver-related effects. We aimed to evaluate if a personalized treatment program associates with improvement of liver-related parameters in persons with advanced T2D in a real-life setting. METHODS Persons with advanced T2D underwent a 4-day personalized treatment program, with the aim of improving glycemic control by dietary advice, instructions on how to achieve optimal glucose control and individualized dosage of medications. Transient elastography was used to estimate liver steatosis and fibrosis. Persons with liver diseases other than non-alcoholic fatty liver disease (NAFLD) were excluded. After 3 months, study participants were offered re-examination. RESULTS Ninety-one persons were included. Of these, 75 persons (82%) had controlled attenuation parameter (CAP) measurements of acceptable quality at baseline. Of these, 57 (76%) had NAFLD (defined as >268 dB/m). Twenty-two persons (24%) had elevated liver stiffness (>7.9 kPa), and eight (9%) had liver stiffness above 13.9 kPa, indicating advanced fibrosis. Over a median follow-up of 101 days, mean CAP in persons with NAFLD was reduced by 18.33 dB/m (P = 0.035). In persons with elevated liver stiffness, mean stiffness was reduced by 2.6 kPa (P = 0.047). In linear regression, one-unit improvement in fasting glucose (mg/dl) was associated with a decrease in hepatic steatosis with 0.48 dB/m (adjusted R2 = 0.35, P < 0.01). CONCLUSION The prevalence of NAFLD with advanced fibrosis is high in persons with advanced T2D. Improving glycemic control through a personalized treatment program is associated with a reduction in liver steatosis and stiffness in this cohort.
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Deng YY, Zhong QW, Zhong HL, Xiong F, Ke YB, Chen YM. Higher Healthy Lifestyle Score is associated with lower presence of non-alcoholic fatty liver disease in middle-aged and older Chinese adults: a community-based cross-sectional study. Public Health Nutr 2021; 24:5081-5089. [PMID: 33634772 PMCID: PMC11082827 DOI: 10.1017/s1368980021000902] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 02/04/2021] [Accepted: 02/23/2021] [Indexed: 01/21/2023]
Abstract
OBJECTIVE Previous studies have reported inverse associations between certain healthy lifestyle factors and non-alcoholic fatty liver disease (NAFLD), but limited evidence showed the synergistic effect of those lifestyles. This study examined the relationship of a combination of lifestyles, expressed as Healthy Lifestyle Score (HLS), with NAFLD. DESIGN A community-based cross-sectional study. Questionnaires and body assessments were used to collect data on the six-item HLS (ranging from 0 to 6, where higher scores indicate better health). The HLS consists of non-smoking (no active or passive smoking), normal BMI (18·5-23·9 kg/m2), physical activity (moderate or vigorous physical activity ≥ 150 min/week), healthy diet pattern, good sleep (no insomnia or <6 months) and no anxiety (Self-rating Anxiety Scale < 50), one point each. NAFLD was diagnosed by ultrasonography. SETTING Guangzhou, China. PARTICIPANTS Two thousand nine hundred and eighty-one participants aged 40-75 years. RESULTS The overall prevalence of NAFLD was 50·8 %. After adjusting for potential covariates, HLS was associated with lower presence of NAFLD. The OR of NAFLD for subjects with higher HLS (3, 4, 5-6 v. 0-1 points) were 0·68 (95 % CI 0·51, 0·91), 0·58 (95 % CI 0·43, 0·78) and 0·35 (95 % CI 0·25, 0·51), respectively (P-values < 0·05). Among the six items, BMI and physical activity were the strongest contributors. Sensitivity analyses showed that the association was more significant after weighting the HLS. The beneficial association remained after excluding any one of the six components or replacing BMI with waist circumference. CONCLUSIONS Higher HLS was associated with lower presence of NAFLD, suggesting that a healthy lifestyle pattern might be beneficial to liver health.
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Affiliation(s)
- Yun-yang Deng
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou510080, People’s Republic of China
| | - Qing-wei Zhong
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou510080, People’s Republic of China
| | - Hai-li Zhong
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou510080, People’s Republic of China
| | - Feng Xiong
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou510080, People’s Republic of China
| | - Yue-bin Ke
- Key Laboratory of Molecular Epidemiology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, People’s Republic of China
| | - Yu-ming Chen
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou510080, People’s Republic of China
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Babu AF, Csader S, Lok J, Gómez-Gallego C, Hanhineva K, El-Nezami H, Schwab U. Positive Effects of Exercise Intervention without Weight Loss and Dietary Changes in NAFLD-Related Clinical Parameters: A Systematic Review and Meta-Analysis. Nutrients 2021; 13:nu13093135. [PMID: 34579012 PMCID: PMC8466505 DOI: 10.3390/nu13093135] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/05/2021] [Accepted: 09/05/2021] [Indexed: 12/13/2022] Open
Abstract
One of the focuses of non-alcoholic fatty liver disease (NAFLD) treatment is exercise. Randomized controlled trials investigating the effects of exercise without dietary changes on NAFLD-related clinical parameters (liver parameters, lipid metabolism, glucose metabolism, gut microbiota, and metabolites) were screened using the PubMed, Scopus, Web of Science, and Cochrane databases on 13 February 2020. Meta-analyses were performed on 10 studies with 316 individuals who had NAFLD across three exercise regimens: aerobic exercise, resistance training, and a combination of both. No studies investigating the role of gut microbiota and exercise in NAFLD were found. A quality assessment via the (RoB)2 tool was conducted and potential publication bias, statistical outliers, and influential cases were identified. Overall, exercise without significant weight loss significantly reduced the intrahepatic lipid (IHL) content (SMD: −0.76, 95% CI: −1.04, −0.48) and concentrations of alanine aminotransaminase (ALT) (SMD: −0.52, 95% CI: −0.90, −0.14), aspartate aminotransaminase (AST) (SMD: −0.68, 95% CI: −1.21, −0.15), low-density lipoprotein cholesterol (SMD: −0.34, 95% CI: −0.66, −0.02), and triglycerides (TG) (SMD: −0.59, 95% CI: −1.16, −0.02). The concentrations of high-density lipoprotein cholesterol, total cholesterol (TC), fasting glucose, fasting insulin, and glycated hemoglobin were non-significantly altered. Aerobic exercise alone significantly reduced IHL, ALT, and AST; resistance training alone significantly reduced TC and TG; a combination of both exercise types significantly reduced IHL. To conclude, exercise overall likely had a beneficial effect on alleviating NAFLD without significant weight loss. The study was registered at PROSPERO: CRD42020221168 and funded by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 813781.
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Affiliation(s)
- Ambrin Farizah Babu
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; (A.F.B.); (S.C.); (J.L.); (C.G.-G.); (K.H.); (H.E.-N.)
- Afekta Technologies Ltd., Yliopistonranta 1L, 70211 Kuopio, Finland
| | - Susanne Csader
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; (A.F.B.); (S.C.); (J.L.); (C.G.-G.); (K.H.); (H.E.-N.)
| | - Johnson Lok
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; (A.F.B.); (S.C.); (J.L.); (C.G.-G.); (K.H.); (H.E.-N.)
| | - Carlos Gómez-Gallego
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; (A.F.B.); (S.C.); (J.L.); (C.G.-G.); (K.H.); (H.E.-N.)
| | - Kati Hanhineva
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; (A.F.B.); (S.C.); (J.L.); (C.G.-G.); (K.H.); (H.E.-N.)
- Afekta Technologies Ltd., Yliopistonranta 1L, 70211 Kuopio, Finland
- Department of Life Technologies, Food Chemistry and Food Development Unit, University of Turku, 20500 Turku, Finland
| | - Hani El-Nezami
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; (A.F.B.); (S.C.); (J.L.); (C.G.-G.); (K.H.); (H.E.-N.)
- School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong 999077, China
| | - Ursula Schwab
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; (A.F.B.); (S.C.); (J.L.); (C.G.-G.); (K.H.); (H.E.-N.)
- Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, 70210 Kuopio, Finland
- Correspondence: ; Tel.: +358-403552791
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Lopez-Pascual A, Trayhurn P, Martínez JA, González-Muniesa P. Oxygen in Metabolic Dysfunction and Its Therapeutic Relevance. Antioxid Redox Signal 2021; 35:642-687. [PMID: 34036800 DOI: 10.1089/ars.2019.7901] [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] [Indexed: 11/13/2022]
Abstract
Significance: In recent years, a number of studies have shown altered oxygen partial pressure at a tissue level in metabolic disorders, and some researchers have considered oxygen to be a (macro) nutrient. Oxygen availability may be compromised in obesity and several other metabolism-related pathological conditions, including sleep apnea-hypopnea syndrome, the metabolic syndrome (which is a set of conditions), type 2 diabetes, cardiovascular disease, and cancer. Recent Advances: Strategies designed to reduce adiposity and its accompanying disorders have been mainly centered on nutritional interventions and physical activity programs. However, novel therapies are needed since these approaches have not been sufficient to counteract the worldwide increasing rates of metabolic disorders. In this regard, intermittent hypoxia training and hyperoxia could be potential treatments through oxygen-related adaptations. Moreover, living at a high altitude may have a protective effect against the development of abnormal metabolic conditions. In addition, oxygen delivery systems may be of therapeutic value for supplying the tissue-specific oxygen requirements. Critical Issues: Precise in vivo methods to measure oxygenation are vital to disentangle some of the controversies related to this research area. Further, it is evident that there is a growing need for novel in vitro models to study the potential pathways involved in metabolic dysfunction to find appropriate therapeutic targets. Future Directions: Based on the existing evidence, it is suggested that oxygen availability has a key role in obesity and its related comorbidities. Oxygen should be considered in relation to potential therapeutic strategies in the treatment and prevention of metabolic disorders. Antioxid. Redox Signal. 35, 642-687.
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Affiliation(s)
- Amaya Lopez-Pascual
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.,Neuroendocrine Cell Biology, Lund University Diabetes Centre, Lund University, Malmö, Sweden
| | - Paul Trayhurn
- Obesity Biology Unit, University of Liverpool, Liverpool, United Kingdom.,Clore Laboratory, The University of Buckingham, Buckingham, United Kingdom
| | - J Alfredo Martínez
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.,IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.,CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, Madrid, Spain.,Precision Nutrition and Cardiometabolic Health, IMDEA Food, Madrid Institute for Advanced Studies, Madrid, Spain
| | - Pedro González-Muniesa
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.,IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.,CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, Madrid, Spain
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Buzzetti E, Linden A, Best LM, Madden AM, Roberts D, Chase TJG, Freeman SC, Cooper NJ, Sutton AJ, Fritche D, Milne EJ, Wright K, Pavlov CS, Davidson BR, Tsochatzis E, Gurusamy KS. Lifestyle modifications for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 6:CD013156. [PMID: 34114650 PMCID: PMC8193812 DOI: 10.1002/14651858.cd013156.pub2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The prevalence of nonalcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases the risks of liver cirrhosis, hepatocellular carcinoma, and requirement for liver transplantation. There is uncertainty surrounding the relative benefits and harms of various lifestyle interventions for people with NAFLD. OBJECTIVES To assess the comparative benefits and harms of different lifestyle interventions in the treatment of NAFLD through a network meta-analysis, and to generate rankings of the different lifestyle interventions according to their safety and efficacy. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) in people with NAFLD, whatever the method of diagnosis, age, and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We planned to perform a network meta-analysis with OpenBUGS using Bayesian methods and to calculate the differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios (RaRs) with 95% credible intervals (CrIs) based on an available-participant analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. However, the data were too sparse for the clinical outcomes. We therefore performed only direct comparisons (head-to-head comparisons) with OpenBUGS using Bayesian methods. MAIN RESULTS We included a total of 59 randomised clinical trials (3631 participants) in the review. All but two trials were at high risk of bias. A total of 33 different interventions, ranging from advice to supervised exercise and special diets, or a combination of these and no additional intervention were compared in these trials. The reference treatment was no active intervention. Twenty-eight trials (1942 participants) were included in one or more comparisons. The follow-up ranged from 1 month to 24 months. The remaining trials did not report any of the outcomes of interest for this review. The follow-up period in the trials that reported clinical outcomes was 2 months to 24 months. During this short follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. This is probably because of the very short follow-up periods. It takes a follow-up of 8 years to 28 years to detect differences in mortality between people with NAFLD and the general population. It is therefore unlikely that differences by clinical outcomes will be noted in trials with less than 5 years to 10 years of follow-up. In one trial, one participant developed an adverse event. There were no adverse events in any of the remaining participants in this trial, or in any of the remaining trials, which seemed to be directly related to the intervention. AUTHORS' CONCLUSIONS The evidence indicates considerable uncertainty about the effects of the lifestyle interventions compared with no additional intervention (to general public health advice) on any of the clinical outcomes after a short follow-up period of 2 months to 24 months in people with nonalcohol-related fatty liver disease. Accordingly, high-quality randomised clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (a study design in which multiple interventions are trialed within large longitudinal cohorts of participants to gain efficiencies and align trials more closely to standard clinical practice), comparing aerobic exercise and dietary advice versus standard of care (exercise and dietary advice received as part of national health promotion). The reason for the choice of aerobic exercise and dietary advice is the impact of these interventions on indirect outcomes which may translate to clinical benefit. The outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource use measures including costs of intervention and decreased healthcare use after a minimum follow-up of eight years, to find meaningful differences in the clinically important outcomes.
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Affiliation(s)
- Elena Buzzetti
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Lawrence Mj Best
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Angela M Madden
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Thomas J G Chase
- Department of General Surgery, Homerton University Hospital NHS Foundation Trust, London, UK
| | - Suzanne C Freeman
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Nicola J Cooper
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Alex J Sutton
- Department of Health Sciences, University of Leicester, Leicester, UK
| | | | | | - Kathy Wright
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Chavdar S Pavlov
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Kurinchi Selvan Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
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Maier S, Wieland A, Cree-Green M, Nadeau K, Sullivan S, Lanaspa MA, Johnson RJ, Jensen T. Lean NAFLD: an underrecognized and challenging disorder in medicine. Rev Endocr Metab Disord 2021; 22:351-366. [PMID: 33389543 PMCID: PMC8893229 DOI: 10.1007/s11154-020-09621-1] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/15/2020] [Indexed: 12/14/2022]
Abstract
Classically, Non-Alcoholic Fatty Liver Disease (NAFLD) has been thought to be driven by excessive weight gain and obesity. The overall greater awareness of this disorder has led to its recognition in patients with normal body mass index (BMI). Ongoing research has helped to better understand potential causes of Lean NAFLD, the risks for more advanced disease, and potential therapies. Here we review the recent literature on prevalence, risk factors, severity of disease, and potential therapeutic interventions.
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Affiliation(s)
- Sheila Maier
- Division of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Amanda Wieland
- Division of Hepatology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Melanie Cree-Green
- Division of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Kristen Nadeau
- Division of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Shelby Sullivan
- Division of Gastroenterology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Miguel A Lanaspa
- Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA
| | - Richard J Johnson
- Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA
| | - Thomas Jensen
- Division of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
- Division of Endocrinology, University of Colorado, Denver, Denver, CO, USA.
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Imamura Y, Mawatari S, Oda K, Kumagai K, Hiramine Y, Saishoji A, Kakihara A, Nakahara M, Oku M, Hosoyamada K, Kanmura S, Moriuchi A, Miyahara H, Akio Ido. Changes in body composition and low blood urea nitrogen level related to an increase in the prevalence of fatty liver over 20 years: A cross-sectional study. Hepatol Res 2021; 51:570-579. [PMID: 33675676 DOI: 10.1111/hepr.13631] [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: 12/16/2020] [Revised: 02/13/2021] [Accepted: 02/28/2021] [Indexed: 02/08/2023]
Abstract
AIM Qualitative body composition (BC) change, characterized by the combination of visceral fat gain and muscle loss, is drawing attention as a risk factor for fatty liver (FL). The present study aimed to describe trends in BC change and its association with FL in the Japanese population. METHODS Data from medical checkups carried out on 56 639 Japanese participants every 5 years from 1997 to 2017 were analyzed. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated using body mass index and body fat percentage. Subjects were divided into two groups according to deviations from the correlation line of FMI and FFMI as the reference: FMI-predominant BC and FFM-dominant BC. Fatty liver was determined using abdominal ultrasonography. RESULTS The prevalence of FL significantly increased from 27.3% to 42.7% in men and from 18.0% to 25.5% in women. The prevalence of FMI predominance significantly increased from 33.6% to 43.9% in men and from 29.1% to 47.0% in women. Fat mass index predominance was independently associated with FL in men and women (odds ratio: 1.96 and 1.94, respectively). Serum blood urea nitrogen level was inversely associated with FL in men and women (0.958 and 0.961, respectively) and significantly decreased from 15.8 to 14.9 mg/dl in men and from 15.1 to 14.0 mg/dl in women. CONCLUSIONS Increasing FMI-predominant BC and decreasing serum blood urea nitrogen level could account for the increase in the prevalence of FL over 20 years. We believe that these factors stem from current lifestyle habits in Japan.
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Affiliation(s)
- Yasushi Imamura
- Department of Hepatology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Seiichi Mawatari
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kohei Oda
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kotaro Kumagai
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yasunari Hiramine
- Department of Hepatology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Akiko Saishoji
- Department of Hepatology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Atsuko Kakihara
- Department of Hepatology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Mai Nakahara
- Department of Nephrology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Manei Oku
- Department of Nephrology, Kajikionsen Hospital, Aira, Japan
| | - Kaori Hosoyamada
- Department of Diabetes, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Shuji Kanmura
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Akihiro Moriuchi
- Department of Gastroenterology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan
| | - Hironori Miyahara
- Medical Health Care Center, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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Lamos EM, Kristan M, Siamashvili M, Davis SN. Effects of anti-diabetic treatments in type 2 diabetes and fatty liver disease. Expert Rev Clin Pharmacol 2021; 14:837-852. [PMID: 33882758 DOI: 10.1080/17512433.2021.1917374] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are significant non-communicable diseases that often affect individuals concurrently. In individuals with both T2DM and NAFLD, there is evidence that anti-diabetic therapies may demonstrate potential combined beneficial metabolic and reduced hepatic inflammatory effects.Areas covered: A PubMed and Google Scholar search was performed to find relevant literature. Included studies focused on individuals with T2DM and NAFLD receiving anti-diabetic treatments including bariatric surgery, insulin sensitizers, incretin mimetics, and SGLT2 inhibitors. Additional articles highlight investigational treatments.Expert opinion: In individuals with T2DM and NAFLD, 5-10% weight loss or bariatric surgery if unable to lose weight or maintain weight loss are appropriate. GLP-1 receptor agonists and SGLT2 inhibitors result in weight loss, appear safe and may provide beneficial hepatic outcomes. Whether their effects are related to favorable weight changes or intrinsic hepatic effects is unclear. Thiazolidinediones have advantageous anti-hyperglycemic and hepatic effects but individuals must be monitored for weight gain and edema. Metformin and DPP-4 inhibitor beneficial hepatic effects remain debated. There are opportunities to standardize markers and imaging of NAFLD. Studies powered to evaluate the possible cardiovascular benefits of anti-diabetic therapies in individuals with T2DM and NAFLD are needed.
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Affiliation(s)
- Elizabeth M Lamos
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Megan Kristan
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Maka Siamashvili
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA
| | - Stephen N Davis
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
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Campbell P, Symonds A, Barritt AS. Therapy for Nonalcoholic Fatty Liver Disease: Current Options and Future Directions. Clin Ther 2021; 43:500-517. [PMID: 33583577 DOI: 10.1016/j.clinthera.2021.01.021] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/26/2021] [Accepted: 01/26/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that is driven by the metabolic syndrome. NAFLD encompasses nonalcoholic fatty liver, >5% fat in the liver without inflammation of fibrosis, nonalcoholic steatohepatitis (NASH), fat plus varying degrees of inflammation and fibrosis, and cirrhosis of the liver from NASH. As facets of the metabolic syndrome, particularly diabetes and obesity, become more common worldwide, the incidence of new NAFLD is increasing. METHODS A qualitative systematic review was performed via searches of PubMed and ClinicalTrials.gov for therapeutic interventions for NAFLD. FINDINGS Current therapies rely on metabolic syndrome risk factor control and lifestyle changes to achieve weight loss. Because sustained weight loss is difficult for many patients, there is a critical unmet need for pharmacotherapy to treat NAFLD, especially the progressive form, NASH, to prevent cirrhosis of the liver. New therapies for NAFLD focus on the subset of patients with NASH and some degree of fibrosis. Novel mechanisms of action, including farnesoid X nuclear receptor agonism, C-C motif chemokine receptor 2 and receptor 5 antagonism, stearoyl-CoA desaturase-1, and thyroid hormone receptor β agonism, are currently under investigation as monotherapy. The products also hold potential for use in combination with and without insulin sensitizers and other established drugs in the future. IMPLICATIONS This review of NASH treatments details the interventions that are currently available as well as those in late-stage clinical trials that may represent the future of NASH therapy.
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Affiliation(s)
- Patrick Campbell
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - Allison Symonds
- Department of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
| | - A Sidney Barritt
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
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O'Gorman P, Monaghan A, McGrath M, Naimimohasses S, Gormley J, Norris S. Determinants of Physical Activity Engagement in Patients With Nonalcoholic Fatty Liver Disease: The Need for an Individualized Approach to Lifestyle Interventions. Phys Ther 2021; 101:5940149. [PMID: 33104787 DOI: 10.1093/ptj/pzaa195] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 09/23/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Physical activity (PA) is an important non-pharmacological treatment for non-alcoholic fatty liver disease (NAFLD). This study investigated the determinants of PA engagement and awareness of the World Health Organization (WHO) PA guidelines in patients with NAFLD. METHODS Study participants were 101 patients with NAFLD (median age: 54 [IQR = 15] y; 53 men and 48 women) who completed 4 questionnaires: (1) a PA guideline awareness questionnaire; (2) a PA questionnaire assessing PA levels; and (3) 2 questionnaires assessing perceived barriers and motivators for engaging in PA. Binary logistic regression was performed to assess predictors of PA levels. RESULTS Twenty-four percent of participants correctly identified the recommended WHO weekly PA guidelines, and 39% adhered to the guidelines. Lack of willpower, time, and energy were the most frequently cited barrier domains. Scores for lack of willpower (odds ratio [OR] = 1.445, 95% CI = 1.088-1.919) and lack of resources (OR = 1.378, 95% CI = 1.003-1.893), and reporting 3 or more "significant" barrier domains (OR = 5.348, 95% CI = 1.792-15.873) were significant predictors of PA levels. Maintaining health and fitness was the most cited motivator domain and was a significant predictor (OR = 2.551, 95% CI = 1.253-5.208) of PA levels. CONCLUSIONS This study highlights the lack of awareness of the WHO PA guidelines and the key determinants of PA participation in patients with NAFLD. Determinants of PA should be identified at the individual level to create a personalized approach for PA maintenance for people with NAFLD to promote lifelong participation in PA. IMPACT This study closes a gap in the published data on the determinants of PA engagement in patients with NAFLD. LAY SUMMARY Physical inactivity is the fourth leading cause of global mortality and contributes to many chronic inflammatory diseases, including obesity, type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). People with NAFLD engage in less physical activity compared with people who are healthy, and this study provides new information that clinicians can use to help these patients increase their physical activity participation.
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Affiliation(s)
- Philip O'Gorman
- Discipline of Physiotherapy, University of Dublin, Trinity College, Dublin, Ireland
| | - Ann Monaghan
- Discipline of Physiotherapy, University of Dublin, Trinity College, Dublin, Ireland
| | - Marie McGrath
- Department of Hepatology, St James's Hospital, Dublin, Ireland
| | - Sara Naimimohasses
- Department of Hepatology, St James's Hospital, Dublin, Ireland.,Department of Clinical Medicine, University of Dublin, Trinity College, Dublin, Ireland
| | - John Gormley
- Discipline of Physiotherapy, University of Dublin, Trinity College, Dublin, Ireland
| | - Suzanne Norris
- Department of Hepatology, St James's Hospital, Dublin, Ireland.,Department of Clinical Medicine, University of Dublin, Trinity College, Dublin, Ireland
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Garcêz LS, Avelar CR, Fonseca NSS, Costa PRF, Lyra AC, Cunha CM, Jesus RP, Oliveira LPM. Effect of dietary carbohydrate and lipid modification on clinical and anthropometric parameters in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Nutr Rev 2021; 79:1321-1337. [PMID: 33515021 DOI: 10.1093/nutrit/nuaa146] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the adult population, making it one of the most common chronic liver diseases worldwide and a major public health problem. Still, there is no consensus on the most appropriate nutritional intervention for disease treatment. OBJECTIVE To systematize and synthesize the results of randomized controlled trials that have evaluated the effect of dietary interventions with different, quantitative, macronutrient compositions on hepatic steatosis attenuation, serum levels of alanine aminotransferase, aspartate aminotransferase, lipid profile, glucose metabolism markers, and anthropometric parameters of adults and the elderly (age ≥ 60 years) with NAFLD. DATA SOURCES MEDLINE databases via PubMed, Embase, Science Direct, LILACS, Web of Science, ClinicalTrials.gov, and Cochrane Library were searched. Randomized controlled trials that compared interventions as diets with values ≤ 45% or 20% of the total daily energy intake from carbohydrates or lipids, respectively, compared with dietary reference intakes, were included. DATA EXTRACTION Risk of bias was assessed through the Cochrane Collaboration tool. The meta-analysis was only performed to evaluate the effect of carbohydrate-modified diets on the outcome variables. The number of participants and mean values and respective standard deviations of the outcome variables were extracted and used to calculate weighted mean differences and their respective 95%CIs. RESULTS The search strategy resulted in 21 146 studies, of which 10 were retained for qualitative analysis and 6 were included in the meta-analysis. From the analysis of 10 studies were identified 8 articles in which low-calorie diets were evaluated and 3 interventions that used an isocaloric diet. Only 3 studies were classified as having low risk of bias. CONCLUSION The observed effects on hepatic steatosis, serum alanine aminotransferase and aspartate aminotransferase levels, parameters of lipid and glucose metabolism, and anthropometric variables were mostly related to a hypocaloric diet. The use of reduced macronutrient interventions had no efficacy. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42018088824.
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Affiliation(s)
- Lais S Garcêz
- Nutrition and Health Post-Graduation Programme, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Camila R Avelar
- Nutrition and Health Post-Graduation Programme, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Nedja S S Fonseca
- Science Nutrition Department, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Priscila R F Costa
- Nutrition and Health Post-Graduation Programme, Federal University of Bahia, Salvador, Bahia, Brazil
| | - André C Lyra
- Gastro-Hepatology Service, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Carla M Cunha
- Nutrition and Health Post-Graduation Programme, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Rosangela P Jesus
- Nutrition and Health Post-Graduation Programme, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Lucivalda P M Oliveira
- Nutrition and Health Post-Graduation Programme, Federal University of Bahia, Salvador, Bahia, Brazil
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Dokmak A, Lizaola-Mayo B, Trivedi HD. The Impact of Nonalcoholic Fatty Liver Disease in Primary Care: A Population Health Perspective. Am J Med 2021; 134:23-29. [PMID: 32931760 DOI: 10.1016/j.amjmed.2020.08.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 08/06/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, with rising rates in parallel to those of obesity, type 2 diabetes, and metabolic syndrome. NAFLD encompasses a wide spectrum of pathology from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis, which are linked to poor outcomes. Studies confirm a significant amount of undiagnosed NAFLD and related fibrosis within the community, increasing the overall burden of the disease. NAFLD appears to be more prevalent in certain populations, such as those with type 2 diabetes and metabolic syndrome. Early detection and lifestyle modifications, including weight loss and regular exercise, have been shown to improve outcomes. Adverse cardiovascular events are a key contributor to NAFLD-associated morbidity and mortality, and efforts to minimize their occurrence are essential. A targeted and algorithmic approach using noninvasive diagnostic techniques is promptly required to identify and risk-stratify patients with NAFLD. Patients at low risk of progression to NASH and advanced fibrosis can be managed in the primary care setting, while those at high risk of disease progression should be referred to hepatology specialists for surveillance and treatment. This review summarizes the key data of NAFLD's impact within primary care populations and proposes a potential algorithmic approach to identifying and managing such patients.
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Affiliation(s)
- Amr Dokmak
- Department of Hospital Medicine, Catholic Medical Center, Manchester, NH
| | - Blanca Lizaola-Mayo
- Division of Gastroenterology and Hepatology, Mayo Clinic in Arizona, Scottsdale
| | - Hirsh D Trivedi
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
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Machado MV. Aerobic Exercise in the Management of Metabolic Dysfunction Associated Fatty Liver Disease. Diabetes Metab Syndr Obes 2021; 14:3627-3645. [PMID: 34408459 PMCID: PMC8364841 DOI: 10.2147/dmso.s304357] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/29/2021] [Indexed: 12/17/2022] Open
Abstract
Sedentarism is the pandemic of modern times. It is associated with several medical conditions including obesity, type 2 diabetes mellitus, cardiovascular diseases and also liver disease, particularly metabolic dysfunction associated fatty liver disease (MAFLD). In an era when MAFLD is the most prevalent chronic liver disease worldwide, whilst no pharmacological therapy has been approved for it, exercise has proved to be effective in improving liver steatosis. Interestingly, exercise decreases liver fat even in the absence of weight loss. The challenge for the clinician is to motivate the obese patient with MAFLD, and associated co-morbidities, who has crystallized a sedentary behavior, at times when every need is at the distance of a click on the Internet, and the entire world can be visited behind a screen. In this review, the aggregate evidence on the mechanisms and effects of exercise in the management of MAFLD is summarized, with simple recommendations for everyday clinical practice.
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Affiliation(s)
- Mariana Verdelho Machado
- Serviço de Gastrenterologia, Hospital de Vila Franca de Xira, Vila Franca de Xira, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
- Correspondence: Mariana Verdelho Machado Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisboa, 1649-035, PortugalTel +35 1912620306 Email
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Raza S, Rajak S, Upadhyay A, Tewari A, Anthony Sinha R. Current treatment paradigms and emerging therapies for NAFLD/NASH. FRONT BIOSCI-LANDMRK 2021; 26:206-237. [PMID: 33049668 PMCID: PMC7116261 DOI: 10.2741/4892] [Citation(s) in RCA: 187] [Impact Index Per Article: 46.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one the fastest emerging manifestations of the metabolic syndrome worldwide. Non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, may culminate into cirrhosis and hepatocellular cancer (HCC) and is presently a leading cause of liver transplant. Although a steady progress is seen in understanding of the disease epidemiology, pathogenesis and identifying therapeutic targets, the slowest advancement is seen in the therapeutic field. Currently, there is no FDA approved therapy for this disease and appropriate therapeutic targets are urgently warranted. In this review we discuss the role of lifestyle intervention, pharmacological agents, surgical approaches, and gut microbiome, with regard to therapy for NASH. In particular, we focus the role of insulin sensitizers, thyroid hormone mimetics, antioxidants, cholesterol lowering drugs, incretins and cytokines as therapeutic targets for NASH. We highlight these targets aiming to optimize the future for NASH therapy.
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Affiliation(s)
- Sana Raza
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Sangam Rajak
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Aditya Upadhyay
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Archana Tewari
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Rohit Anthony Sinha
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India,
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Do A, Ilagan-Ying YC, Mehal WZ, Lim JK. Drug development of nonalcoholic fatty liver disease: challenges in research, regulatory pathways, and study endpoints. Expert Opin Drug Discov 2020; 16:125-134. [PMID: 33086894 DOI: 10.1080/17460441.2020.1811674] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION The growing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and its association with obesity as a metabolic disease contributes to harmful outcomes and healthcare resource burden worldwide. For this reason, there is an urgent need to develop new therapies. Identification of treatment targets, research design, endpoints definitions and assessments, and supportive regulatory pathways for drug approval all play prominent roles in shaping efforts in drug discovery, investigation, and approval. AREAS COVERED In this perspective, the authors enumerate key challenges of NAFLD clinical research and offer a conceptual framework to address these issues which arise during clinical trials. EXPERT OPINION With the anticipated significant healthcare and costs burden that NAFLD will impose throughout the world, the diagnostics and drug development processes need to be accelerated. Important measures to improve clinical trial research include standardization of case definitions, comprehensive and granular covariate data collection, quality study development incorporating novel trial designs, and quality data reporting. The authors believe that these actions will accelerate understanding, development, and ultimately approval of efficacious treatments.
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Affiliation(s)
- Albert Do
- Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine , New Haven, CT, USA
| | | | - Wajahat Z Mehal
- Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine , New Haven, CT, USA
| | - Joseph K Lim
- Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine , New Haven, CT, USA
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Abstract
The worldwide prevalence of non-alcoholic fatty liver disease is around 25%, and that of nonalcoholic steatohepatitis (NASH) ranges from 1.5% to 6.45%. Patients with NASH, especially those with fibrosis, are at higher risk for adverse outcomes such as cirrhosis and liver-related mortality. Although vitamin E, pioglitazone, and liraglutide improved liver histology in randomized trials, there are currently no Food and Drug Administration-approved drugs for NASH. Five pharmacologic agents-obeticholic acid, elafibranor, cenicriviroc, resmetirom, and aramchol-are being evaluated in large, histology-based phase 3 trials. Within 2 to 4 years, new and effective drugs for the treatment of NASH are expected. Additionally, many phase 2 trials are ongoing for various agents. Based on the results of phase 2 and 3 trials, combination treatments are also being investigated. Future treatment strategies will comprise drug combinations and precision medicine based on the different phenotypes of NASH and treatment response of the individual patient.
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Affiliation(s)
- Soung Won Jeong
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
- Corresponding author: Soung Won Jeong Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea E-mail:
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47
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Joo JH, Kim HJ, Park EC, Jang SI. Association between sitting time and non-alcoholic fatty live disease in South Korean population: a cross-sectional study. Lipids Health Dis 2020; 19:212. [PMID: 32967678 PMCID: PMC7513533 DOI: 10.1186/s12944-020-01385-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 09/06/2020] [Indexed: 12/13/2022] Open
Abstract
Background To examine the association between sitting time and non-alcoholic fatty liver disease among South Koreans aged ≥20 years. Methods Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for the analysis. Non-alcoholic fatty liver disease was diagnosed according to a hepatic steatosis index of > 36. Sitting time was categorized into as Q1, Q2, Q3, and Q4 using the age-adjusted quartile with Q4 being the longest sitting hour. Multiple logistic regression analysis was used to examine the association between sitting time and non-alcoholic fatty liver disease in South Korean population. Results A total of 13,518 participants were enrolled. The odds for having NAFLD in Q1, Q2, Q3, and Q4 (sitting hours) were 1.07 (CI: 0.88–1.31), 1.16 (CI: 1.96–1.41), and 1.34 (CI: 1.11–1.61), respectively. The odds ratio increased in magnitude with longer hours of sitting time (test for trend: P-value = 0.0002). Conclusion Advising physical exercises and discouraging sedentary activities may help to alleviate NAFLD among the South Korean population.
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Affiliation(s)
- Jae Hong Joo
- Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea.,Institute of Health Services Research, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Hwi Jun Kim
- Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea.,Institute of Health Services Research, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.,27th Infantry Division Medical Dispensary Operation Branch, Hwacheon, Republic of Korea
| | - Eun-Cheol Park
- Institute of Health Services Research, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.,Department of Preventive Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Sung-In Jang
- Institute of Health Services Research, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. .,Department of Preventive Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
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48
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Baek KW, Gim JA, Park JJ. Regular moderate aerobic exercise improves high-fat diet-induced nonalcoholic fatty liver disease via monoacylglycerol O-acyltransferase 1 pathway suppression. JOURNAL OF SPORT AND HEALTH SCIENCE 2020; 9:472-478. [PMID: 32928450 PMCID: PMC7498633 DOI: 10.1016/j.jshs.2018.09.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Revised: 03/16/2018] [Accepted: 04/26/2018] [Indexed: 06/11/2023]
Abstract
PURPOSE Monoacylglycerol O-acyltransferase 1 (MGAT1) is reported to play a key role in the development of diet-induced nonalcoholic fatty liver disease (NAFLD). Thus, this study investigated the effect of exercise on suppression of the MGAT1 pathway in NAFLD tissue of high-fat diet (HFD)-induced obese rats. METHODS Male Sprague-Dawley rats were fed an HFD containing 45% fat for 6 weeks. Upon confirmation that NAFLD had been induced in the obese animals, they were divided into HFD-fed groups provided with exercise (HFD + EXE) or without exercise (HFD) and a group given dietary adjustment (DA) only, for a further 6 weeks of intervention treatment. The 6-week regular moderate aerobic exercise consisted of an accommodation phase with increasing exercise. Lipid accumulation in the liver tissue was determined by Oil Red O staining. The MGAT1 and liver lipogenic gene mRNA levels were measured by qPCR, and their protein levels by western blot assay. RESULTS Oil Red O staining showed that NAFLD was successfully induced by HFD-fed. The gene expression of MGAT1 was significantly lower in HFD + EXE than HFD. However, there was no significant difference between HFD + EXE and DA. The protein expression of MGAT1 was significantly lower in HFD + EXE than both HFD and DA. Messenger RNA and protein expression of other lipogenic genes were not different among groups. These data indicate that exercise suppresses MGAT1 pathway regardless of HFD feeding; in part, this effect could be greater than DA. CONCLUSION Our data suggest that exercise can improve NAFLD, which is probably due to suppression of MGAT1 pathway.
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Affiliation(s)
- Kyung-Wan Baek
- Division of Sport Science, Pusan National University, Busan 46241, Korea
| | - Jeong-An Gim
- Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea
| | - Jung-Jun Park
- Division of Sport Science, Pusan National University, Busan 46241, Korea.
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Moon AM, Watkins SE, Lok AS, Firpi-Morell RJ, Trinh HN, Kupec JT, Schoen C, Neuschwander-Tetri BA, Barritt AS. Opioid Use Is More Common in Nonalcoholic Fatty Liver Disease Patients with Cirrhosis, Higher BMI, and Psychiatric Disease. Dig Dis 2020; 39:247-257. [PMID: 32836224 PMCID: PMC7902739 DOI: 10.1159/000511074] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 08/21/2020] [Indexed: 02/02/2023]
Abstract
BACKGROUND Opioid use is a topic of growing concern among patients with nonalcoholic fatty liver disease (NAFLD). Given safety concerns of opioids, proactively identifying subgroups of patients with an increased probability of opioid use may encourage practitioners to recommend alternative therapies for pain, thus reducing the likelihood of opioid misuse. This work assessed the prevalence and patient characteristics associated with opioid use in a real-world cohort of patients with NAFLD. METHODS TARGET-NASH, an observational study of participants at 55 academic and community sites in the United States, includes patients with NAFLD defined by pragmatic case definitions. Opioid use was defined as any documented opioid prescriptions in the year prior to enrollment. The association between patient characteristics and the odds of opioid use were modeled with stepwise multivariable logistic regression and tree ensemble methods (Classification and regression tree/Boosted Tree). RESULTS The cohort included 3,474 adult patients with NAFLD including 18.0% with documented opioid use. Variables associated with opioid use included presence of cirrhosis (OR 1.51, 95% CI 1.16-1.98), BMI ≥32 kg/m2 (OR 1.29, 95% CI 1.05-1.59), depression (OR 1.87, 95% CI 1.50-2.33), and anxiety (OR 1.59, 95% CI 1.27-1.98). In the boosted tree analysis, history of back pain, depression, and fibromyalgia had the greatest relative importance in predicting opioid use. CONCLUSION Prescription opioids were used in nearly 1 of 5 patients with NAFLD. Given the safety concerns of opioids in patients with NAFLD, alternative therapies including low-dose acetaminophen and nonpharmacologic treatments should be considered for these patients.
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Affiliation(s)
- Andrew M Moon
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, UNC Liver Center, Chapel Hill, North Carolina, USA,
| | | | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Roberto J Firpi-Morell
- Section of Hepatobiliary Diseases and Transplantation, University of Florida, Gainesville, Florida, USA
| | | | - Justin T Kupec
- Department of Medicine, Section of Digestive Diseases, West Virginia University, Morgantown, West Virginia, USA
| | - Cheryl Schoen
- TARGET PharmaSolutions, Inc., Durham, North Carolina, USA
| | | | - A Sidney Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, UNC Liver Center, Chapel Hill, North Carolina, USA
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Lim HS, Choi J, Lee B, Kim SG, Kim YS, Yoo JJ. Association between Inflammatory Biomarkers and Nutritional Status in Fatty Liver. Clin Nutr Res 2020; 9:182-194. [PMID: 32789148 PMCID: PMC7402975 DOI: 10.7762/cnr.2020.9.3.182] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 07/17/2020] [Accepted: 07/19/2020] [Indexed: 12/14/2022] Open
Abstract
The prevalence and progression of non-alcoholic fatty liver disease (NAFLD) is mediated via several factors correlating with hepatic necroinflammation (adipokines/cytokines). This study was performed to analyze the level of inflammatory markers according to the presence of NAFLD and to identify related nutritional factors. A total of 80 adults were classified into 2 groups (healthy and NAFLD), and their body composition, blood tests, and eating habits were evaluated. In addition, inflammatory markers (adiponectin, high-sensitivity C-reactive protein [CRP], and tumor necrosis factor-alpha [TNF-α]), nutrient intake status, and dietary quality were compared. The quality of diet was assessed according to the nutrient adequacy ratio and the mean adequacy ratio (MAR). The NAFLD group had a higher body mass index (p < 0.001) than the healthy group and also carried significantly higher CRP levels (p < 0.001) but lower adiponectin (p = 0.001). TNF-α levels increased significantly with fatty liver grade (p = 0.023). The NAFLD group showed significantly higher intake of energy, carbohydrates, iron, sodium, vitamin A and saturated fatty acids, but significantly lower intake of zinc and vitamin E than the healthy group. The MAR values were slightly higher in the NAFLD group but without any significant difference. The levels of adiponectin and vitamin E showed a significant inverse correlation (p < 0.05). Nutritional management of NAFLD patients is important, and the intake of antioxidant and anti-inflammatory nutrients such as zinc and vitamin E should be emphasized.
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Affiliation(s)
- Hee-Sook Lim
- Department of Food Sciences & Nutrition, Yeonsung University, Anyang 14011, Korea
| | - Joungyun Choi
- Department of Health and Nutrition Survey, Korean Centers for Disease Control & Prevention, Cheongju 28159, Korea
| | - Bora Lee
- Department of Biostatistics, Graduate School of Chung-Ang University, Seoul 06974, Korea
| | - Sang Gyune Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14854, Korea
| | - Young Seok Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14854, Korea
| | - Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14854, Korea
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