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Luthra R, Sheth A. Understanding MASH: An Examination of Progression and Clinical Outcomes by Disease Severity in the TARGET-NASH Database. Adv Ther 2025; 42:1165-1195. [PMID: 39739194 PMCID: PMC11787050 DOI: 10.1007/s12325-024-03085-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/04/2024] [Indexed: 01/02/2025]
Abstract
INTRODUCTION Metabolic dysfunction-associated steatohepatitis (MASH), the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), is linked to cardiometabolic risk factors such as obesity and type 2 diabetes (T2D). The rising prevalence of MASH and risk of hepatic and extra-hepatic complications emphasize the need for a better understanding of disease progression and associated outcomes. This study aimed to evaluate the incidence of, and demographic and clinical characteristics associated with, progression to MASH-related complications by disease severity in patients with non-cirrhotic MASH or MASH cirrhosis. Alignment between noninvasive tests (NITs) and biopsy-determined fibrosis stage was also assessed. METHODS This analysis used data from the TARGET-NASH cohort that includes adults with MASH across academic and community sites in the United States. Patients with non-cirrhotic MASH or MASH cirrhosis were stratified by disease severity based on fibrosis stage or cirrhosis. Progression to MASH-related outcomes, including all-cause mortality, cirrhosis, and liver transplantation, was assessed. RESULTS Among the 2378 patients included in this analysis, 48% had MASH cirrhosis. Incidence of all-cause mortality increased with disease severity from 0.14/100 person-months (100PM) at fibrosis stage 0-1 (F0-F1) to 2.02/100PM with compensated cirrhosis and 4.62/100PM with decompensated cirrhosis. Compared with patients with F0-F1, risk of progression to cirrhosis was higher in patients with F3 [hazard ratio (HR), 95% confidence interval (CI); 18.66, 10.97-31.73] and F2 (HR, 95% CI; 3.74, 2.00-6.98). Among those who progressed to MASH-related outcomes, 67.9% had T2D and 73.9% had hypertension. Vibration-controlled transient elastography showed better alignment with biopsy-determined fibrosis stage than Fibrosis-4 Index (FIB-4). CONCLUSIONS Progression to all-cause mortality in patients with MASH was significantly associated with the presence of higher fibrosis stage and cirrhosis. Cardiometabolic comorbidities such as T2D and hypertension were prevalent in patients with MASH progression. Early identification and management of MASH may mitigate disease progression and liver-related complications.
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Affiliation(s)
- Rakesh Luthra
- Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ, 08536, USA
| | - Aarth Sheth
- Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ, 08536, USA.
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Charlton M, Tonnu-Mihara I, Teng CC, Zhou Z, Asefaha F, Luthra R, Articolo A, Hoovler A, Uzoigwe C. Evaluating the burden of illness of metabolic dysfunction-associated steatohepatitis in a large managed care population: The ETHEREAL Study. J Manag Care Spec Pharm 2024; 30:1414-1430. [PMID: 39331041 PMCID: PMC11607210 DOI: 10.18553/jmcp.2024.24106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2024]
Abstract
BACKGROUND Metabolic dysfunction-associated steatohepatitis (MASH; formerly nonalcoholic steatohepatitis) is the inflammatory form of metabolic dysfunction-associated steatotic liver disease (formerly nonalcoholic fatty liver disease). MASH is a progressive disease associated with increased risk for many hepatic and extra-hepatic complications such as cirrhosis, hepatocellular carcinoma, the requirement for liver transplantation, and cardiovascular (CV)-related and kidney-related complications. It is important to understand the clinical and economic burden of MASH. OBJECTIVES To assess and compare the clinical and economic burdens of MASH in adults with the non-MASH population in a real-world setting. METHODS This observational, retrospective study used the Healthcare Integrated Research Database (HIRD), which contains health care claims data for commercially insured and Medicare Advantage health plan members across the United States. All-cause, CV-related, and liver-related medical costs and health care resource utilization were evaluated in patients with at least 2 diagnoses of MASH during the patient identification period (October 1, 2016, to April 30, 2022) and compared with a non-MASH cohort 1:1 matched on age, Quan Charlson Comorbidity Index, region of residence, and health plan type and length of enrollment. Generalized linear regression with negative binomial and γ distribution models were used to compare health care resource utilization and medical costs, respectively, while controlling for confounders. Covariate-adjusted all-cause, CV-related, and liver-related hospitalization rate ratios and medical cost ratios were assessed and compared for the MASH and matched non-MASH cohorts. RESULTS A total of 18,549 patients with MASH were compared with 18,549 matched patients in the non-MASH cohort. After adjusting for covariates, MASH was associated with significantly higher rates of hospitalization and higher medical costs compared with the non-MASH cohort. When compared with the non-MASH cohort, patients with MASH had 1.22 (95% CI = 1.15-1.30; P < 0.0001) times higher rates of all-cause hospitalization, 1.13 (95% CI = 1.03-1.24; P = 0.008) times higher rates of CV-related hospitalization, and 7.22 (95% CI = 4.91-10.61; P < 0.0001) times higher rates of liver-related hospitalization. Similarly, all-cause medical costs were 1.26 (95% CI = 1.22-1.30; P < 0.0001) times higher, CV-related medical costs were 1.66 (95% CI = 1.59-1.73; P < 0.0001) times higher, and liver-related medical costs were 7.79 (95% CI = 7.42-8.17; P < 0.0001) times higher among patients with MASH. CONCLUSIONS Compared with those of the non-MASH cohort with similar age, Quan Charlson Comorbidity Index, health plan, region of residence, and duration of enrollment, patients with MASH had significantly higher all-cause, CV-related, and liver-related hospitalizations and medical costs.
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Affiliation(s)
| | | | | | | | | | - Rakesh Luthra
- Health Economics and Outcomes Research, Novo Nordisk Inc., Plainsboro, NJ
| | - Amy Articolo
- Medical Affairs, Novo Nordisk Inc., Plainsboro, NJ
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Mucinski JM, Salvador AF, Moore MP, Fordham TM, Anderson JM, Shryack G, Cunningham RP, Lastra G, Gaballah AH, Diaz-Arias A, Ibdah JA, Rector RS, Parks EJ. Histological improvements following energy restriction and exercise: The role of insulin resistance in resolution of MASH. J Hepatol 2024; 81:781-793. [PMID: 38914313 PMCID: PMC12007730 DOI: 10.1016/j.jhep.2024.06.017] [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: 12/29/2023] [Revised: 05/29/2024] [Accepted: 06/04/2024] [Indexed: 06/26/2024]
Abstract
BACKGROUND & AIMS Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most common liver diseases worldwide and is characterized by multi-tissue insulin resistance. The effects of a 10-month energy restriction and exercise intervention on liver histology, anthropometrics, plasma biochemistries, and insulin sensitivity were compared to standard of care (control) to understand mechanisms that support liver health improvements. METHODS Following medical diagnosis of MASH, individuals were randomized to treatment (n = 16) or control (n = 8). Liver fat (magnetic resonance spectroscopy), 18-hour plasma biochemical measurements, and isotopically labeled hyperinsulinemic-euglycemic clamps were completed pre- and post-intervention. Body composition and cardiorespiratory fitness (VO2peak) were also measured mid-intervention. Those in the treatment group were counseled to reduce energy intake and completed supervised, high-intensity interval training (3x/week) for 10 months. Controls continued physician-directed care. RESULTS Treatment induced significant (p <0.05) reductions in body weight, fat mass, and liver injury, while VO2peak (p <0.05) and non-esterified fatty acid suppression (p = 0.06) were improved. Both groups exhibited reductions in total energy intake, hemoglobin A1c, hepatic insulin resistance, and liver fat (p <0.05). Compared to control, treatment induced a two-fold increase in peripheral insulin sensitivity which was significantly related to higher VO2peak and resolution of liver disease. CONCLUSIONS Exercise and energy restriction elicited significant and clinically meaningful treatment effects on liver health, potentially driven by a redistribution of excess nutrients to skeletal muscle, thereby reducing hepatic nutrient toxicity. Clinical guidelines should emphasize the addition of aerobic exercise in lifestyle treatments for the greatest histologic benefit in individuals with advanced MASH. IMPACT AND IMPLICATIONS The mechanisms that underpin histologic improvement in individuals with metabolic dysfunction-associated steatohepatitis (MASH) are not well understood. This study evaluated the relationship between liver and metabolic health, testing how changes in one may affect the other. We investigated the effects of energy restriction and exercise on the association between multi-tissue insulin sensitivity and histologic improvements in participants with biopsy-proven MASH. For the first time, these results show that an improvement in peripheral (but not hepatic) insulin sensitivity and systemic markers of muscle function (i.e. cardiorespiratory fitness) were strongly related to resolution of liver disease. Extrahepatic disposal of substrates and improved fitness levels supported histologic improvement, confirming the addition of exercise as crucial to lifestyle interventions in MASH. CLINICAL TRIAL NUMBER NCT03151798.
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Affiliation(s)
- Justine M Mucinski
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States
| | - Amadeo F Salvador
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States
| | - Mary P Moore
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States; Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO 65201, United States
| | - Talyia M Fordham
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States
| | - Jennifer M Anderson
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States
| | - Grace Shryack
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States; NextGen Precision Health, Columbia, MO 65201, United States
| | - Rory P Cunningham
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States; Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO 65201, United States
| | - Guido Lastra
- Endocrinology and Metabolism, School of Medicine, University of Missouri, Columbia, MO 65212, United States
| | - Ayman H Gaballah
- Department of Radiology, School of Medicine, University of Missouri, Columbia, MO, 65212, United States
| | - Alberto Diaz-Arias
- Boyce & Bynum Pathology Laboratories, Columbia, MO, 65201, United States
| | - Jamal A Ibdah
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States; Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO 65201, United States; Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine, University of Missouri, Columbia, MO 65212, United States; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, 65212, United States
| | - R Scott Rector
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States; Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO 65201, United States; NextGen Precision Health, Columbia, MO 65201, United States; Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine, University of Missouri, Columbia, MO 65212, United States
| | - Elizabeth J Parks
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, United States; NextGen Precision Health, Columbia, MO 65201, United States; Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine, University of Missouri, Columbia, MO 65212, United States.
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Mohamed I, Gautam M, Abosheaishaa H, Hussain S, Kumar K, Kotak A, Baugh M, Qureshi R, Jaber F, Dahiya DS, Alba L, Duong N. Growth hormone augmentation in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials. Eur J Gastroenterol Hepatol 2024; 36:1259-1266. [PMID: 38973533 DOI: 10.1097/meg.0000000000002819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis and metabolic dysregulation. Growth hormone (GH) augmentation has emerged as a potential therapeutic intervention for treating MASLD. This systematic review and meta-analysis aimed to evaluate the impact of GH augmentation on different parameters of MASLD. A systematic literature search identified randomized controlled trials investigating GH augmentation in MASLD patients. Search results were screened via Covidence and the Risk of Bias 2 tool was used to assess bias in randomized controlled trials. Statistical analysis utilized RevMan v5.3. We combined dichotomous outcomes employing odds ratios and continuous outcomes utilizing mean difference (MD), each with a 95% confidence interval (CI). Statistical significance was indicated by a P -value less than 0.05. Heterogeneity was evaluated using I2 tests. Our results showed that GH augmentation resulted in a significant reduction in both relative (MD: -46.26; 95% CI: -71.52, -21.00; P = 0.0003) and absolute (MD: -5.15; 95% CI: -7.93, -2.37; P = 0.0003) hepatic fat fraction. GH augmentation significantly reduced alanine aminotransferase (MD: -5.97; 95% CI: -10.31, -1.62; P = 0.007) and gamma-glutamyl transferase (MD: -16.18; 95% CI: -30.76, -1.59; P = 0.03) levels. No significant changes were observed in hemoglobin A1c, C-reactive protein, fasting serum glucose, BMI, triglycerides, and low-density lipoprotein cholesterol levels. Our meta-analysis highlights GH augmentation as a promising therapy for reducing liver steatosis and improving liver enzyme levels in MASLD patients. Further large-scale trials are warranted to examine the long-term effects, safety profiles, and potential impact on various measures.
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Affiliation(s)
- Islam Mohamed
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, Missouri
| | - Misha Gautam
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, Missouri
| | - Hazem Abosheaishaa
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Sophia Hussain
- School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri
| | - Kopal Kumar
- School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri
| | - Anaya Kotak
- School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri
| | - Macy Baugh
- School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri
| | - Raabia Qureshi
- School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri
| | - Fouad Jaber
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, Missouri
| | | | - Laura Alba
- Department of Gastroenterology and Hepatology, University of Missouri-Kansas City, Kansas City, Missouri
| | - Nikki Duong
- Department of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA
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Al Ghaithi F, Waly MI, Al-Farsi Y, Al Mukhaini Z, Al Balushi R, Almashrafi A. Biochemical and nutritional determinants of non-alcoholic fatty liver disease in Omani adult patients: a case-control study. INTERNATIONAL JOURNAL OF NUTRITION, PHARMACOLOGY, NEUROLOGICAL DISEASES 2024; 14:407-415. [DOI: 10.4103/ijnpnd.ijnpnd_57_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 08/05/2024] [Indexed: 01/03/2025]
Abstract
Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is a risk factor for atherosclerosis, diabetes, kidney disease, and liver cirrhosis. Limited research exists on the biochemical and nutritional elements influencing NAFLD among adult patients in Oman. Objective: This study aimed to characterize the biochemical parameters and nutritional factors of Omani adults diagnosed with NAFLD at the Diwan Polyclinic in Muscat, Oman. Methods: This retrospective case–control study included 104 participants (52 cases and 52 controls) who have 2 or more risk factors for NAFLD and were referred to the Radiology department from January 2021 to January 2022 for abdominal ultrasound after Internal Medicine consultations. A validated scale, incorporating a semi-quantitative food frequency questionnaire, was employed. Results: The study revealed a significantly higher risk of NAFLD among men (69%) compared to women (31%). A common characteristic among participants was a prior diabetes diagnosis, 61.5% of the case group and 65% of the control group. While average liver enzyme levels were within the normal range for both groups, alanine transaminase levels were notably elevated in the case group. The case group exhibited a significantly higher average caloric intake than the control group. Conclusion: NAFLD is significantly more common among men. Alanine transaminase is significantly high in NAFLD group, which might be considered as a biochemical marker for NAFLD, but further investigations are needed. Moreover, high daily caloric intake is directly related to NAFLD.
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Affiliation(s)
| | - Mostafa I. Waly
- Food Science and Nutrition Department, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman
| | - Yahya Al-Farsi
- Family Medicine and Public Health, College of Medicine and Health Sciences, Sultan Qaboos University, Oman
| | | | - Ruqaiya Al Balushi
- Food Science and Nutrition Department, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman
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Shakhshir M, Zyoud SH. Mapping global research trends: Nutrition associations with nonalcoholic fatty liver disease - a Scopus bibliometric analysis. World J Gastroenterol 2024; 30:3106-3119. [PMID: 38983957 PMCID: PMC11230064 DOI: 10.3748/wjg.v30.i24.3106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 05/10/2024] [Accepted: 06/05/2024] [Indexed: 06/25/2024] Open
Abstract
BACKGROUND Several bibliometric analyses have been carried out to identify research hotspots and trends in nonalcoholic fatty liver disease (NAFLD) research. Nonetheless, there are still significant knowledge gaps that must be filled to advance our understanding of and ability to treat NAFLD. AIM To evaluate, through bibliometric and visual analysis, the current status of related research, related research frontiers, and the developmental trends in the field of diet and NAFLD. METHODS We retrieved publications about diet and NAFLD published between 1987 and 2022 from Scopus. Next, we used VOSviewer 1.6.20 to perform bibliometric analysis and visualization. RESULTS We found a total of 1905 studies, including 1637 (85.93%) original articles and 195 (10.24%) reviews, focused on the examination of NAFLD and its correlation with diet that were published between 1987 and 2022. Among the remaining five types of documents, 38 were letters, notes, editorials, meeting minutes, or brief surveys, representing 1.99% of the total documents. The countries with the most publications on this topic were China (n = 539; 28.29%), followed by the United States (n = 379; 19.90%), Japan (n = 133; 6.98%), and South Korea (n = 127; 6.6%). According to the citation analysis, the retrieved papers were cited an average of 32.3 times and had an h-index of 106, with 61014 total citations. The two main clusters on the map included those related to: (1) Inflammation and oxidative stress; and (2) Dietary interventions for NAFLD. CONCLUSION This was the first study to use data taken from Scopus to visualize network mapping in a novel bibliometric analysis of studies focused on diet and NAFLD. After 2017, the two domains that received the most attention were "dietary interventions for NAFL"' and "'inflammation and oxidative stress implicated in NAFLD and its correlation with diet." We believe that this study provides important information for academics, dietitians, and doctors, and that additional research on dietary interventions and NAFLD is warranted.
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Affiliation(s)
- Muna Shakhshir
- Department of Nutrition, An-Najah National University Hospital, Nablus 44839, Palestine
- Department of Public Health, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
| | - Sa'ed H Zyoud
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Poison Control and Drug Information Center, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Clinical Research Center, An-Najah National University Hospital, Nablus 44839, Palestine
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Savari F, Mard SA. Nonalcoholic steatohepatitis: A comprehensive updated review of risk factors, symptoms, and treatment. Heliyon 2024; 10:e28468. [PMID: 38689985 PMCID: PMC11059522 DOI: 10.1016/j.heliyon.2024.e28468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 03/17/2024] [Accepted: 03/19/2024] [Indexed: 05/02/2024] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease and a progressive and chronic liver disorder with a significant risk for the development of liver-related morbidity and mortality. The complex and multifaceted pathophysiology of NASH makes its management challenging. Early identification of symptoms and management of patients through lifestyle modification is essential to prevent the development of advanced liver disease. Despite the increasing prevalence of NASH, there is no FDA-approved treatment for this disease. Currently, medications targeting metabolic disease risk factors and some antifibrotic medications are used for NASH patients but are not sufficiently effective. The beneficial effects of different drugs and phytochemicals represent new avenues for the development of safer and more effective treatments for NASH. In this review, different risk factors, clinical symptoms, diagnostic methods of NASH, and current treatment strategies for the management of patients with NASH are reviewed.
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Affiliation(s)
- Feryal Savari
- Department of Medical Basic Sciences, Shoushtar Faculty of Medical Sciences, Shoushtar, Iran
| | - Seyed Ali Mard
- Clinical Sciences Research Institute, Alimentary Tract Research Center, Department of Physiology, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Garousi N, Tamizifar B, Pourmasoumi M, Feizi A, Askari G, Clark CCT, Entezari MH. Effects of lacto-ovo-vegetarian diet vs. standard-weight-loss diet on obese and overweight adults with non-alcoholic fatty liver disease: a randomised clinical trial. Arch Physiol Biochem 2023; 129:975-983. [PMID: 33689525 DOI: 10.1080/13813455.2021.1890128] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 01/13/2021] [Accepted: 02/07/2021] [Indexed: 12/18/2022]
Abstract
The aim of the study was to compare the effects of a lacto-ovo-vegetarian diet (LOV-D) vs. a standard weight-loss diet (SWL-D) on obese/overweight adults with NAFLD. Present randomised clinical trial recruited 75 overweight/obese adults with NAFLD, who were randomly assigned into LOV-D and SWL-D groups for 3 months. The LOV-D was designed based on eliminating meat, poultry, and fish; while including dairy products and eggs. The SWL-D was planned according to the standard food pyramid, which was free in all sources of food. Adherence to LOV-D significantly outperformed SWL-D in reducing levels of alanine aminotransferase (ALT), body weight, waist circumference, BMI, fasting blood sugar, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triacylglycerol (TG), cholesterol, low-density lipoprotein cholesterol (LDL-C), and systolic blood pressure (SBP). Furthermore, ultrasonography revealed a higher alleviation in NAFLD grade among LOV-D, compared with SWL-D. This study suggests that adherence to LOV-D for 3 months has beneficial effects on NAFLD improvement, anthropometric measures, glycaemic-related markers, and lipid profiles.
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Affiliation(s)
- Nazila Garousi
- Department of Clinical Nutrition, Food Security and Nutrition Research Center, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Babak Tamizifar
- Gastroenterlogy and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Makan Pourmasoumi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Awat Feizi
- Department of Epidemiology and Biostatistics, School of Public Health, Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gholamreza Askari
- Department of Community Nutrition, Food Security and Nutrition Research Center, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Cain C T Clark
- Centre for Intelligent Healthcare, Coventry University, Coventry, UK
| | - Mohammad Hasan Entezari
- Department of Clinical Nutrition, Food Security and Nutrition Research Center, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Calin-Necula A, Enciu V, Ologeanu P, Moldoveanu AC, Braticevici CF. The correlation between Body Mass Index and histological features of Nonalcoholic Fatty Liver Disease. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2023; 61:147-153. [PMID: 37148286 DOI: 10.2478/rjim-2023-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Indexed: 05/08/2023]
Abstract
Introduction: NAFLD is strongly associated with metabolic syndrome, and for many years, fatty liver was an exclusive feature of obese patients. The study tries to assess whether the body mass index (BMI) and body circumference is correlated to steatosis, fibrosis, or inflammatory activity of the liver. Methods: 81 patients with recent hepatic biopsy were included in the study and were weighed and measured. The biopsy results were compared to the measurements. Results: The average BMI overall for the whole lot was 30.16. There was a significant difference in BMI across the inflammatory activity categories (p = 0.009): groups with higher necro inflammatory activity tended to have higher BMI values (average values per grade: 0-28, 1-29, 2-33, 3-32, 4-29). There was no significant difference for grades of steatosis (p = 0.871). With regards to waist circumference, the overall average was 90.70cm/35.70in. There was a significant difference across the steatosis categories (p < 0.001): groups with higher steatosis scores had higher waist circumferences (average values per grade: 1-77cm / 30 in, 2-95 cm / 37 in, 3-94 cm / 37 in). There was no significant difference for grades of activity (p = 0.058). Conclusion: BMI and waist circumference are easy to measure, non-invasive parameters, which could be useful in screening patients at higher risk for necro inflammatory activity or severe steatosis.
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Affiliation(s)
- Ana Calin-Necula
- 1Internal Medicine II and Gastroenterology Department, "Carol Davila" University of Medicine and Pharmacy Bucharest
- 2Emergency University Hospital Bucharest
| | - Vlad Enciu
- 1Internal Medicine II and Gastroenterology Department, "Carol Davila" University of Medicine and Pharmacy Bucharest
- 2Emergency University Hospital Bucharest
| | - Priscila Ologeanu
- 1Internal Medicine II and Gastroenterology Department, "Carol Davila" University of Medicine and Pharmacy Bucharest
- 2Emergency University Hospital Bucharest
| | - Alexandru Constantin Moldoveanu
- 1Internal Medicine II and Gastroenterology Department, "Carol Davila" University of Medicine and Pharmacy Bucharest
- 2Emergency University Hospital Bucharest
| | - Carmen Fierbinteanu Braticevici
- 1Internal Medicine II and Gastroenterology Department, "Carol Davila" University of Medicine and Pharmacy Bucharest
- 2Emergency University Hospital Bucharest
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Balakrishnan M, Liu K, Schmitt S, Heredia NI, Sisson A, Montealegre JR, Hernaez R, Kanwal F, Foreyt J. Behavioral weight-loss interventions for patients with NAFLD: A systematic scoping review. Hepatol Commun 2023; 7:e0224. [PMID: 37534947 PMCID: PMC10553168 DOI: 10.1097/hc9.0000000000000224] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 06/12/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Clinically significant weight loss-which requires sustained dietary and physical activity changes-is central to treating NAFLD. Although behavioral interventions have demonstrated effectiveness in promoting weight loss among primary prevention populations, the data are limited among patients with NAFLD who need weight loss for treatment. We undertook this scoping review to map the existing data on the characteristics, weight-loss outcomes, and determinants of success of interventions evaluated among patients with NAFLD. METHODS We searched Medline, EMBASE, Cochrane, PsycINFO, and Web of Science from inception to January 1, 2023 to identify publications reporting weight loss among adults with NAFLD in behavioral weight-loss interventions. We summarized interventions and classified them as successful if there was an average weight loss of ≥ 5% from baseline across enrolled participants or achieved by ≥ 50% of enrolled participants. RESULTS We included 28 studies: 10 randomized control trials, ten quasi-experimental, and 8 observational studies. Intervention delivery, duration, and counseling frequency varied; 12 were successful. Retention was highest among telephone interventions and lowest among "real-world" face-to-face interventions. Patients who were women, younger, and/or had multiple metabolic conditions were most likely to dropout. Successful interventions had biweekly counseling, specific physical activity, and calorie targets, behavioral theory grounding, and promoted goal-setting, self-monitoring, and problem-solving. CONCLUSION There are limited data on behavioral weight-loss interventions in NAFLD. Research is needed to develop effective interventions generalizable to diverse patient populations and that maximize adherence, particularly among patients who are diabetic, women, and younger.
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Affiliation(s)
- Maya Balakrishnan
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Kyle Liu
- Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Sydney Schmitt
- Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Natalia I. Heredia
- Department of Health Promotion & Behavioral Sciences, The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas, USA
| | - Amy Sisson
- Houston Academy of Medicine Texas Medical Center Library, Houston, Texas, USA
| | | | - Ruben Hernaez
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - John Foreyt
- Division of General Internal Medicine, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
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11
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Vallée A. Arterial stiffness and biological parameters: A decision tree machine learning application in hypertensive participants. PLoS One 2023; 18:e0288298. [PMID: 37418473 DOI: 10.1371/journal.pone.0288298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 06/23/2023] [Indexed: 07/09/2023] Open
Abstract
Arterial stiffness, measured by arterial stiffness index (ASI), could be considered a main denominator in target organ damage among hypertensive subjects. Currently, no reported ASI normal references have been reported. The index of arterial stiffness is evaluated by calculation of a stiffness index. Predicted ASI can be estimated regardless to age, sex, mean blood pressure, and heart rate, to compose an individual stiffness index [(measured ASI-predicted ASI)/predicted ASI]. A stiffness index greater than zero defines arterial stiffness. Thus, the purpose of this study was 1) to determine determinants of stiffness index 2) to perform threshold values to discriminate stiffness index and then 3) to determine hierarchical associations of the determinants by performing a decision tree model among hypertensive participants without CV diseases. A study was conducted from 53,363 healthy participants in the UK Biobank survey to determine predicted ASI. Stiffness index was applied on 49,452 hypertensives without CV diseases to discriminate determinants of positive stiffness index (N = 22,453) from negative index (N = 26,999). The input variables for the models were clinical and biological parameters. The independent classifiers were ranked from the most sensitives: HDL cholesterol≤1.425 mmol/L, smoking pack years≥9.2pack-years, Phosphate≥1.172 mmol/L, to the most specifics: Cystatin c≤0.901 mg/L, Triglycerides≥1.487 mmol/L, Urate≥291.9 μmol/L, ALT≥22.13 U/L, AST≤32.5 U/L, Albumin≤45.92 g/L, Testosterone≥5.181 nmol/L. A decision tree model was performed to determine rules to highlight the different hierarchization and interactions between these classifiers with a higher performance than multiple logistic regression (p<0.001). The stiffness index could be an integrator of CV risk factors and participate in future CV risk management evaluations for preventive strategies. Decision trees can provide accurate and useful classification for clinicians.
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Affiliation(s)
- Alexandre Vallée
- Department of Epidemiology and Public Health, Foch hospital, Suresnes, France
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12
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Mátis D, Hegyi P, Teutsch B, Tornai T, Erőss B, Pár G, Váncsa S. Improved body composition decreases the fat content in non-alcoholic fatty liver disease, a meta-analysis and systematic review of longitudinal studies. Front Med (Lausanne) 2023; 10:1114836. [PMID: 37215704 PMCID: PMC10194653 DOI: 10.3389/fmed.2023.1114836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 04/13/2023] [Indexed: 05/24/2023] Open
Abstract
Background Based on cross-sectional studies, there is a link between body composition parameters and steatosis in non-alcoholic fatty liver disease (NAFLD). However, whether long-term changes in different body composition parameters will result in NAFLD resolution is unclear. Therefore, we aimed to summarize the literature on longitudinal studies evaluating the association between NAFLD resolution and body composition change. Methods Based on the recommendations of the Cochrane Handbook, we performed a systematic search on September 26th, 2021, in three databases: Embase, MEDLINE (via PubMed), and Cochrane Central Register of Controlled Trials (CENTRAL). Eligible studies reported on patients with NAFLD (liver fat >5%) and examined the correlation between body composition improvement and decrease in steatosis. We did not have pre-defined body composition or steatosis measurement criteria. Next, we calculated pooled correlation coefficient (r) with a 95% confidence interval (CI). Furthermore, we narratively summarized articles with other statistical methods. Results We included 15 studies in our narrative review and five in our quantitative synthesis. Based on two studies with 85 patients, we found a pooled correlation coefficient of r = 0.49 (CI: 0.22-0.69, Spearman's correlation) between the change of visceral adipose tissue and liver steatosis. Similarly, based on three studies with 175 patients, the correlation was r = 0.33 (CI: 0.19-0.46, Pearson's correlation). On the other hand, based on two studies with 163 patients, the correlation between subcutaneous adipose tissue change and liver steatosis change was r = 0.42 (CI: 0.29-0.54, Pearson's correlation). Furthermore, based on the studies in the narrative synthesis, body composition improvement was associated with steatosis resolution. Conclusions Based on the included studies, body composition improvement may be associated with a decrease in liver fat content in NAFLD. Systematic review registration Identifier: CRD42021278584.
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Affiliation(s)
- Dóra Mátis
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Brigitta Teutsch
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Tamás Tornai
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Bálint Erőss
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Gabriella Pár
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Szilárd Váncsa
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
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13
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Effects of a Dulaglutide plus Calorie-Restricted Diet versus a Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial. Nutrients 2023; 15:nu15030556. [PMID: 36771262 PMCID: PMC9920202 DOI: 10.3390/nu15030556] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/09/2023] [Accepted: 01/18/2023] [Indexed: 01/24/2023] Open
Abstract
The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (-0.97 cm2, 95% confidence interval from -14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.
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14
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Seifi N, Bahari H, Soltani S, Nikoumanesh M, Hajipoor M, Ferns GA, Ghayour-Mobarhan M. The effects of electronic-based lifestyle interventions on nonalcoholic fatty liver disease: A systematic review. Digit Health 2023; 9:20552076231187597. [PMID: 37529544 PMCID: PMC10388623 DOI: 10.1177/20552076231187597] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 06/23/2023] [Indexed: 08/03/2023] Open
Abstract
OBJECTIVE Lifestyle interventions are increasingly becoming an integrated part of nonalcoholic fatty liver disease (NAFLD) management. Electronic lifestyle interventions may be able to expand the access and utility of this approach. This study aimed to synthesize the evidence for the effects of electronic-based lifestyle interventions on weight, anthropometric, and liver enzyme measurements in patients with NAFLD. METHODS Medline, Scopus, and Web of Science were searched up to February 2023. Clinical trials investigating the effects of electronic lifestyle interventions on weight, body mass index (BMI), waist circumference (WC), and liver enzymes in NAFLD patients were reviewed. After reviewing full-text articles, seven clinical trials were included in the systematic review. RESULTS Two articles included telephone calls, one was based on text messaging, two studies were based on web-based lifestyle modifications, and two used mobile apps. Except for one, all other six studies indicated a significant impact on weight loss. BMI was reported in six of seven studies. Except for one, BMI was significantly reduced in the group receiving e-health. WC was reported in four studies, which indicated a significant reduction in the e-health intervention group. Alanine transaminase (ALT) was reported in all the included studies. Except for two, others demonstrated a significant improvement in ALT in the e-health intervention groups. As reported in four studies, Aspartate transaminase (AST) significantly decreased in the group receiving e-health interventions, except in one study. CONCLUSIONS The results support applying electronic lifestyle interventions in NAFLD patients to reduce weight, BMI, WC, AST, and ALT.
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Affiliation(s)
- Najmeh Seifi
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Bahari
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sanaz Soltani
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahya Nikoumanesh
- Department of Nutrition Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
| | - Mojtaba Hajipoor
- Department of Nutrition Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
| | - Gordon A. Ferns
- Department of Medical Education, Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, UK
| | - Majid Ghayour-Mobarhan
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
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15
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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16
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Authors, Collaborators:. Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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17
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Sato S, Kamata Y, Kessoku T, Shimizu T, Kobayashi T, Kurihashi T, Takashiba S, Hatanaka K, Hamada N, Kodama T, Higurashi T, Taguri M, Yoneda M, Usuda H, Wada K, Nakajima A, Morozumi T, Minabe M. A cross-sectional study assessing the relationship between non-alcoholic fatty liver disease and periodontal disease. Sci Rep 2022; 12:13621. [PMID: 35948584 PMCID: PMC9365789 DOI: 10.1038/s41598-022-17917-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 08/02/2022] [Indexed: 11/09/2022] Open
Abstract
The risk factors for non-alcoholic fatty liver disease (NAFLD) progression are not completely known. Porphyromonas gingivalis infection is a risk factor for systemic diseases. We investigated the association of P. gingivalis infection with the risk of non-alcoholic steatohepatitis progression. Here, hematological tests, periodontal examination, and saliva collection were performed for 164 patients with NAFLD. P. gingivalis was identified in saliva using polymerase chain reaction. Hepatic steatosis and stiffness were evaluated using vibration-controlled transient elastography (VCTE) and magnetic resonance imaging. In patients with NAFLD, P. gingivalis positivity (P. gingivalis ratio ≥ 0.01%) in saliva correlated with liver stiffness determined using magnetic resonance elastography (MRE; p < 0.0001). A P. gingivalis ratio of 0.01% corresponds to 100,000 cells/mL and indicates the proportion of P. gingivalis in the total number of bacteria in the oral cavity. Patients with NAFLD and advanced fibrosis on MRE showed significantly elevated endotoxin activity; those who had > 10 periodontal pockets with depths ≥ 4 mm had significantly increased hepatic stiffness on both VCTE and MRE.
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Affiliation(s)
- Satsuki Sato
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Yohei Kamata
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan.
| | - Takaomi Kessoku
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Tomoko Shimizu
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Takeo Kurihashi
- Department of Internal Medicine, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Shogo Takashiba
- Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan
| | - Kazu Hatanaka
- Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan
| | - Nobushiro Hamada
- Division of Microbiology, Department of Oral Science Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Toshiro Kodama
- Department of Implantology and Periodontology, Graduate School of Dentistry, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Takuma Higurashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Masataka Taguri
- Department of Biostatistics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Haruki Usuda
- Department of Pharmacology, Shimane University School of Medicine, 89-1 Enya-cho Izumo, Shimane, 693-0581, Japan
| | - Koichiro Wada
- Department of Pharmacology, Shimane University School of Medicine, 89-1 Enya-cho Izumo, Shimane, 693-0581, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Toshiya Morozumi
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Masato Minabe
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
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Sayegh NF, Heraoui GNHA, Younes H, Sayegh LN, Boulos C, Sayegh R. Relation of Dietary Patterns and Nutritional Profile to Hepatic Fibrosis in a Sample of Lebanese Non-Alcoholic Fatty Liver Disease Patients. Nutrients 2022; 14:nu14122554. [PMID: 35745284 PMCID: PMC9229197 DOI: 10.3390/nu14122554] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/15/2022] [Accepted: 06/17/2022] [Indexed: 11/16/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver injury worldwide. NAFLD can evolve into non-alcoholic steatohepatitis (NASH) with or without fibrosis. The objectives of this study were to determine the nutritional profile and dietary patterns of NAFLD Lebanese patients and to report the type of diet-related to the presence of hepatic fibrosis. We hypothesized that the traditional pattern was related to a low risk of fibrosis. This cross-sectional study included 320 eligible Lebanese NAFLD patients. Three dietary patterns were identified: the Traditional diet, the High Fruit diet, and the Westernized diet. Multivariate analysis showed a significant relationship between high adherence to the traditional diet and absence of hepatic fibrosis with a decreased risk of 82%, p = 0.031 after adjusting for its covariables. Fruits were absent from this dietary pattern. Although our results pointed to a possible relationship between fibrosis in NAFLD patients and fruit intake, experimental studies are needed to show whether this is a causal relationship. However, the results obtained in this study may contribute to the planning of dietary interventions and recommendations and enable a better follow-up for NAFLD patients with fibrosis.
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Affiliation(s)
- Nicole Fakhoury Sayegh
- Department of Nutrition, Faculty of Pharmacy, Saint Joseph University, Damascus Road, Riad el Solh, Beirut P.O. Box 11-5076, Lebanon; (G.N.H.A.H.); (C.B.)
- Correspondence: or
| | - Gessica N. H. A. Heraoui
- Department of Nutrition, Faculty of Pharmacy, Saint Joseph University, Damascus Road, Riad el Solh, Beirut P.O. Box 11-5076, Lebanon; (G.N.H.A.H.); (C.B.)
| | - Hassan Younes
- College Health, équipe PANASH-ULR 7519, Institut Polytechnique UniLaSalle, 19, Rue Pierre Waguet, CEDEX, 60026 Beauvais, France;
| | - Lea Nicole Sayegh
- Faculty of Medicine, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon;
| | - Christa Boulos
- Department of Nutrition, Faculty of Pharmacy, Saint Joseph University, Damascus Road, Riad el Solh, Beirut P.O. Box 11-5076, Lebanon; (G.N.H.A.H.); (C.B.)
| | - Raymond Sayegh
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saint Joseph University, Damascus Road, Riad el Solh, Beirut P.O. Box 11-5076, Lebanon;
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19
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Asghari S, Rezaei M, Rafraf M, Taghizadeh M, Asghari-Jafarabadi M, Ebadi M. Effects of Calorie Restricted Diet on Oxidative/Antioxidative Status Biomarkers and Serum Fibroblast Growth Factor 21 Levels in Nonalcoholic Fatty Liver Disease Patients: A Randomized, Controlled Clinical Trial. Nutrients 2022; 14:nu14122509. [PMID: 35745238 PMCID: PMC9231395 DOI: 10.3390/nu14122509] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/11/2022] [Accepted: 06/13/2022] [Indexed: 02/01/2023] Open
Abstract
Oxidative stress plays a fundamental role in the development and progression of nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of a calorie-restricted (CR) diet on oxidative/anti-oxidative status in patients with NAFLD and the potential mediating role of fibroblast growth factor 21 (FGF-21) in this regard. This randomized, controlled clinical trial was carried out on sixty patients with NAFLD aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m2. Participants were randomly assigned to either the CR diet group (received a prescribed low-calorie diet for twelve weeks, n = 30) or the control group (n = 30). Fasting blood samples, anthropometric measurements, dietary intake, and physical activity data were collected for all participants at baseline and at the end of the trial. Significant reductions in weight, BMI, waist circumference, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed in the CR diet group compared to the control group (all p < 0.05). Liver steatosis grade, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and FGF-21, as well as erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities did not show significant changes in the CR group when compared to the controls at the end of the study (p > 0.05). CR diet with moderate weight loss has some favorable effects on NAFLD but was not able to modify oxidative/anti-oxidative status in these patients. Future studies are warranted to target the effects of long-term interventions with a greater weight loss in this patient population.
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Affiliation(s)
- Somayyeh Asghari
- Department of Clinical Nutrition, Faculty of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 141556117, Iran; (S.A.); (M.R.); (M.T.)
| | - Mahsa Rezaei
- Department of Clinical Nutrition, Faculty of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 141556117, Iran; (S.A.); (M.R.); (M.T.)
| | - Maryam Rafraf
- Nutrition Research Center, Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz 5166614711, Iran;
| | - Mahdiyeh Taghizadeh
- Department of Clinical Nutrition, Faculty of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 141556117, Iran; (S.A.); (M.R.); (M.T.)
| | - Mohammad Asghari-Jafarabadi
- Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz 5166614711, Iran;
- Cabrini Research, Cabrini Health, 154 Wattletree Rd, Malvern, VIC 3144, Australia
| | - Maryam Ebadi
- Division of Gastroenterology & Liver Unit, University of Alberta, Edmonton, AB T6G 2X8, Canada
- Correspondence: ; Tel.: +1-780-248-1892
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20
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Rojano-Toimil A, Rivera-Esteban J, Manzano-Nuñez R, Bañares J, Martinez Selva D, Gabriel-Medina P, Ferrer R, Pericàs JM, Ciudin A. When Sugar Reaches the Liver: Phenotypes of Patients with Diabetes and NAFLD. J Clin Med 2022; 11:jcm11123286. [PMID: 35743358 PMCID: PMC9225139 DOI: 10.3390/jcm11123286] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/03/2022] [Accepted: 06/06/2022] [Indexed: 01/27/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) have been traditionally linked to one another. Recent studies suggest that NAFLD may be increasingly common in other types of diabetes such as type 1 diabetes (T1DM) and less frequently ketone-prone and Maturity-onset Diabetes of the Young (MODY) diabetes. In this review, we address the relationship between hyperglycemia and insulin resistance and the onset and progression of NAFLD. In addition, despite the high rate of patients with T2DM and other diabetes phenotypes that can alter liver metabolism and consequently develop steatosis, fibrosis, and cirrhosis, NALFD screening is not still implemented in the daily care routine. Incorporating a clinical algorithm created around a simple, non-invasive, cost-effective model would identify high-risk patients. The principle behind managing these patients is to improve insulin resistance and hyperglycemia states with lifestyle changes, weight loss, and new drug therapies.
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Affiliation(s)
- Alba Rojano-Toimil
- Endocrinology Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain;
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
| | - Jesús Rivera-Esteban
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Medicine Department Bellaterra, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
| | - Ramiro Manzano-Nuñez
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
| | - Juan Bañares
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
| | - David Martinez Selva
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Spanish Network of Biomedical Research Centers, Diabetes and Metabolic Associated Disorders (CIBERdem), 28029 Madrid, Spain
| | - Pablo Gabriel-Medina
- Biochemistry Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain; (P.G.-M.); (R.F.)
- Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona (UAB), Bellaterra, 08193 Barcelona, Spain
| | - Roser Ferrer
- Biochemistry Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain; (P.G.-M.); (R.F.)
| | - Juan M Pericàs
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Spanish Network of Biomedical Research Centers, Liver and Digestive Diseases (CIBERehd), 28801 Madrid, Spain
- Correspondence: (J.M.P.); (A.C.)
| | - Andreea Ciudin
- Endocrinology Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain;
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Medicine Department Bellaterra, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
- Spanish Network of Biomedical Research Centers, Diabetes and Metabolic Associated Disorders (CIBERdem), 28029 Madrid, Spain
- Correspondence: (J.M.P.); (A.C.)
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21
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Glass L, Asefa H, Volk M, Lok AS, Tincopa MA. Disease Knowledge, Health-Related Quality of Life, and Lifestyle Behavior Change in Patients with Nonalcoholic Fatty Liver Disease: Impact of an Educational Intervention. Dig Dis Sci 2022; 67:2123-2133. [PMID: 34043121 DOI: 10.1007/s10620-021-07052-9] [Citation(s) in RCA: 15] [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] [Received: 03/02/2021] [Accepted: 05/11/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND Lifestyle modification is currently the only treatment for nonalcoholic fatty liver disease (NAFLD). The most effective way to motivate behavior change in this population is not well understood. AIMS The aims of this study were to characterize the association between patient disease knowledge, attitudes, and behaviors and to determine the impact of an educational intervention. METHODS Adults with NAFLD had the following assessed before and after an educational intervention: (1) disease knowledge; (2) health-related quality of life (HRQOL); (3) physical activity; (4) diet; (5) stages of change; and (6) clinical variables. RESULTS Median age of the cohort (N = 248) was 53.5, 46% were male, 85% were white, and median body mass index was 33.9. Forty-eight percentage had nonalcoholic steatohepatitis, and 28% had cirrhosis. The median correct knowledge score was 73.6%, median Chronic Liver Disease Questionnaire-NAFLD was 5.2/7, and diet score was 7/16 (higher indicating unhealthy diets). The cohort was sedentary at baseline, with 46% and 60% in active phases of change for nutrition and physical activity, respectively. Fifty-six (22%) had all three high-risk behaviors (sedentary, poor diet scores, low stage of change), which was independently associated with depression. The educational intervention improved diet scores, HRQOL, stages of change, and weight. CONCLUSIONS Despite good disease knowledge, NAFLD participants were sedentary and 1/4 had high-risk lifestyle behaviors. An educational intervention had positive impacts on clinical outcomes, though effect size was small. Pairing educational interventions with targeted interventions to motivate behavior change can improve care for patients with NAFLD.
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Affiliation(s)
- Lisa Glass
- Department of Internal Medicine, John D. Dingell VA Medical Center, Detroit, MI, USA
| | - Haila Asefa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, 1500 East Medical Center Drive, SPC 5362, Ann Arbor, MI, 48109, USA
| | - Michael Volk
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, 1500 East Medical Center Drive, SPC 5362, Ann Arbor, MI, 48109, USA
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22
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Liu J, Shi Y, Peng D, Wang L, Yu N, Wang G, Chen W. Salvia miltiorrhiza Bge. (Danshen) in the Treating Non-alcoholic Fatty Liver Disease Based on the Regulator of Metabolic Targets. Front Cardiovasc Med 2022; 9:842980. [PMID: 35528835 PMCID: PMC9072665 DOI: 10.3389/fcvm.2022.842980] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 03/28/2022] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is rapidly prevalent due to its strong association with increased metabolic syndrome such as cardio- and cerebrovascular disorders and diabetes. Few drugs can meet the growing disease burden of NAFLD. Salvia miltiorrhiza Bge. (Danshen) have been used for over 2,000 years in clinical trials to treat NAFLD and metabolic syndrome disease without clarified defined mechanisms. Metabolic targets restored metabolic homeostasis in patients with NAFLD and improved steatosis by reducing the delivery of metabolic substrates to liver as a promising way. Here we systematic review evidence showing that Danshen against NAFLD through diverse and crossing mechanisms based on metabolic targets. A synopsis of the phytochemistry and pharmacokinetic of Danshen and the mechanisms of metabolic targets regulating the progression of NAFLD is initially provided, followed by the pharmacological activity of Danshen in the management NAFLD. And then, the possible mechanisms of Danshen in the management of NAFLD based on metabolic targets are elucidated. Specifically, the metabolic targets c-Jun N-terminal kinases (JNK), sterol regulatory element-binding protein-1c (SREBP-1c), nuclear translocation carbohydrate response element–binding protein (ChREBP) related with lipid metabolism pathway, and peroxisome proliferator-activated receptors (PPARs), cytochrome P450 (CYP) and the others associated with pleiotropic metabolism will be discussed. Finally, providing a critical assessment of the preclinic and clinic model and the molecular mechanism in NAFLD.
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Affiliation(s)
- Jie Liu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology, Hefei, China
| | - Yun Shi
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Daiyin Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Lei Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology, Hefei, China
- *Correspondence: Lei Wang,
| | - Nianjun Yu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Guokai Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Weidong Chen
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology, Hefei, China
- Weidong Chen,
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23
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Arora C, Malhotra A, Ranjan P, Singh V, Singh N, Shalimar, Dwivedi SN, Vikram NK. Effect of intensive weight-loss intervention on metabolic, ultrasound and anthropometric parameters among patients with obesity and non-alcoholic fatty liver disease: an RCT. Eur J Clin Nutr 2022; 76:1332-1338. [PMID: 35444271 PMCID: PMC9020151 DOI: 10.1038/s41430-022-01111-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 02/04/2022] [Accepted: 02/22/2022] [Indexed: 11/18/2022]
Abstract
Background Lifestyle intervention is the mainstay therapy for Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to assess the efficacy of an intensive (9 contact points in 6 months) weight-loss intervention among patients with obesity (BMI 25–39.9 kg/m2) and NAFLD in north India. Methods A total of 140 patients (18–60 years) with obesity and NAFLD were randomized into intervention (n = 70) and control (n = 70) groups, at a tertiary-care hospital. Weight, anthropometric parameters, Controlled Attenuation Parameter (CAP), Liver Stiffness Measurement (LSM), liver enzymes, grade of fatty liver and HOMA-IR were measured at baseline (T0) and 6 months (T6). There was a high drop-out, exacerbated by the Covid-19 pandemic. Completers comprised of 59 participants (n = 30 intervention, n = 29 control). Intention to treat analysis was done. Results At T6, ALT normalized in significantly higher (p = 0.03) number of cases in the intervention arm (66.7%) versus control arm (18.2%). No significant improvement was seen in other metabolic, ultrasound or anthropometric outcomes. Weight (p < 0.001), AST (p = 0.01), ALT (p = 0.02), body fat% (p < 0.001), WC (p < 0.001) and CAP (p < 0.001) significantly improved within the intervention arm along with a trend of improvement in steatosis and HOMA-IR. Control group showed significant decrease in weight (p < 0.001), WC (p < 0.001) and CAP (p = 0.02). Twice the number of patients in intervention arm (46.7%) lost ≥5% weight, compared to control arm (24.1%) (p = 0.07). Conclusion The intensive weight-loss intervention was not effective in improving the treatment outcomes among patients with obesity and NAFLD. However, given the potential of our intervention, we recommend larger trials with more intensive weight-loss interventions.
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Affiliation(s)
- Charu Arora
- Department of Home Science, University of Delhi, Delhi, India
| | - Anita Malhotra
- Department of Home Science, Lakshmibai College, University of Delhi, Delhi, India
| | - Piyush Ranjan
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
| | - Vishwajeet Singh
- Dept. of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Namrata Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - S N Dwivedi
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Naval K Vikram
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
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24
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Nah EH, Cho S, Park H, Noh D, Kwon E, Cho HI. Subclinical steatohepatitis and advanced liver fibrosis in health examinees with nonalcoholic fatty liver disease (NAFLD) in 10 South Korean cities: A retrospective cross-sectional study. PLoS One 2021; 16:e0260477. [PMID: 34818372 PMCID: PMC8612540 DOI: 10.1371/journal.pone.0260477] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 11/10/2021] [Indexed: 01/17/2023] Open
Abstract
Background Nonalcoholic steatohepatitis (NASH) has a risk of progressing to cirrhosis. The prevalence of NASH and its associated risk factors in community populations are relatively unknown. This study aimed to determine the prevalence of NASH and advanced liver fibrosis using magnetic resonance elastography (MRE), and determine those risk factors in health examinees with asymptomatic fatty liver. Methods This study consecutively selected subjects who underwent health checkups at 13 health-promotion centers in 10 Korean cities between 2018 and 2020. Hepatic steatosis and stiffness were assessed using ultrasonography and MRE, respectively. Stages of liver stiffness were estimated using MRE with cutoff values for NASH and advanced liver fibrosis of 2.91 and 3.60 kPa, respectively. Results The overall prevalence of NASH and advanced liver fibrosis in the subjects with fatty liver were 8.35% and 2.04%, respectively. Multivariate logistic regression analysis indicated that central obesity (OR = 5.12, 95% CI = 2.70–9.71), increased triglyceride (OR = 3.29, 95% CI = 1.72–6.29), abnormal liver function test (OR = 3.09, 95% CI = 1.66–5.76) (all P<0.001), and decreased high-density lipoprotein cholesterol (OR = 5.18, 95% CI = 1.78–15.05) (P = 0.003) were associated with NASH. The main risk factor for advanced liver fibrosis was diabetes (OR = 4.46, 95% CI = 1.14–17.48) (P = 0.032). Conclusion NASH or advanced liver fibrosis is found in one-tenth of health examinees with asymptomatic fatty liver. This suggests that early detection of NASH should be considered to allow early interventions such as lifestyle changes to prevent the adverse effects of NASH and its progression in health examinees with asymptomatic fatty liver.
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Affiliation(s)
- Eun-Hee Nah
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Seon Cho
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Hyeran Park
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Dongwon Noh
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Eunjoo Kwon
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Han-Ik Cho
- MEDIcheck LAB, Korea Association of Health Promotion, Seoul, Korea
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25
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Wu N, Yuan F, Yue S, Jiang F, Ren D, Liu L, Bi Y, Guo Z, Ji L, Han K, Yang X, Feng M, Su K, Yang F, Wu X, Lu Q, Li X, Wang R, Liu B, Le S, Shi Y, He G. Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation. Cell Biosci 2021; 11:189. [PMID: 34736535 PMCID: PMC8569968 DOI: 10.1186/s13578-021-00701-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 10/25/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2. METHODS Methylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used. RESULTS Both LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG_10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention. CONCLUSIONS We highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue. Trial registration International Standard Randomized Controlled Trial Number Register (ISRCTN 42622771).
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Affiliation(s)
- Na Wu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Fan Yuan
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Siran Yue
- Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fengyan Jiang
- Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Decheng Ren
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Liangjie Liu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Bi
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Zhenming Guo
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Lei Ji
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Ke Han
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Xiao Yang
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Mofan Feng
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Kai Su
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Fengping Yang
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Xi Wu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Qing Lu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Xingwang Li
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Ruirui Wang
- Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Baocheng Liu
- Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shenglong Le
- Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Yi Shi
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China. .,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
| | - Guang He
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China. .,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
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Bence KK, Birnbaum MJ. Metabolic drivers of non-alcoholic fatty liver disease. Mol Metab 2021; 50:101143. [PMID: 33346069 PMCID: PMC8324696 DOI: 10.1016/j.molmet.2020.101143] [Citation(s) in RCA: 134] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/02/2020] [Accepted: 12/11/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide parallel to the global obesity epidemic. NAFLD encompasses a range of liver pathologies and most often originates from metabolically driven accumulation of fat in the liver, or non-alcoholic fatty liver (NAFL). In a subset of NAFL patients, the disease can progress to non-alcoholic steatohepatitis (NASH), which is a more severe form of liver disease characterized by hepatocyte injury, inflammation, and fibrosis. Significant progress has been made over the past decade in our understanding of NASH pathogenesis, but gaps remain in our mechanistic knowledge of the precise metabolic triggers for disease worsening. SCOPE OF REVIEW The transition from NAFL to NASH likely involves a complex constellation of multiple factors intrinsic and extrinsic to the liver. This review focuses on early metabolic events in the establishment of NAFL and initial stages of NASH. We discuss the association of NAFL with obesity as well as the role of adipose tissue in disease progression and highlight early metabolic drivers implicated in the pathological transition from hepatic fat accumulation to steatohepatitis. MAJOR CONCLUSIONS The close association of NAFL with features of metabolic syndrome highlight plausible mechanistic roles for adipose tissue health and the release of lipotoxic lipids, hepatic de novo lipogenesis (DNL), and disruption of the intestinal barrier in not only the initial establishment of hepatic steatosis, but also in mediating disease progression. Human genetic variants linked to NASH risk to date are heavily biased toward genes involved in the regulation of lipid metabolism, providing compelling support for the hypothesis that NASH is fundamentally a metabolic disease.
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Affiliation(s)
- Kendra K Bence
- Internal Medicine Research Unit, Pfizer Worldwide Research, Development, and Medical, Cambridge, MA, USA.
| | - Morris J Birnbaum
- Internal Medicine Research Unit, Pfizer Worldwide Research, Development, and Medical, Cambridge, MA, USA
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Kang SH, Lee HW, Yoo JJ, Cho Y, Kim SU, Lee TH, Jang BK, Kim SG, Ahn SB, Kim H, Jun DW, Choi JI, Song DS, Kim W, Jeong SW, Kim MY, Koh H, Jeong S, Lee JW, Cho YK. KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease. Clin Mol Hepatol 2021; 27:363-401. [PMID: 34154309 PMCID: PMC8273632 DOI: 10.3350/cmh.2021.0178] [Citation(s) in RCA: 174] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Affiliation(s)
- Seong Hee Kang
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, SoonChunHyang University Bucheon Hospital, Bucheon, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul Korea
| | - Tae Hee Lee
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, SoonChunHyang University Bucheon Hospital, Bucheon, Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Joon-Il Choi
- Department of Radiology, Seoul St.Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Do Seon Song
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hong Koh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea
| | - Sujin Jeong
- Division of Pediatric Gastroenterology Hepatology and Nutrition, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Jin-Woo Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Yong Kyun Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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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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29
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Kim HJ, Lee Y, Fang S, Kim W, Kim HJ, Kim JW. GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress. BMB Rep 2021. [PMID: 32317079 PMCID: PMC7330808 DOI: 10.5483/bmbrep.2020.53.6.280] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. NAFLD can further progress to irreversible liver failure such as non-alcoholic steatohepatitis (NASH) fibrosis and cirrhosis. However, specific regulator of NASH- fibrosis has yet to be established. Here, we found that glutathione peroxidase 7 (GPx7) was markedly expressed in NASH fibrosis. Although GPx7 is an antioxidant enzyme protecting other organs, whether GPx7 plays a role in NASH fibrosis has yet to be studied. We found that knockdown of GPx7 in transforming growth factor-β (TGF-β) and free fatty acids (FFA)- treated LX-2 cells elevated the expression of pro-fibrotic and pro-inflammatory genes and collagen synthesis. Consistently, GPx7 overexpression in LX-2 cells led to the suppression of ROS production and reduced the expression of pro-fibrotic and pro-inflammatory genes. Further, NASH fibrosis induced by choline-deficient amino acid defined, high fat diet (CDAHFD) feeding was significantly accelerated by knockdown of GPx7, as evidenced by up-regulated liver fibrosis and inflammation compared with CDAHFD control mice. Collectively, these results suggest that GPx7 might be a novel therapeutic target to prevent the progression and development of NAFLD.
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Affiliation(s)
- Hyeon Ju Kim
- Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul 03722; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea
| | - Yoseob Lee
- Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul 03722; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea
| | - Sungsoon Fang
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Korea
| | - Hyo Jung Kim
- 1Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Jae-Woo Kim
- Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul 03722; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea
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Cariello M, Piccinin E, Moschetta A. Transcriptional Regulation of Metabolic Pathways via Lipid-Sensing Nuclear Receptors PPARs, FXR, and LXR in NASH. Cell Mol Gastroenterol Hepatol 2021; 11:1519-1539. [PMID: 33545430 PMCID: PMC8042405 DOI: 10.1016/j.jcmgh.2021.01.012] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 01/19/2021] [Accepted: 01/19/2021] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease comprises a wide spectrum of liver injuries from simple steatosis to steatohepatitis and cirrhosis. Nonalcoholic steatohepatitis (NASH) is defined when liver steatosis is associated with inflammation, hepatocyte damage, and fibrosis. A genetic predisposition and environmental insults (ie, dietary habits, obesity) are putatively responsible for NASH progression. Here, we present the impact of the lipid-sensing nuclear receptors in the pathogenesis and treatment of NASH. In detail, we discuss the pros and cons of the putative transcriptional action of the fatty acid sensors (peroxisome proliferator-activated receptors), the bile acid sensor (farnesoid X receptor), and the oxysterol sensor (liver X receptors) in the pathogenesis and bona fide treatment of NASH.
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Affiliation(s)
- Marica Cariello
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro," Bari, Italy
| | - Elena Piccinin
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy
| | - Antonio Moschetta
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro," Bari, Italy; National Institute for Biostructures and Biosystems (INBB), Rome, Italy; Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Istituto Tumori Giovanni Paolo II, Bari, Italy.
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31
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Fang X, Du Z, Duan C, Zhan S, Wang T, Zhu M, Shi J, Meng J, Zhang X, Yang M, Zuo Y. Beinaglutide shows significantly beneficial effects in diabetes/obesity-induced nonalcoholic steatohepatitis in ob/ob mouse model. Life Sci 2021; 270:118966. [PMID: 33482185 DOI: 10.1016/j.lfs.2020.118966] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/21/2020] [Accepted: 12/22/2020] [Indexed: 12/12/2022]
Abstract
AIMS Beinaglutide has been approved for glucose lowering in type 2 diabetes mellitus (T2DM) in China. In addition to glycemic control, significant weight loss is observed from real world data. This study is designed to investigate the pharmacological and pharmacokinetic profiles of beinaglutide in different models. METHODS The pharmacological efficacy of beinaglutide was evaluated in C57BL/6 and ob/ob mice after single administration. Pharmacokinetic profiles in mice were investigated after single or multiple administration. Sub-chronic pharmacological efficacy was investigated in ob/ob mice for two weeks treatment and diet-induced ob/ob mice model of nonalcoholic steatohepatitis (NASH) for four weeks treatment. KEY FINDINGS Beinaglutide could dose-dependently reduce the glucose levels and improve insulin secretion in glucose tolerance tests, inhibit food intake and gastric emptying after single administration. At higher doses, beinaglutide could inhibit food intake over 4 h, which results in weight loss in ob/ob mice after about two weeks treatment. No tachyphylaxis is observed for beinaglutide in food intake with repeated administration. In NASH model, beinaglutide could reduce liver weight and hepatic steatosis and improve insulin sensitivity. Signiant changes of gene levels were observed in fatty acid β-oxidation (Ppara, Acadl, Acox1), mitochondrial function (Mfn1, Mfn2), antioxidation (Sod2), Sirt1, and et al. SIGNIFICANCE: Our results characterize the pharmacological and pharmacokinetic profiles of beinaglutide in mice and supported that chronic use of beinaglutde could lead to weight loss and reduce hepatic steatosis, which suggest beinaglutide may be effective therapy for the treatment of obesity and NASH.
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Affiliation(s)
- Xiankang Fang
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China.
| | - Zhiqiang Du
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
| | - Chunling Duan
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
| | - Shanshan Zhan
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
| | - Tian Wang
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
| | - Mengyu Zhu
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
| | - Jiajie Shi
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
| | - Juan Meng
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
| | - Xianhua Zhang
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
| | - Maiyun Yang
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
| | - Yajun Zuo
- Innovation Center, Shanghai Benemae Pharmaceutical Corporation, 916 Ziping Road, Zhoupu, PuDong, Shanghai, China
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32
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Bischoff SC, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Plauth M. ESPEN practical guideline: Clinical nutrition in liver disease. Clin Nutr 2020; 39:3533-3562. [PMID: 33213977 DOI: 10.1016/j.clnu.2020.09.001] [Citation(s) in RCA: 188] [Impact Index Per Article: 37.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The Practical guideline is based on the current scientific ESPEN guideline on Clinical Nutrition in Liver Disease. METHODS It has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. RESULTS A total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in liver patients and on liver complications associated with medical nutrition. CONCLUSION This practical guideline gives guidance to health care providers involved in the management of liver disease to offer optimal nutritional care.
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Affiliation(s)
- Stephan C Bischoff
- Department for Clinical Nutrition, University of Hohenheim, Stuttgart, Germany.
| | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tatjana Schütz
- IFB Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany
| | - Mathias Plauth
- Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany
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Campos-Murguía A, Ruiz-Margáin A, González-Regueiro JA, Macías-Rodríguez RU. Clinical assessment and management of liver fibrosis in non-alcoholic fatty liver disease. World J Gastroenterol 2020; 26:5919-5943. [PMID: 33132645 PMCID: PMC7584064 DOI: 10.3748/wjg.v26.i39.5919] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 05/24/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key factor influencing its prognosis is the progression of liver fibrosis. This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD, analyzing the currently available literature. In the assessment of NAFLD patients, it is important to identify clinical, genetic, and environmental determinants of fibrosis development and its progression. To properly detect fibrosis, it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores, followed by a complementary imaging study (transient elastography, magnetic resonance elastography or acoustic radiation force impulse) and finally a liver biopsy, when needed. To help with the selection of the most appropriate method a Fagan's nomogram analysis is provided in this review, describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis. Finally, treatment should always include diet and exercise, as well as controlling the components of the metabolic syndrome, +/- vitamin E, considering the presence of sleep apnea, and when available, allocate those patients with advanced fibrosis or high risk of progression into clinical trials. The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD, aiming to decrease/stop its progression and improve their prognosis.
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Affiliation(s)
- Alejandro Campos-Murguía
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Astrid Ruiz-Margáin
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - José A González-Regueiro
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Ricardo U Macías-Rodríguez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
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Hydes TJ, Ravi S, Loomba R, E Gray M. Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH. Clin Mol Hepatol 2020; 26:383-400. [PMID: 32674529 PMCID: PMC7641567 DOI: 10.3350/cmh.2020.0067] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 05/19/2020] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and affects approximately one third of adults in the United States. The disease is becoming a global epidemic as a result of the rising rates of obesity and metabolic disease. Emerging data suggest weight loss of ≥10% overall body weight is beneficial in resolving steatosis and reversing fibrosis. Prospective trials comparing various diets are limited by lack of sufficient power as well as pre- and post-treatment histopathology, and therefore no specific diet is recommended at this time. In this narrative review we examine the pathophysiology behind specific macronutrient components that can either promote or reverse NAFLD to help inform more specific dietary recommendations. Overall, the data supports reducing saturated fat, refined carbohydrates, and red and processed meats in the diet, and increasing the consumption of plant-based foods. Diets that incorporate these recommendations include plant-based diets such as the Dietary Approaches to Stop Hypertension, Mediterranean, vegetarian, and vegan diets.
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Affiliation(s)
- Theresa J Hydes
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sujan Ravi
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Rohit Loomba
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
| | - Meagan E Gray
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
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Tanaka Y, Ikeda T, Ogawa H, Kamisako T. Ezetimibe Markedly Reduces Hepatic Triglycerides and Cholesterol in Rats Fed on Fish Oil by Increasing the Expression of Cholesterol Efflux Transporters. J Pharmacol Exp Ther 2020; 374:175-183. [PMID: 32366600 DOI: 10.1124/jpet.120.265660] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 04/30/2020] [Indexed: 03/08/2025] Open
Abstract
Besides diet therapy, hypolipidemic pharmacological therapy may be a crucial component of nonalcoholic fatty liver disease (NAFLD) treatment. Ezetimibe may be a promising drug for treatment of NAFLD. n-3 polyunsaturated fatty acids, which are abundant in fish oil, reduce serum and hepatic cholesterol and triglycerides in rodents. The aim of this study was to examine the combined effects of dietary fish oil and ezetimibe on lipid metabolism in rats. Seven-week-old male Sprague-Dawley rats were allocated to four different diets containing 1) 10% soybean oil (C), 2) 10% fish oil (F), 3) 10% soybean oil + 0.005% ezetimibe, and 4) 10% fish oil + 0.005% ezetimibe (F+E) for 4 weeks, when the liver, jejunum, blood, and fecal samples were collected. Compared with the C group, the F+E diet decreased hepatic triglycerides and cholesterol 84% and 86%, but it did not increase fecal cholesterol. In liver, the expression of lipogenic enzymes was decreased in the F+E diet, whereas β-oxidation-related genes were not increased. Abcg5/g8 mRNA expression was increased 1380%/442% when ezetimibe was added to the F diet. These gene expression changes are related to the decrease in hepatic lipids. In jejunum, Abcg5/g8 mRNA was increased 244%/841% when ezetimibe was added to the F diet. Hepatic induction of Abcg5/8 rather than intestinal induction correlates with the marked decrease in liver cholesterol when ezetimibe was added to the F diet. These data suggest that fish oil diet and ezetimibe in combination may be a beneficial therapy for NAFLD by increasing hepatic Abcg5/g8 and decreasing lipogenic genes. SIGNIFICANCE STATEMENT: There is currently no single treatment for NAFLD. Thus, lifestyle modifications including dietary regulation and physical activity are also important options. In this study, ezetimibe, a cholesterol absorption inhibitor, was evaluated for the treatment of liver steatosis in rats fed on the different diets. We found that ezetimibe and fish oil in combination markedly improved fatty liver by increasing cholesterol efflux transporters. The combination therapy of fish oil agents and ezetimibe may be effective for NAFLD.
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Affiliation(s)
- Yuji Tanaka
- Department of Clinical Laboratory Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan (Y.T., T.K.), and Faculty of Human Sciences, Tezukayama Gakuin University, Sakai, Osaka, Japan (T.I., H.O.)
| | - Takanori Ikeda
- Department of Clinical Laboratory Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan (Y.T., T.K.), and Faculty of Human Sciences, Tezukayama Gakuin University, Sakai, Osaka, Japan (T.I., H.O.)
| | - Hiroshi Ogawa
- Department of Clinical Laboratory Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan (Y.T., T.K.), and Faculty of Human Sciences, Tezukayama Gakuin University, Sakai, Osaka, Japan (T.I., H.O.)
| | - Toshinori Kamisako
- Department of Clinical Laboratory Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan (Y.T., T.K.), and Faculty of Human Sciences, Tezukayama Gakuin University, Sakai, Osaka, Japan (T.I., H.O.)
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Nath P, Panigrahi MK, Sahu MK, Narayan J, Sahoo RK, Patra AA, Jena S, Patnaik AK, Jena A, Singh SP. Effect of Exercise on NAFLD and Its Risk Factors: Comparison of Moderate versus Low Intensity Exercise. J Clin Transl Hepatol 2020; 8:120-126. [PMID: 32832391 PMCID: PMC7438352 DOI: 10.14218/jcth.2019.00012] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Revised: 12/27/2019] [Accepted: 04/01/2020] [Indexed: 12/18/2022] Open
Abstract
Background and Aims: Lifestyle (exercise and dietary) modification is the mainstay of treatment for non-alcoholic fatty liver disease (NAFLD). However, there is paucity of data on effect of intensity of exercise in management of NAFLD, and we aimed to study the effect of variable intensities of exercise on NAFLD. Methods: The study was performed in the Department of Gastroenterology of the SCB Medical College, Cuttack and the Biju Patnaik State Police Academy, Bhubaneswar. The subjects were police trainees [18 in a moderate intensity exercise group (MIG) and 19 in a low intensity exercise group (LIG)] recruited for a 6-month physical training course (261.8 Kcalorie, 3.6 metabolic equivalent in MIG and 153.6 Kcalorie, 2.1 metabolic equivalent in LIG). NAFLD was diagnosed by ultrasonography, with exclusion of all secondary causes of steatosis. All participants were evaluated by anthropometry (weight, height, body mass index (BMI), waist circumference), assessed for blood pressure and biochemical parameters (blood glucose, liver function test, lipid profile, serum insulin), and subjected to transabdominal ultrasonography before and after 6 months of physical training, and the results were compared. Results: Both the groups had similar BMI, fasting plasma glucose, AST, gamma-glutamyl transpeptidase, insulin, and homeostatic model assessment-insulin resistance (known as HOMA-IR) (p>0.05). However, subjects in the LIG were older and had lower alanine transaminase, higher triglycerides and lower high-density lipoproteins than MIG subjects. There was a significant reduction in BMI (27.0±2.1 to 26.8±2.0; p=0.001), fasting blood glucose (106.7±21.6 to 85.8±19.0; p<0.001), serum triglycerides (167.5±56.7 to 124.6±63.5; p=0.017), total cholesterol (216.8±29.2 to 196.7±26.6; p=0.037), low-density lipoprotein cholesterol (134.6±21.4 to 130.5±21.9; p=0.010), serum aspartate transaminase (39.3±32.2 to 30.9±11.4; p<0.001), serum alanine transaminase (56.6±28.7 to 33.0±11.3; p<0.001) and HOMA-IR (2.63±2.66 to 1.70±2.59; p<0.001) in the MIG. However, changes in these parameters in the LIG were non-significant. Hepatic steatosis regressed in 66.7% of the NAFLD subjects in the MIG but in only 26.3% of the LIG NAFLD subjects (p=0.030). Conclusions: Moderate rather than low intensity physical activity causes significant improvement in BMI, serum triglycerides, cholesterol, serum transaminases and HOMA-IR, and regression of ultrasonographic fatty change in liver among NAFLD subjects.
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Affiliation(s)
- Preetam Nath
- Department of Gastroenterology & Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Manas Kumar Panigrahi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Manoj Kumar Sahu
- Department of Gastroenterology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Jimmy Narayan
- Department of Gastroenterology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Ranjan Kumar Sahoo
- Department of Radiodiagnosis & Imaging, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Ananya Apurba Patra
- Department of Radiodiagnosis & Imaging, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Satyaswarup Jena
- Department of Radiology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Arun Kumar Patnaik
- Dispensary, Biju Patnaik State Police Academy, Bhubaneswar, Odisha, India
| | - Anjan Jena
- Dispensary, Biju Patnaik State Police Academy, Bhubaneswar, Odisha, India
| | - Shivaram Prasad Singh
- Department of Gastroenterology, S.C.B. Medical College, 753007 Cuttack, Odisha, India
- Correspondence to: Shivaram Prasad Singh, Department of Gastroenterology, SCB Medical College, Cuttack 753007, Orissa, India. Tel: +91-671-2505466, +91-671-2323624, E-mails: ;
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Goldner D, Lavine JE. Nonalcoholic Fatty Liver Disease in Children: Unique Considerations and Challenges. Gastroenterology 2020; 158:1967-1983.e1. [PMID: 32201176 DOI: 10.1053/j.gastro.2020.01.048] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 12/30/2019] [Accepted: 01/05/2020] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence in concert with the global epidemic of obesity and is being diagnosed at increasingly younger ages. The unique histologic features and early presentation of disease in pediatrics suggest that children and adults may differ with regard to etiopathogenesis, with children displaying a greater vulnerability to genetic and environmental factors. Of significant relevance to pediatrics, in utero and perinatal stressors may alter the lifelong health trajectory of a child, increasing the risk of NAFLD and other cardiometabolic diseases. The development and progression of disease in childhood is likely to carry increased risk of long-term morbidity. Novel biomarkers and therapeutic agents are needed to avoid the otherwise inevitable health and societal consequences of this rapidly expanding pediatric population.
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Affiliation(s)
- Dana Goldner
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Columbia University Medical Center, New York, New York
| | - Joel E Lavine
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Columbia University Medical Center, New York, New York.
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Lim SL, Johal J, Ong KW, Han CY, Chan YH, Lee YM, Loo WM. Lifestyle Intervention Enabled by Mobile Technology on Weight Loss in Patients With Nonalcoholic Fatty Liver Disease: Randomized Controlled Trial. JMIR Mhealth Uhealth 2020; 8:e14802. [PMID: 32281943 PMCID: PMC7186867 DOI: 10.2196/14802] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 03/09/2020] [Accepted: 03/20/2020] [Indexed: 02/07/2023] Open
Abstract
Background The prevalence of nonalcoholic fatty liver disease (NAFLD) reaches up to 30% in the Asian adult population, with a higher prevalence in obese patients. Weight reduction is typically recommended for patients at high risk or diagnosed with NAFLD, but is a challenge to achieve. Objective We aimed to evaluate the effect of a lifestyle intervention with a mobile app on weight loss in NAFLD patients. Methods This prospective randomized controlled trial included 108 adults with NAFLD confirmed by steatosis on ultrasound and a body mass index ≥23 kg/m2 who were recruited from a fatty liver outpatient clinic. The patients were randomly allocated to either a control group (n=53) receiving standard care, consisting of dietary and lifestyle advice by a trained nurse, or an intervention group (n=55) utilizing the Nutritionist Buddy (nBuddy) mobile app in addition to receiving dietary and lifestyle advice by a dietitian. Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST), waist circumference, and blood pressure were measured at baseline, and then at 3 and 6 months. Intention-to-treat and per-protocol analyses were used for statistical comparisons. Results The intervention group had a 5-fold higher likelihood (relative risk 5.2, P=.003, 95% CI 1.8-15.4) of achieving ≥5% weight loss compared to the control group at 6 months. The intervention group also showed greater reductions in weight (mean 3.2, SD 4.1 kg vs mean 0.5, SD 2.9 kg; P<.001), waist circumference (mean 2.9, SD 5.0 cm vs mean –0.7, SD 4.4 cm; P<.001), systolic blood pressure (mean 12.4, SD 14.8 mmHg vs mean 2.4, SD 12.4 mmHg; P=.003), diastolic blood pressure (mean 6.8, SD 8.9 mmHg vs mean –0.9, SD 10.0 mmHg; P=.001), ALT (mean 33.5, SD 40.4 IU/L vs mean 11.5, SD 35.2 IU/L; P=.004), and AST (mean 17.4, SD 27.5 U/L vs mean 7.4, SD 17.6 IU/L, P=.03) at 6 months. Conclusions Lifestyle intervention enabled by a mobile app can be effective in improving anthropometric indices and liver enzymes in patients with NAFLD. This treatment modality has the potential to be extended to a larger population scale. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12617001001381;
https://tinyurl.com/w9xnfmp
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Affiliation(s)
- Su Lin Lim
- Dietetics Department, National University Hospital, National University Health System, Singapore, Singapore
| | - Jolyn Johal
- Dietetics Department, National University Hospital, National University Health System, Singapore, Singapore
| | - Kai Wen Ong
- Dietetics Department, National University Hospital, National University Health System, Singapore, Singapore
| | - Chad Yixian Han
- Dietetics Department, National University Hospital, National University Health System, Singapore, Singapore
| | - Yiong Huak Chan
- Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yin Mei Lee
- Department of Medicine, Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
| | - Wai Mun Loo
- Department of Medicine, Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
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Michlin M, Argaev-Frenkel L, Weinstein-Fudim L, Ornoy A, Rosenzweig T. Maternal N-Acetyl Cysteine Intake Improved Glucose Tolerance in Obese Mice Offspring. Int J Mol Sci 2020; 21:E1981. [PMID: 32183232 PMCID: PMC7139991 DOI: 10.3390/ijms21061981] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 02/20/2020] [Accepted: 03/09/2020] [Indexed: 12/17/2022] Open
Abstract
Exposure to certain environmental factors during the early stages of development was found to affect health in adulthood. Among other environmental factors, oxidative stress has been suggested to be involved in fetal programming, leading to elevated risk for metabolic disorders, including type 2 diabetes; however, the possibility that antioxidant consumption during early life may affect the development of diabetes has scarcely been studied. The aim of this study was to investigate the effects of N-acetyl-l-cysteine (NAC) given during pregnancy and lactation on the susceptibility of offspring to develop glucose intolerance at adulthood. C57bl6/J mice were given NAC during pregnancy and lactation. High fat diet (HFD) was given to offspring at an age of 6 weeks for an additional 9 weeks, till the end of the study. Isolated islets of NAC-treated offspring (6 weeks old, before HFD feeding) had an increased efficacy of glucose-stimulated insulin secretion and a higher resistance to oxidative damage. Following HFD feeding, glucose tolerance and insulin sensitivity of NAC-treated offspring were improved. In addition, islet diameter was lower in male offspring of NAC-treated mice compared to their HFD-fed littermates. NAC consumption during early life improves glucose tolerance in adulthood in mice.
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Affiliation(s)
- Michal Michlin
- Departments of Molecular Biology and Nutrition Sciences, Ariel University, Ariel 40700, Israel; (M.M.); (L.A.-F.)
| | - Lital Argaev-Frenkel
- Departments of Molecular Biology and Nutrition Sciences, Ariel University, Ariel 40700, Israel; (M.M.); (L.A.-F.)
| | - Liza Weinstein-Fudim
- Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel; (L.W.-F.); (A.O.)
| | - Asher Ornoy
- Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel; (L.W.-F.); (A.O.)
- Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Tovit Rosenzweig
- Departments of Molecular Biology and Nutrition Sciences, Ariel University, Ariel 40700, Israel; (M.M.); (L.A.-F.)
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Khneizer G, Rizvi S, Gawrieh S. Non-alcoholic Fatty Liver Disease and Diabetes Mellitus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1307:417-440. [PMID: 32424494 DOI: 10.1007/5584_2020_532] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading liver disease globally. NAFLD patients can have a progressive phenotype, non-alcoholic steatohepatitis (NASH) that could lead to cirrhosis, liver failure and cancer. There is a close bi-directional relationship between NAFLD and type 2 diabetes mellitus (T2DM); NAFLD increases the risk for T2DM and its complications whereas T2DM increases the severity of NAFLD and its complications. The large global impact of NAFLD and T2DM on healthcare systems requires a paradigm shift from specialty care to early identification and risk stratification of NAFLD in primary care and diabetes clinics. Approach to diagnosis, risk stratification and management of NAFLD is discussed. In addition to optimizing the control of coexisting cardiometabolic comorbidities, early referral of NAFLD patients at high risk of having NASH or significant fibrosis to hepatology specialist care may improve management and allow access for clinical trials. Lifestyle modifications, vitamin E, pioglitazone and metformin are currently available options that may benefit patients with T2DM and NAFLD. The burst of clinical trials investigating newer therapeutic agents for NAFLD and NASH offer hope for new, effective and safe therapies in the near future.
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Affiliation(s)
- Gebran Khneizer
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Syed Rizvi
- A&M College of Medicine, Round Rock, Austin, TX, USA
| | - Samer Gawrieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
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Ganguli S, DeLeeuw P, Satapathy SK. A Review Of Current And Upcoming Treatment Modalities In Non-Alcoholic Fatty Liver Disease And Non-Alcoholic Steatohepatitis. Hepat Med 2019; 11:159-178. [PMID: 31814783 PMCID: PMC6863115 DOI: 10.2147/hmer.s188991] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 10/03/2019] [Indexed: 12/15/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the West. Non-alcoholic steatohepatitis (NASH) is the progressive form of NAFLD and can lead to cirrhosis, hepatocellular carcinoma, and is associated with increased cardiovascular risks. Multiple components and risk factors are thought to be involved in the pathogenesis of NAFLD and NASH. Optimal therapy has not yet been found, but many advances have been made with the discovery of potential therapeutic options. In this paper, we aim to provide a comprehensive review of approved, studied, and upcoming treatment options for NAFLD and NASH. Non-pharmacologic therapy (lifestyle modifications and bariatric surgery) and pharmacologic therapy are both reviewed. Pharmacologic therapy target components thought to be involved in the pathogenesis of this disease process including insulin resistance, oxidative stress, inflammation, lipid metabolism, and fibrosis are reviewed in this paper. Results of the emerging treatment targets in phase 2 and 3 clinical trials are also included.
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Affiliation(s)
- Surosree Ganguli
- Division of Internal Medicine, University of Louisville, Louisville, KY40202, USA
| | - Peter DeLeeuw
- Division of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN38163, USA
| | - Sanjaya K Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY11030, USA
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42
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Heck SO, Zborowski VA, Chagas PM, da Luz SCA, Bortolatto CF. p-Chloro-diphenyl diselenide attenuates plasma lipid profile changes and hepatotoxicity induced by nonionic surfactant tyloxapol in rats. Toxicol Mech Methods 2019; 30:73-80. [DOI: 10.1080/15376516.2019.1669240] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- Suélen Osório Heck
- Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria – RS, Brazil
| | - Vanessa Angonesi Zborowski
- Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria – RS, Brazil
| | - Pietro Maria Chagas
- Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria – RS, Brazil
| | | | - Cristiani Folharini Bortolatto
- Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Post-Graduation Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), Capão do Leão Campus, Pelotas – RS, Brazil
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Rahmanabadi A, Mahboob S, Amirkhizi F, Hosseinpour-Arjmand S, Ebrahimi-Mameghani M. Oral α-lipoic acid supplementation in patients with non-alcoholic fatty liver disease: effects on adipokines and liver histology features. Food Funct 2019; 10:4941-4952. [PMID: 31343010 DOI: 10.1039/c9fo00449a] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Considering the importance of adipokines in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and due to the possible beneficial effects of α-lipoic acid (α-LA) on these adipose-derived hormones, this study aimed to investigate the effect of α-LA supplementation on adipokines and liver steatosis in obese patients with NAFLD. In a double-blind, placebo-controlled randomized clinical trial with two parallel groups, fifty patients with NAFLD were randomized to receive daily supplementation with either two capsules of α-LA (each capsule containing 600 mg α-LA) or two placebo capsules, daily for 12 weeks. At the baseline, all participants received consultation on how to implement a healthy diet into their daily lives. Anthropometric measures, dietary intakes, liver enzymes and adipokines were assessed at the baseline and after 12 weeks of intervention. A significant reduction was observed in the serum levels of insulin (P = 0.024) and leptin (P = 0.019) in the α-LA group compared to the placebo group, but changes in anthropometric and body composition measures, serum glucose (FSG), resistin, irisin and liver enzymes did not differ between the groups. α-LA supplementation resulted in a statistically significant elevation in the quantitative insulin sensitivity check index (QUICKI) (P = 0.033), serum levels of adiponectin (P = 0.008) and adiponectin-to-leptin ratio (P = 0.007) compared to the placebo. The liver steatosis intensity improved significantly. Nonetheless, no significant differences were observed between the study groups in the liver steatosis intensity, at the end of the study. According to the results, α-LA supplementation for 12 weeks improved insulin resistance, serum levels of insulin, adiponectin and leptin without changing anthropometric measures, serum liver enzymes, resistin and irisin.
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Affiliation(s)
- Alireza Rahmanabadi
- Student Research Committee, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Povsic M, Oliver L, Jiandani NR, Perry R, Bottomley J. A structured literature review of interventions used in the management of nonalcoholic steatohepatitis (NASH). Pharmacol Res Perspect 2019; 7:e00485. [PMID: 31149341 PMCID: PMC6536401 DOI: 10.1002/prp2.485] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 04/18/2019] [Accepted: 04/26/2019] [Indexed: 12/18/2022] Open
Abstract
Nonalcoholic steatohepatitis (NASH) is a chronic, progressive disease, that can advance to fibrosis, cirrhosis, and hepatocellular carcinoma. Despite being a leading cause of liver transplantation, there are no approved pharmacological treatments. Our aim was to identify literature on management options in NASH. Our structured review of interventions treating NASH patients from English language publications between 1 January 2007 and 25 September 2017 elicited 48 eligible references. Lifestyle management was identified as the mainstay of NASH therapy. Vitamin E and pioglitazone reported reductions in steatosis; however, although recommended for some, no therapies are indicated in NASH. Multiple investigational treatments reported efficacy in mild-to-moderate fibrosis in Phase II/III NASH trials. Lifestyle management, although the focus of clinical guidelines, is insufficient for patients progressing to advanced fibrosis. With no clear guidelines for patients requiring interventions beyond lifestyle modification, long-term outcomes data are needed, particularly in patients with moderate-to-severe fibrosis.
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45
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Esler WP, Bence KK. Metabolic Targets in Nonalcoholic Fatty Liver Disease. Cell Mol Gastroenterol Hepatol 2019; 8:247-267. [PMID: 31004828 PMCID: PMC6698700 DOI: 10.1016/j.jcmgh.2019.04.007] [Citation(s) in RCA: 97] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 04/09/2019] [Accepted: 04/11/2019] [Indexed: 12/18/2022]
Abstract
The prevalence and diagnosis of nonalcoholic fatty liver disease (NAFLD) is on the rise worldwide and currently has no FDA-approved pharmacotherapy. The increase in disease burden of NAFLD and a more severe form of this progressive liver disease, nonalcoholic steatohepatitis (NASH), largely mirrors the increase in obesity and type 2 diabetes (T2D) and reflects the hepatic manifestation of an altered metabolic state. Indeed, metabolic syndrome, defined as a constellation of obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension, is the major risk factor predisposing the NAFLD and NASH. There are multiple potential pharmacologic strategies to rebalance aspects of disordered metabolism in NAFLD. These include therapies aimed at reducing hepatic steatosis by directly modulating lipid metabolism within the liver, inhibiting fructose metabolism, altering delivery of free fatty acids from the adipose to the liver by targeting insulin resistance and/or adipose metabolism, modulating glycemia, and altering pleiotropic metabolic pathways simultaneously. Emerging data from human genetics also supports a role for metabolic drivers in NAFLD and risk for progression to NASH. In this review, we highlight the prominent metabolic drivers of NAFLD pathogenesis and discuss the major metabolic targets of NASH pharmacotherapy.
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Key Words
- acc, acetyl-coa carboxylase
- alt, alanine aminotransferase
- aso, anti-sense oligonucleotide
- ast, aspartate aminotransferase
- chrebp, carbohydrate response element binding protein
- ci, confidence interval
- dgat, diacylglycerol o-acyltransferase
- dnl, de novo lipogenesis
- fas, fatty acid synthase
- ffa, free fatty acid
- fgf, fibroblast growth factor
- fxr, farnesoid x receptor
- glp-1, glucagon-like peptide-1
- hdl, high-density lipoprotein
- homa-ir, homeostatic model assessment of insulin resistance
- ldl, low-density lipoprotein
- nafld, nonalcoholic fatty liver disease
- nas, nonalcoholic fatty liver disease activity score
- nash, nonalcoholic steatohepatitis
- or, odds ratio
- pdff, proton density fat fraction
- ppar, peroxisome proliferator-activated receptor
- sglt2, sodium glucose co-transporter 2
- srebp-1c, sterol regulatory element binding protein-1c
- t2d, type 2 diabetes
- t2dm, type 2 diabetes mellitus
- tg, triglyceride
- th, thyroid hormone
- thr, thyroid hormone receptor
- treg, regulatory t cells
- tzd, thiazolidinedione
- vldl, very low-density lipoprotein
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Affiliation(s)
- William P Esler
- Internal Medicine Research Unit, Pfizer Worldwide Research, Development, and Medical, Cambridge, Massachusetts
| | - Kendra K Bence
- Internal Medicine Research Unit, Pfizer Worldwide Research, Development, and Medical, Cambridge, Massachusetts.
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46
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Affiliation(s)
- Ken Garber
- Ken Garber is a freelance reporter based in Ann Arbor, Michigan, USA
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47
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Kim KS, Lee BW, Kim YJ, Lee DH, Cha BS, Park CY. Nonalcoholic Fatty Liver Disease and Diabetes: Part II: Treatment. Diabetes Metab J 2019; 43:127-143. [PMID: 30993937 PMCID: PMC6470100 DOI: 10.4093/dmj.2019.0034] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 03/19/2019] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) and diabetes are common metabolic disorders that are often comorbid conditions. Among many proposed treatments, weight reduction is the only approved option for NAFLD to date. However, it is not easy to maintain weight loss by lifestyle modification alone; pharmacological treatments are helpful in this regard. Although many drugs have been investigated, pioglitazone could be a first-line therapy in patients with NAFLD and diabetes. Many more drugs are currently being developed and investigated, and it is likely that combination strategies will be used for future treatment of NAFLD and diabetes. Attention should be paid to the management of NAFLD and diabetes and efforts should be made to intervene early and individualize treatment of NAFLD in patients with diabetes.
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Affiliation(s)
- Kyung Soo Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Byung Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
| | - Yong Jin Kim
- Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Dae Ho Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Bong Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Cheol Young Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Moshtaq MA, Rahimi MH, Mollahosseini M, Khorrami-Nezhad L, Maghbooli Z, Mirzaei K, Pooyan S, Setayesh L. Association between dietary glycemic index and liver enzymes level among apparently healthy adults. Diabetes Metab Syndr 2019; 13:1597-1602. [PMID: 31336527 DOI: 10.1016/j.dsx.2019.03.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 03/05/2019] [Indexed: 12/31/2022]
Abstract
OBJECTIVE The previous studies have revealed that there is a link between dietary glycemic index and lipid profile in overweight and obesity. The aim of study was to investigate whether the glycemic index is associated with liver enzymes. METHOD Anthropometric and biochemical parameters were measured in 265 participants. Dietary glycemic index (GI) was assessed by using a validated food-frequency questionnaire. With adjusting confounder variable, Binary logistic regression was also used to predict the relationship between liver enzymes and quartile of intake. RESULTS There was a significant difference between low and high GI diet for BMR (P = 0.01), FFM (P = 0.03), TG (P = 0.02), HDL (P = 0.002). The association between HDL and glycemic index remained significant after adjustment of sex and age (P = 0.03). Using the regression model following adjustment revealed that for each 1% increase in the degree of the GI, there was 11% elevation in liver enzyme abnormalities. In both groups of men and women, enzyme abnormalities positively correlated with GI, while only men showed remarkable correlation in all models (crude model: β = 0.07, OR = 1.07, CI = 0.98to 1.16). Additionally, an increase in the degree of GI caused an elevation in enzyme abnormalities by 7%. With adjusting sex, age, BMI, and Physical activity, a significance correlation was found between GI and Enzyme abnormalities (p-value = 0.03, OR = 1.115). CONCLUSION Our study indicated that high glycemic index diet led to the elevated levels of the liver enzymes, while being significant only in men.
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Affiliation(s)
- Mohammad Ali Moshtaq
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Mohammad Hossein Rahimi
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Mehdi Mollahosseini
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Iran
| | - Leila Khorrami-Nezhad
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Zhila Maghbooli
- Multiple Sclerosis Research Center, Sina hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Khadijeh Mirzaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Sara Pooyan
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Leila Setayesh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
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Vilar-Gomez E, Athinarayanan SJ, Adams RN, Hallberg SJ, Bhanpuri NH, McKenzie AL, Campbell WW, McCarter JP, Phinney SD, Volek JS, Chalasani N. Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study. BMJ Open 2019; 9:e023597. [PMID: 30803948 PMCID: PMC6398805 DOI: 10.1136/bmjopen-2018-023597] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. METHODS This was a non-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >-0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 year were the main endpoints. RESULTS At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 19% of patients in UC (p<0.001). N-LFS mean score was reduced in the CCI group (-1.95±0.22, p<0.001), whereas it was not changed in the UC (0.47±0.41, p=0.26) (CCI vs UC, p<0.001). NFS was reduced in the CCI group (-0.65±0.06, p<0.001) compared with UC (0.26±0.11, p=0.02) (p<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (p<0.001). CONCLUSIONS One year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with T2D. TRIAL REGISTRATION NUMBER NCT02519309; Results.
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Affiliation(s)
- Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | | | | | - Sarah J Hallberg
- Virta Health, San Francisco, California, USA
- Indiana University Health Arnett, Lafayette, Indiana, USA
| | | | | | - Wayne W Campbell
- Department of Nutrition Science, Purdue University, West Lafayette, Indiana, USA
| | - James P McCarter
- Virta Health, San Francisco, California, USA
- Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA
| | | | - Jeff S Volek
- Virta Health, San Francisco, California, USA
- Department of Human Sciences, Ohio State University, Columbus, Ohio, USA
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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50
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Plauth M, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Bischoff SC. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr 2019; 38:485-521. [PMID: 30712783 DOI: 10.1016/j.clnu.2018.12.022] [Citation(s) in RCA: 396] [Impact Index Per Article: 66.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 12/18/2018] [Indexed: 02/06/2023]
Abstract
This update of evidence-based guidelines (GL) aims to translate current evidence and expert opinion into recommendations for multidisciplinary teams responsible for the optimal nutritional and metabolic management of adult patients with liver disease. The GL was commissioned and financially supported by ESPEN. Members of the guideline group were selected by ESPEN. We searched for meta-analyses, systematic reviews and single clinical trials based on clinical questions according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing the SIGN method. A total of 85 recommendations were made for the nutritional and metabolic management of patients with acute liver failure, severe alcoholic steatohepatitis, non-alcoholic fatty liver disease, liver cirrhosis, liver surgery and transplantation as well as nutrition associated liver injury distinct from fatty liver disease. The recommendations are preceded by statements covering current knowledge of the underlying pathophysiology and pathobiochemistry as well as pertinent methods for the assessment of nutritional status and body composition.
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Affiliation(s)
- Mathias Plauth
- Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany.
| | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tatjana Schütz
- IFB Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany
| | - Stephan C Bischoff
- Department for Clinical Nutrition, University of Hohenheim, Stuttgart, Germany
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