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Hauser G, Benjak Horvat I, Rajilić-Stojanović M, Krznarić-Zrnić I, Kukla M, Aljinović-Vučić V, Mikolašević I. Intestinal Microbiota Modulation by Fecal Microbiota Transplantation in Nonalcoholic Fatty Liver Disease. Biomedicines 2025; 13:779. [PMID: 40299326 PMCID: PMC12024620 DOI: 10.3390/biomedicines13040779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 03/14/2025] [Accepted: 03/20/2025] [Indexed: 04/30/2025] Open
Abstract
Numerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These factors are insulin resistance, lipid metabolism alteration, oxidative stress, endoplasmic reticulum stress, inflammatory cytokine liberation, gut microbiota dysbiosis or gut-liver axis activation. This is a systematic review which has an aim to show the connection between intestinal microbiota and the role of its disbalance in the development of NAFLD. The gut microbiota is made from a wide spectrum of microorganisms that has a systemic impact on human health, with a well-documented role in digestion, energy metabolism, the stimulation of the immune system, synthesis of essential nutrients, etc. It has been shown that dysbiosis is associated with all three stages of chronic liver disease. Thus, the modulation of the gut microbiota has attracted research interest as a novel therapeutic approach for the management of NAFLD patients. The modification of microbiota can be achieved by substantial diet modification and the application of probiotics or prebiotics, while the most radical effects are observed by fecal microbiota transplantation (FMT). Given the results of FMT in the context of metabolic syndrome (MetS) and NAFLD in animal models and scarce pilot studies on humans, FMT seems to be a promising treatment option that could reverse intestinal dysbiosis and thereby influence the course of NAFLD.
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Affiliation(s)
- Goran Hauser
- Department of Gastroenterology, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia; (G.H.); (I.K.-Z.); (I.M.)
- Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia;
| | - Indira Benjak Horvat
- Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia;
- County Hospital Varaždin, 42000 Varaždin, Croatia
| | - Mirjana Rajilić-Stojanović
- Department of Biochemical Engineering & Biotechnology, Faculty of Technology and Metallurgy, University of Belgrade, 11000 Belgrade, Serbia;
| | - Irena Krznarić-Zrnić
- Department of Gastroenterology, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia; (G.H.); (I.K.-Z.); (I.M.)
| | - Michail Kukla
- Department of Internal Medicine and Geriatrics, Jagiellonian University Medical College, 31-121 Cracow, Poland;
- Department of Endoscopy, University Hospital in Cracow, 30-688 Cracow, Poland
- 1st Infectious Diseases Ward, Gromkowski Regional Specialist Hospital, Wroclaw, 5 Koszarowa St., 50-149 Wroclaw, Poland
| | - Vedrana Aljinović-Vučić
- Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia;
- Medical Affairs Department, Jadran Galenski Laboratorij d.d., 51000 Rijeka, Croatia
| | - Ivana Mikolašević
- Department of Gastroenterology, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia; (G.H.); (I.K.-Z.); (I.M.)
- Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia;
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Younossi ZM, Kalligeros M, Henry L. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol 2025; 31:S32-S50. [PMID: 39159948 PMCID: PMC11925440 DOI: 10.3350/cmh.2024.0431] [Citation(s) in RCA: 57] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 08/13/2024] [Accepted: 08/15/2024] [Indexed: 08/21/2024] Open
Abstract
As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Currently, 38% of all adults and 7-14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%. Although MASLD does not always develop into progressive liver disease, it has become the top indication for liver transplant in the United States for women and those with hepatocellular carcinoma (HCC). Nonetheless, the most common cause of mortality among patients with MASLD remains cardiovascular disease. In addition to liver outcomes (cirrhosis and HCC), MASLD is associated with an increased risk of developing de novo T2D, chronic kidney disease, sarcopenia, and extrahepatic cancers. Furthermore, MASLD is associated with decreased health-related quality of life, decreased work productivity, fatigue, increased healthcare resource utilization, and a substantial economic burden. Similar to other metabolic diseases, lifestyle interventions such as a heathy diet and increased physical activity remain the cornerstone of managing these patients. Although several obesity and T2D drugs are available to treat co-morbid disease, resmetirom is the only MASH-targeted medication for patients with stage 2-3 fibrosis that has approved by the Food and Drug Administration for use in the United States. This review discusses MASLD epidemiology and its related risk factors and outcomes and demonstrates that without further global initiatives, MASLD incidence could continue to increase.
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Affiliation(s)
- Zobair M. Younossi
- The Global NASH Council, Washington DC, USA
- Beatty Liver and Obesity Program, Inova Health System, Falls Church, VA, USA
- Center for Outcomes Research in Liver Disease, Washington DC, USA
| | - Markos Kalligeros
- Beth Israel Deaconess Medical Center, Harvard University, Cambridge, MA, USA
| | - Linda Henry
- The Global NASH Council, Washington DC, USA
- Beatty Liver and Obesity Program, Inova Health System, Falls Church, VA, USA
- Center for Outcomes Research in Liver Disease, Washington DC, USA
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Liu B, Sun X, Li X, Lu F, Xing G, Ma G, Ran Y, Hu SP. Associations of C-reactive protein to lymphocyte ratio and metabolic-dysfunction-associated steatotic liver disease: evidence from NHANES 2017-2018. BMC Gastroenterol 2024; 24:475. [PMID: 39719591 DOI: 10.1186/s12876-024-03458-7] [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: 07/22/2024] [Accepted: 10/14/2024] [Indexed: 12/26/2024] Open
Abstract
BACKGROUND This study aimed to investigate the association between Metabolic-dysfunction-associated steatotic liver disease(MASLD)and C-reactive protein/lymphocyte ratio (CLR). METHODS MASLD was defined as a Controlled Attenuation Parameter (CAP ≥ 274dB/m) and CLR = C-reactive protein/lymphocyte. A multifactor linear regression model was used to test the relationship between MASLD and CLR. Smoothed curves and threshold effects analyses were fitted to describe nonlinear relationships. Subgroup analyses and interaction tests were then performed according to gender, prevalence of diabetes, ethnicity, and smoking status. RESULTS A total of 1846 participants from the NHANES database were included in this study. In the unadjusted model and model 1 (adjusted for age, sex, and race), CLR was positively associated with MASLD pathogenicity. Unadjusted model (OR = 1.04, 95% CI: 1.02-1.07, P = 0.0017), model 1 (OR = 1.04, 95% CI: 1.01-1.07, P = 0.0056). The results of the fitted smoothed curves showed that CLR and the risk of developing MASLD were nonlinear. Interaction tests and subgroup analyses confirmed that there were no significant interactions between CLR and MASLD causation with gender, race, prevalence of diabetes mellitus, and smoking status(P interaction>0.05). CONCLUSIONS This study shows that CLR is positively associated with the risk of developing MASLD Targeting CLR levels may be a new approach to treating MASLD.
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Affiliation(s)
- Bowen Liu
- Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Long Gang), Shenzhen, Guangdong, China.
| | - Xiaomei Sun
- Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Long Gang), Shenzhen, Guangdong, China.
| | - Xiaobin Li
- Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Long Gang), Shenzhen, Guangdong, China
| | - Fenping Lu
- Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Long Gang), Shenzhen, Guangdong, China
| | - Guangyan Xing
- Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Long Gang), Shenzhen, Guangdong, China
| | - Guiping Ma
- Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Long Gang), Shenzhen, Guangdong, China
| | - Yun Ran
- Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Long Gang), Shenzhen, Guangdong, China
| | - Shi Ping Hu
- Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Long Gang), Shenzhen, Guangdong, China.
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Giangregorio F, Mosconi E, Debellis MG, Provini S, Esposito C, Garolfi M, Oraka S, Kaloudi O, Mustafazade G, Marín-Baselga R, Tung-Chen Y. A Systematic Review of Metabolic Syndrome: Key Correlated Pathologies and Non-Invasive Diagnostic Approaches. J Clin Med 2024; 13:5880. [PMID: 39407941 PMCID: PMC11478146 DOI: 10.3390/jcm13195880] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.
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Affiliation(s)
- Francesco Giangregorio
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Emilio Mosconi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Maria Grazia Debellis
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Stella Provini
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Ciro Esposito
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Matteo Garolfi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Simona Oraka
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Olga Kaloudi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Gunel Mustafazade
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Raquel Marín-Baselga
- Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;
| | - Yale Tung-Chen
- Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;
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Suwała S, Junik R. Assessment of the Liver Steatosis and Fibrosis Risk in Metabolic Syndrome and Its Individual Components, Considering the Varying Definitions Used in Clinical Practice throughout Time: A Retrospective Cross-Sectional Study. Biomedicines 2024; 12:1739. [PMID: 39200204 PMCID: PMC11351204 DOI: 10.3390/biomedicines12081739] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 07/25/2024] [Accepted: 07/31/2024] [Indexed: 09/02/2024] Open
Abstract
Multiple modifications of metabolic syndrome diagnostic criteria have been made-NCEP: ATP III (from 2001, modified in 2004), IDF (2005), IDF Consortium (2009), or Polish Scientific Society Consortium standards (2022) are now frequently in use. Hepatosteatosis and hepatofibrosis are commonly mentioned aspects of metabolic syndrome that greatly increase the likelihood of developing complications. The objective of the study was to assess different diagnostic criteria for metabolic syndrome based on the prevalence of liver steatosis and fibrosis. A retrospective analysis was conducted on the medical data of 2102 patients. Out of all the single criteria, meeting the obesity criterion based on waist circumference showed the highest increase in the risk of hepatosteatosis (by 64-69%, depending on the definition used)-hypertriglyceridemia increased the risk of hepatofibrosis by 71%. Regardless of the specific criteria used, patients with metabolic syndrome had a 34-36% increased likelihood of developing hepatosteatosis-the probability of hepatofibrosis varied between 42% and 47% for the criteria established in 2004, 2005, and 2009, while the Polish 2022 criteria were not statistically significant (p = 0.818). It seems appropriate to establish consistent metabolic syndrome diagnostic criteria-the 2009 IDF guidelines are the most effective in assessing hepatosteatosis and fibrosis risk.
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Affiliation(s)
- Szymon Suwała
- Department of Endocrinology and Diabetology, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland;
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Gordito Soler M, López-González ÁA, Vallejos D, Martínez-Almoyna Rifá E, Vicente-Herrero MT, Ramírez-Manent JI. Usefulness of Body Fat and Visceral Fat Determined by Bioimpedanciometry versus Body Mass Index and Waist Circumference in Predicting Elevated Values of Different Risk Scales for Non-Alcoholic Fatty Liver Disease. Nutrients 2024; 16:2160. [PMID: 38999907 PMCID: PMC11243258 DOI: 10.3390/nu16132160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/28/2024] [Accepted: 07/05/2024] [Indexed: 07/14/2024] Open
Abstract
BACKGROUND Obesity constitutes a public health problem worldwide and causes non-alcoholic fatty liver disease (MALFD), the leading cause of liver disease in developed countries, which progresses to liver cirrhosis and liver cancer. MAFLD is associated with obesity and can be evaluated by validated formulas to assess MAFLD risk using different parameters such as the body mass index (BMI) and waist circumference (WC). However, these parameters do not accurately measure body fat. As MAFLD is strongly associated with obesity, we hypothesize that measuring body and visceral fat by electrical bioimpedance is an efficient method to predict the risk of MAFLD. The objective of our work was to demonstrate that electrical bioimpedance is a more efficient method than the BMI or WC to predict an elevated risk of MAFLD. METHODS A cross-sectional, descriptive study involving 8590 Spanish workers in the Balearic Islands was carried out. The study's sample of employees was drawn from those who underwent occupational medicine examinations between January 2019 and December 2020. Five MAFLD risk scales were determined for evaluating very high levels of body fat and visceral fat. The determination of body and visceral fat was performed using bioimpedanciometry. Student's t-test was employed to ascertain the mean and standard deviation of quantitative data. The chi-square test was used to find prevalences for qualitative variables, while ROC curves were used to define the cut-off points for body and visceral fat. The calculations included the area under the curve (AUC), the cut-off points along with their Youden index, sensitivity, and specificity. Correlation and concordance between the various scales were determined using Pearson's correlation index and Cohen's kappa, respectively. RESULTS As both total body fat and visceral fat increase, the risk of MAFLD increases with a statistically significant result (p < 0.001), presenting a higher risk in men. The areas under the curve (AUC) of the five scales that assess overweight and obesity to determine the occurrence of high values of the different MAFLD risk scales were very high, most of them exceeding 0.9. These AUC values were higher for visceral and body fat than for the BMI or waist circumference. FLD-high presented the best results in men and women with the AUC at around 0.97, both for visceral fat and total body fat, with a high Youden index in all cases (women body fat = 0.830, visceral fat = 0.892; men body fat = 0.780, visceral fat = 0.881). CONCLUSIONS In our study, all the overweight and obesity scales show a very good association with the scales assessing the risk of MAFLD. These values are higher for visceral and body fat than for waist circumference and the BMI. Both visceral fat and body fat are better associated than the BMI and waist circumference with MAFLD risk scales.
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Affiliation(s)
| | - Ángel Arturo López-González
- Investigation Group ADEMA SALUD, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain
- Faculty of Dentistry, University School ADEMA, 07010 Palma, Balearic Islands, Spain
| | - Daniela Vallejos
- Investigation Group ADEMA SALUD, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain
- Faculty of Dentistry, University School ADEMA, 07010 Palma, Balearic Islands, Spain
| | - Emilio Martínez-Almoyna Rifá
- Investigation Group ADEMA SALUD, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain
- Faculty of Dentistry, University School ADEMA, 07010 Palma, Balearic Islands, Spain
| | - María Teófila Vicente-Herrero
- Investigation Group ADEMA SALUD, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain
| | - José Ignacio Ramírez-Manent
- Investigation Group ADEMA SALUD, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain
- Institut d'Investigació Sanitària de les Illes Balears (IDISBA), Balearic Islands Health Research Institute Foundation, 07010 Palma, Balearic Islands, Spain
- Balearic Islands Health Service, 07010 Palma, Balearic Islands, Spain
- Faculty of Medicine, University of the Balearic Islands, 07010 Palma, Balearic Islands, Spain
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Lonardo A, Ballestri S, Mantovani A, Targher G, Bril F. Endpoints in NASH Clinical Trials: Are We Blind in One Eye? Metabolites 2024; 14:40. [PMID: 38248843 PMCID: PMC10820221 DOI: 10.3390/metabo14010040] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 12/31/2023] [Accepted: 01/05/2024] [Indexed: 01/23/2024] Open
Abstract
This narrative review aims to illustrate the notion that nonalcoholic steatohepatitis (NASH), recently renamed metabolic dysfunction-associated steatohepatitis (MASH), is a systemic metabolic disorder featuring both adverse hepatic and extrahepatic outcomes. In recent years, several NASH trials have failed to identify effective pharmacological treatments and, therefore, lifestyle changes are the cornerstone of therapy for NASH. with this context, we analyze the epidemiological burden of NASH and the possible pathogenetic factors involved. These include genetic factors, insulin resistance, lipotoxicity, immuno-thrombosis, oxidative stress, reprogramming of hepatic metabolism, and hypoxia, all of which eventually culminate in low-grade chronic inflammation and increased risk of fibrosis progression. The possible explanations underlying the failure of NASH trials are also accurately examined. We conclude that the high heterogeneity of NASH, resulting from variable genetic backgrounds, exposure, and responses to different metabolic stresses, susceptibility to hepatocyte lipotoxicity, and differences in repair-response, calls for personalized medicine approaches involving research on noninvasive biomarkers. Future NASH trials should aim at achieving a complete assessment of systemic determinants, modifiers, and correlates of NASH, thus adopting a more holistic and unbiased approach, notably including cardiovascular-kidney-metabolic outcomes, without restricting therapeutic perspectives to histological surrogates of liver-related outcomes alone.
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Affiliation(s)
- Amedeo Lonardo
- AOU—Modena—Ospedale Civile di Baggiovara, 41126 Modena, Italy;
| | | | - Alessandro Mantovani
- Section of Endocrinology and Diabetes, Department of Medicine, University of Verona, Piazzale Stefani, 37126 Verona, Italy
| | - Giovanni Targher
- Department of Medicine, University of Verona, 37126 Verona, Italy;
- Metabolic Diseases Research Unit, IRCCS Sacro Cuore—Don Calabria Hospital, 37024 Negrar di Valpolicella, Italy
| | - Fernando Bril
- Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35233, USA;
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Chaudhury T, Brodosi L, Marchesini G, Mitra SK, Petroni ML. NAFLD, the hepatic manifestation of the metabolic syndrome. METABOLIC SYNDROME 2024:279-291. [DOI: 10.1016/b978-0-323-85732-1.00055-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Effenberger M, Grander C, Grabherr F, Tilg H. Nonalcoholic Fatty Liver Disease and the Intestinal Microbiome: An Inseparable Link. J Clin Transl Hepatol 2023; 11:1498-1507. [PMID: 38161503 PMCID: PMC10752805 DOI: 10.14218/jcth.2023.00069] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 04/21/2023] [Accepted: 07/18/2023] [Indexed: 01/03/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) particularly affects patients with type 2 diabetes and obesity. The incidence of NAFLD has increased significantly over the last decades and is now pandemically across the globe. It is a complex systemic disease comprising hepatic lipid accumulation, inflammation, lipotoxicity, gut dysbiosis, and insulin resistance as main features and with the potential to progress to cirrhosis and hepatocellular carcinoma (HCC). In numerous animal and human studies the gut microbiota plays a key role in the pathogenesis of NAFLD, NAFLD-cirrhosis and NAFLD-associated HCC. Lipotoxicity is the driver of inflammation, insulin resistance, and liver injury. Likewise, western diet, obesity, and metabolic disorders may alter the gut microbiota, which activates innate and adaptive immune responses and fuels hereby hepatic and systemic inflammation. Indigestible carbohydrates are fermented by the gut microbiota to produce important metabolites, such as short-chain fatty acids and succinate. Numerous animal and human studies suggested a pivotal role of these metabolites in the progression of NAFLD and its comorbidities. Though, modification of the gut microbiota and/or the metabolites could even be beneficial in patients with NAFLD, NAFLD-cirrhosis, and NAFLD-associated HCC. In this review we collect the evidence that exogenous and endogenous hits drive liver injury in NAFLD and propel liver fibrosis and the progressing to advanced disease stages. NAFLD can be seen as the product of a complex interplay between gut microbiota, the immune response and metabolism. Thus, the challenge will be to understand its pathogenesis and to develop new therapeutic strategies.
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Affiliation(s)
- Maria Effenberger
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Christoph Grander
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Felix Grabherr
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
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Nagai K, Nagai K, Iwaki M, Kobayashi T, Nogami A, Oka M, Saito S, Yoneda M. Frontiers of Collaboration between Primary Care and Specialists in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Review. Life (Basel) 2023; 13:2144. [PMID: 38004284 PMCID: PMC10672694 DOI: 10.3390/life13112144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 10/27/2023] [Accepted: 10/29/2023] [Indexed: 11/26/2023] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common liver disease. It has a rapidly growing patient population owing to the increasing prevalence of obesity and type 2 diabetes. Patients with MASLD are primarily treated by family physicians when fibrosis is absent or mild and by gastroenterologists/hepatologists when fibrosis is more advanced. It is imperative that a system for the appropriate treatment and surveillance of hepatocellular carcinoma be established in order to ensure that highly fibrotic cases are not overlooked among the large number of MASLD patients. Family physicians should check for viral hepatitis, autoimmune hepatitis, alcoholic liver disease, and drug-induced liver disease, and should evaluate fibrosis using NIT; gastroenterologists/hepatologists should perform liver biopsy, ultrasound elastography (260 units in Japan as of October 2023), and MR elastography (35 units in Japan as of October 2023). This review presents the latest findings in MASLD and the role, accuracy, and clinical use of NIT. It also describes the collaboration between Japanese primary care and gastroenterologists/hepatologists in Japan in the treatment of liver diseases, including MASLD.
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Affiliation(s)
- Koki Nagai
- Gastroenterology Division, National Hospital Organization Yokohama Medical Center, 3-60-2 Harajyuku, Totsuka-ku, Yokohama 245-8575, Japan;
| | - Kazuki Nagai
- Nagai Clinic, 1-7-25 Yokodai, Isogo-ku, Yokohama 235-0045, Japan;
| | - Michihiro Iwaki
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan; (M.I.); (T.K.); (A.N.)
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan; (M.I.); (T.K.); (A.N.)
| | - Asako Nogami
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan; (M.I.); (T.K.); (A.N.)
| | - Masanao Oka
- OkaMedical, 1-19-18-3F Kamiookanishi, Kounan-ku, Yokohama 233-0002, Japan;
| | - Satoru Saito
- Sanno Hospital, 8-10-16 Akasaka, Minato-ku, Tokyo 107-0052, Japan;
| | - Masato Yoneda
- Gastroenterology Division, National Hospital Organization Yokohama Medical Center, 3-60-2 Harajyuku, Totsuka-ku, Yokohama 245-8575, Japan;
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Ramírez-Mejía MM, Méndez-Sánchez N. What Is in a Name: from NAFLD to MAFLD and MASLD—Unraveling the Complexities and Implications. CURRENT HEPATOLOGY REPORTS 2023; 22:221-227. [DOI: 10.1007/s11901-023-00620-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/11/2023] [Indexed: 01/03/2025]
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12
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Understanding NAFLD: From Case Identification to Interventions, Outcomes, and Future Perspectives. Nutrients 2023; 15:nu15030687. [PMID: 36771394 PMCID: PMC9921401 DOI: 10.3390/nu15030687] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 01/25/2023] [Accepted: 01/28/2023] [Indexed: 02/01/2023] Open
Abstract
While non-alcoholic fatty liver disease (NAFLD) is a prevalent and frequent cause of liver-related morbidity and mortality, it is also strongly associated with cardiovascular disease-related morbidity and mortality, likely driven by its associations with insulin resistance and other manifestations of metabolic dysregulation. However, few satisfactory pharmacological treatments are available for NAFLD due in part to its complex pathophysiology, and challenges remain in stratifying individual patient's risk for liver and cardiovascular disease related outcomes. In this review, we describe the development and progression of NAFLD, including its pathophysiology and outcomes. We also describe different tools for identifying patients with NAFLD who are most at risk of liver-related and cardiovascular-related complications, as well as current and emerging treatment options, and future directions for research.
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13
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Prieto Ortíz JE, Sánchez Luque CB, Ortega Quiróz RJ. Hígado graso (parte 1): aspectos generales, epidemiología, fisiopatología e historia natural. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2022; 37:420-433. [DOI: 10.22516/25007440.952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
El hígado graso no alcohólico (NAFLD) se define por la presencia de grasa o esteatosis en los hepatocitos y abarca un espectro que va desde la esteatosis simple, pasa por la esteatohepatitis no alcohólica (NASH) con inflamación y fibrosis, y finaliza en la cirrosis. Se considera una prevalencia mundial global cercana al 25% en la población general y se diagnóstica entre los 40 y 50 años, con variaciones respecto al sexo predominante y con diferencias étnicas (la población hispana es la más afectada). El hígado graso está asociado al síndrome metabólico (SM), y la obesidad se considera el principal factor de riesgo con su presencia y con su progresión.
El hígado graso es un trastorno complejo y muy heterogéneo en su fisiopatología, que resulta de la interacción de múltiples elementos: factores genéticos, epigenéticos, ambientales, culturales, entre otros. Todo ello en conjunto lleva a incremento paulatino de grasa hepática, resistencia a la insulina y alteraciones hormonales y de la microbiota intestinal, lo que genera un daño hepatocelular a través de la formación de radicales libres de oxígeno y activación de la fibrogénesis hepática.
La historia natural del hígado graso es dinámica: los pacientes con esteatosis simple tienen bajo riesgo de progresión a cirrosis, mientras que en los pacientes con NASH este riesgo se aumenta; sin embargo, el proceso puede ser reversible y algunas personas tendrán una mejoría espontánea. La fibrosis parece ser el determinante de la mortalidad global y de los desenlaces asociados a la enfermedad hepática; se considera que en todos los pacientes la fibrosis empeora una etapa cada 14 años y en NASH empeora en una etapa cada 7 años. Estudios previos concluyen que aproximadamente 20% de los casos de esteatosis simple progresan a NASH y que, de ellos, aproximadamente el 20% progresan a cirrosis, con presencia de hepatocarcinoma (HCC) en el 5% a 10% de ellos.
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14
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Malnick SDH, Alin P, Somin M, Neuman MG. Fatty Liver Disease-Alcoholic and Non-Alcoholic: Similar but Different. Int J Mol Sci 2022; 23:16226. [PMID: 36555867 PMCID: PMC9783455 DOI: 10.3390/ijms232416226] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 12/12/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022] Open
Abstract
In alcohol-induced liver disease (ALD) and in non-alcoholic fatty liver disease (NAFLD), there are abnormal accumulations of fat in the liver. This phenomenon may be related to excessive alcohol consumption, as well as the combination of alcohol consumption and medications. There is an evolution from simple steatosis to steatohepatitis, fibrosis and cirrhosis leading to hepatocellular carcinoma (HCC). Hepatic pathology is very similar regarding non-alcoholic fatty liver disease (NAFLD) and ALD. Initially, there is lipid accumulation in parenchyma and progression to lobular inflammation. The morphological changes in the liver mitochondria, perivenular and perisinusoidal fibrosis, and hepatocellular ballooning, apoptosis and necrosis and accumulation of fibrosis may lead to the development of cirrhosis and HCC. Medical history of ethanol consumption, laboratory markers of chronic ethanol intake, AST/ALT ratio on the one hand and features of the metabolic syndrome on the other hand, may help in estimating the contribution of alcohol intake and the metabolic syndrome, respectively, to liver steatosis.
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Affiliation(s)
- Stephen D. H. Malnick
- Department of Internal Medicine, Kaplan Medical Center, Affiliated to Hebrew University, Rehovot 76100, Israel
| | - Pavel Alin
- Department of Internal Medicine, Kaplan Medical Center, Affiliated to Hebrew University, Rehovot 76100, Israel
| | - Marina Somin
- Department of Internal Medicine, Kaplan Medical Center, Affiliated to Hebrew University, Rehovot 76100, Israel
| | - Manuela G. Neuman
- In Vitro Drug Safety and Biotechnology, Department of Pharmacology and Toxicology, Temerity Faculty of Medicine, University of Toronto, Toronto, ON M5G OA3, Canada
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15
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Lyu J, Lin Q, Fang Z, Xu Z, Liu Z. Complex impacts of gallstone disease on metabolic syndrome and nonalcoholic fatty liver disease. Front Endocrinol (Lausanne) 2022; 13:1032557. [PMID: 36506064 PMCID: PMC9727379 DOI: 10.3389/fendo.2022.1032557] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 10/25/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Patients with gallstone disease (GSD) often have highly co-occurrence with metabolic syndrome (MetS) and Nonalcoholic fatty liver disease (NAFLD) both associated with insulin resistance (IR). Meanwhile, highly prevalence of NAFLD was found in patients who received cholecystectomy. However, the associations of GSD with MetS, NAFLD is inconsistent in the published literature. And risk of cholecystectomy on NAFLD is unclear. METHODS We searched the Medline EMBASE and WOS databases for literature that met our study topic. To be specific, studies with focus on associations between GSD and MetS/NAFLD, and risk evaluation on cholecystectomy and NAFLD incidence were enrolled for further analysis. The random effect model was used to calculate the combined relative ratio (RR) and odds ratio (OR)and 95% confidence interval (CI). RESULTS Seven and six papers with focus on connections between GSD and NAFLD/MetS prevalence. Correspondingly, seven papers with focus on risk of cholecystectomy on NAFLD occurrence were also enrolled into meta-analysis. After pooling the results from individual study, patients with GSD had higher risk of MetS (OR:1.45, 95%CI: 1.23-1.67, I2 = 41.1%, P=0.165). Risk of GSD was increased by 52% in NAFLD patients (pooled OR:1.52, 95%CI:1.24-1.80). And about 32% of increment on NAFLD prevalence was observed in patients with GSD (pooled OR: 1.32, 95%CI:1.14-1.50). With regard to individual MetS components, patients with higher systolic blood pressure were more prone to develop GSD, with combined SMD of 0.29 (96%CI: 0.24-0.34, P<0.05). Dose-response analysis found the GSD incidence was significantly associated with increased body mass index (BMI) (pooled OR: 1.02, 95%CI:1.01-1.03) in linear trends. Patients who received cholecystectomy had a higher risk of post-operative NAFLD (OR:2.14, 95%CI: 1.43-2.85), P<0.05). And this impact was amplified in obese patients (OR: 2.51, 95%CI: 1.95-3.06, P<0.05). CONCLUSION Our results confirmed that controls on weight and blood pressure might be candidate therapeutic strategy for GSD prevention. And concerns should be raised on de-novo NAFLD after cholecystectomy.
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Affiliation(s)
- Jingting Lyu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, China
| | - Qinghong Lin
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, China
| | - Zhongbiao Fang
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, China
| | - Zeling Xu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, China
| | - Zhengtao Liu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, China
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- Shulan (Hangzhou) Hospital, Hangzhou, China
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16
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Zeina AR, Kopelman Y, Mari A, Ahmad HS, Artul S, Khalaila AS, Taher R, Villannueva FZ, Safadi R, Abu Mouch S, Abu Baker F. Pulmonary embolism risk in hospitalized patients with nonalcoholic fatty liver disease: A case-control study. Medicine (Baltimore) 2022; 101:e31710. [PMID: 36397431 PMCID: PMC9666162 DOI: 10.1097/md.0000000000031710] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 10/18/2022] [Indexed: 11/19/2022] Open
Abstract
Abundant research has associated nonalcoholic fatty liver disease (NAFLD) with atherosclerosis, but very few reports have evaluated the association between NAFLD and venous thromboembolism. We aimed to investigate the association between NAFLD and pulmonary embolism (PE) in hospitalized patients. In this retrospective case-control study, we included consecutive patients from 2 university-affiliated hospitals who were referred for CT pulmonary angiograms for a suspected PE. Patients with a history of excessive alcohol consumption, chronic liver diseases or cirrhosis were excluded. The imaging studies of the entire cohort were reviewed by 2 expert radiologists who confirmed the diagnosis of PE and examined the liver to detect and grade hepatic steatosis. Accordingly, patients were categorized into NAFLD patients and non-NAFLD controls. Patient demographics, medical history, hospitalization details as well as patients' outcomes were documented. Multivariate analysis was performed to identify predictors for developing PE and hazard ratios with corresponding 95% confidence intervals were estimated. A total of 377 patients (101 with NAFLD and 276 controls) were included. NAFLD patients had significantly higher BMI values (33.16 ± 6.78 vs 26.81 ± 5.6; P < .001) and prevalence of diabetes (41 (40%) vs 85 (30.8%); P = .03). The prevalence of PE was significantly higher in the NAFLD group (80 (79.2%) vs 147 (53.3%), P < .001). In a multivariate analysis, older age, recent surgery or trauma, active malignancy, smoking, and NAFLD (HR ratio = 4.339, P < .0001 and 95% CI = 2.196-8.572) were independently associated with PE development. Patients with NAFLD were associated with an increased risk of developing PE independent of other classical risk factors for PE.
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Affiliation(s)
- Abdel-Rauf Zeina
- Department of Radiology, Hillel Yaffe Medical Center, Hadera, Israel
| | - Yael Kopelman
- Department of Gastroenterology and Hepatology, Hillel Yaffe Medical Center, Hadera, Israel
| | - Amir Mari
- Department of Gastroenterology, Nazareth EMMS Hospital, Nazareth, Israel
| | - Helal Said Ahmad
- Department of Gastroenterology, Nazareth EMMS Hospital, Nazareth, Israel
| | - Suheil Artul
- Department of Radiology, Nazareth EMMS Hospital, Nazareth, Israel
| | | | - Randa Taher
- Department of Internal Medicine, Hillel Yaffe Medical Center, Hadera, Israel
| | | | - Rabea Safadi
- Department of Radiology, Hillel Yaffe Medical Center, Hadera, Israel
| | - Saif Abu Mouch
- Department of Internal Medicine, Hillel Yaffe Medical Center, Hadera, Israel
| | - Fadi Abu Baker
- Department of Gastroenterology and Hepatology, Hillel Yaffe Medical Center, Hadera, Israel
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17
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Basu R, Noureddin M, Clark JM. Nonalcoholic Fatty Liver Disease: Review of Management for Primary Care Providers. Mayo Clin Proc 2022; 97:1700-1716. [PMID: 36058582 DOI: 10.1016/j.mayocp.2022.04.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 03/03/2022] [Accepted: 04/19/2022] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in the United States and worldwide. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), is a leading indication for liver transplant. Comorbidities associated with NAFLD development and NASH include type 2 diabetes, obesity, metabolic syndrome, and dyslipidemia. Extrahepatic morbidity and mortality are considerable as NAFLD is associated with an increased risk of cardiovascular disease and chronic kidney disease. Once NAFLD is diagnosed, the presence of liver fibrosis is the central determinant of hepatic prognosis. Severe liver fibrosis requires aggressive clinical management. No pharmacologic agents have regulatory approval in the United States for the treatment of NAFLD or NASH. Management is centered on efforts to reduce underlying obesity (lifestyle, medications, surgical or endoscopic interventions) and metabolic derangements (prediabetes, type 2 diabetes, hypertension, hyperlipidemia, and others). Current pharmacologic therapy for NAFLD is limited mainly to the use of vitamin E and pioglitazone, although other agents are being investigated in clinical trials. Cardiovascular and metabolic risk factors must also be assessed and managed. Here, NAFLD evaluation, diagnosis, and management are considered in the primary care setting and endocrinology clinics.
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Affiliation(s)
- Rita Basu
- Division of Endocrinology, Department of Medicine, Center of Diabetes Technology, University of Virginia School of Medicine, Charlottesville, VA.
| | - Mazen Noureddin
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Jeanne M Clark
- Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD
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18
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Salgado Alvarez GA, Pinto Galvez SM, Garcia Mora U, Cano Contreras AD, Durán Rosas C, Priego-Parra BA, Triana Romero A, Amieva Balmori M, Roesch Dietlen F, Martinez Vazquez SE, Mendez Guerrero IO, Chi-Cervera LA, Bernal Reyes R, Martinez Roriguez LA, Icaza Chavez ME, Remes Troche JM. Higher cardiovascular risk scores and liver fibrosis risk estimated by biomarkers in patients with metabolic-dysfunction-associated fatty liver disease. World J Hepatol 2022; 14:1633-1642. [PMID: 36157869 PMCID: PMC9453468 DOI: 10.4254/wjh.v14.i8.1633] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/15/2022] [Accepted: 08/01/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The definition of metabolic-dysfunction-associated fatty liver disease (MAFLD) allows identification of metabolically complicated patients. Fibrosis risk scores are related to cardiovascular risk (CVR) scores and could be useful for the identification of patients at risk of systemic complications. AIM To evaluate the relationship between MAFLD and CVR using the Framingham risk score in a group of Mexican patients. METHODS Cross-sectional, observational and descriptive study carried out in a cohort of 585 volunteers in the state of Veracruz with MAFLD criteria. The risk of liver fibrosis was calculated with aspartate aminotransferase-to-platelet ratio index, nonalcoholic fatty liver disease score and fibrosis-4, as well as with transient hepatic elastography with Fibroscan®. The CVR was determined by the Framingham system. RESULTS One hundred and twenty-five participants (21.4%) with MAFLD criteria were evaluated, average age 54.4 years, 63.2% were women, body mass index 32.3 kg/m2. The Framingham CVR was high in 43 patients (33.9%). Transient elastography was performed in 55.2% of volunteers; 39.1% with high CVR and predominance in advanced fibrosis (F3-F4). The logistic regression analysis showed that liver fibrosis, diabetes and hypertension independently increased CVR. CONCLUSION One of every three patients with MAFLD had a high CVR, and in those with high fibrosis risk, the CVR risk was even greater.
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Affiliation(s)
| | | | - Uriel Garcia Mora
- Instituto de Investigaciones Médico-biologicas, Universidad Veracruzana, Veracruz 91700, Veracruz, Mexico
| | - Ana Delfina Cano Contreras
- Instituto de Investigaciones Médico-biologicas, Universidad Veracruzana, Veracruz 91700, Veracruz, Mexico.
| | - Cristina Durán Rosas
- Instituto de Investigaciones Médico-biologicas, Universidad Veracruzana, Veracruz 91700, Veracruz, Mexico
| | - Bryan Adrián Priego-Parra
- Instituto de Investigaciones Médico-biologicas, Universidad Veracruzana, Veracruz 91700, Veracruz, Mexico
| | - Arturo Triana Romero
- Instituto de Investigaciones Médico-biologicas, Universidad Veracruzana, Veracruz 91700, Veracruz, Mexico
| | - Mercedes Amieva Balmori
- Instituto de Investigaciones Médico-biologicas, Universidad Veracruzana, Veracruz 91700, Veracruz, Mexico
| | - Federico Roesch Dietlen
- Instituto de Investigaciones Médico-biologicas, Universidad Veracruzana, Veracruz 91700, Veracruz, Mexico
| | - Sophia Eugenia Martinez Vazquez
- Department of Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México 14080, México, Mexico
| | - Ines Osvely Mendez Guerrero
- Department of Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México 14080, México, Mexico
| | - Luis Alberto Chi-Cervera
- Clínica de Especialidades Gastrointestinales y Hepáticas, Hospital Star Medica, Merida 97133, Yucatan, Mexico
| | - Raúl Bernal Reyes
- Department of Gastroenterologia, Sociedad Española de Beneficencia, Pachuca 42000, Hidalgo, Mexico
| | | | | | - Jose Maria Remes Troche
- Instituto de Investigaciones Médico-biologicas, Universidad Veracruzana, Veracruz 91700, Veracruz, Mexico
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19
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Clinical Progression of Metabolic-Associated Fatty Liver Disease Is Rare in a Danish Tertiary Liver Center. J Clin Med 2022; 11:jcm11092271. [PMID: 35566397 PMCID: PMC9104099 DOI: 10.3390/jcm11092271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/13/2022] [Accepted: 04/14/2022] [Indexed: 11/22/2022] Open
Abstract
Data concerning non-invasive discrimination of simple steatosis from steatohepatitis in metabolic-associated fatty liver disease (MAFLD) and risk of disease progression in patients with MAFLD are conflicting. We aimed to investigate these factors in an MAFLD cohort at a Danish tertiary liver centre. We retrospectively assessed 129 patients with biopsy-proven MAFLD. Patients were divided according to the presence of simple steatosis or steatohepatitis in liver biopsies. Histological and clinical progression were assessed during follow-up. Patients with steatohepatitis had higher BMIs, liver stiffness, HbA1c and soluble (sCD163) and were more prone to have metabolic syndrome at baseline compared with simple steatosis patients. Of the 129 patients, 31 had a follow-up biopsy after a median of 287 days; simple steatosis progressed to steatohepatitis in 7 cases, while 2 regressed. Twenty patients had the same fibrosis stage according to the follow-up biopsy, seven progressed and four regressed. Only 14 patients progressed clinically (median follow-up time was 3.8 years). Clinical progression was associated with female sex, high creatinine, high sCD163 and disease severity in the diagnostic liver biopsy. Steatohepatitis was associated with metabolic and inflammatory parameters including fibroscan. Disease progression was seen in only 11% of cases and was mainly related to more severe histological disease at baseline.
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20
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Wang TY, Wang RF, Bu ZY, Targher G, Byrne CD, Sun DQ, Zheng MH. Association of metabolic dysfunction-associated fatty liver disease with kidney disease. Nat Rev Nephrol 2022; 18:259-268. [PMID: 35013596 DOI: 10.1038/s41581-021-00519-y] [Citation(s) in RCA: 126] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2021] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in more than 5% of hepatocytes in the absence of excessive alcohol consumption and other secondary causes of hepatic steatosis. In 2020, the more inclusive term metabolic (dysfunction)-associated fatty liver disease (MAFLD) - defined by broader diagnostic criteria - was proposed to replace the term NAFLD. The new terminology and revised definition better emphasize the pathogenic role of metabolic dysfunction and uses a set of definitive, inclusive criteria for diagnosis. Diagnosis of MAFLD is based on evidence of hepatic steatosis (as assessed by liver biopsy, imaging techniques or blood biomarkers and scores) in persons who are overweight or obese and have type 2 diabetes mellitus or metabolic dysregulation, regardless of the coexistence of other liver diseases or excessive alcohol consumption. The known association between NAFLD and chronic kidney disease (CKD) and our understanding that CKD can occur as a consequence of metabolic dysfunction suggests that individuals with MAFLD - who by definition have fatty liver and metabolic comorbidities - are at increased risk of CKD. In this Perspective article, we discuss the clinical associations between MAFLD and CKD, the pathophysiological mechanisms by which MAFLD may increase the risk of CKD and the potential drug treatments that may benefit both conditions.
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Affiliation(s)
- Ting-Yao Wang
- Department of Nephrology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Rui-Fang Wang
- Department of Nephrology, the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Zhi-Ying Bu
- Department of Nephrology, the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Christopher D Byrne
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Dan-Qin Sun
- Department of Nephrology, the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China.
- Affiliated Wuxi Clinical College of Nantong University, Wuxi, China.
| | - Ming-Hua Zheng
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China.
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21
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Gangireddy VGR, Pilkerton C, Xiang J, Tinajero R, Ashcraft AM. Hepatic Fibrosis and Steatosis in Metabolic Syndrome. J Obes Metab Syndr 2022; 31:61-69. [PMID: 35283365 PMCID: PMC8987451 DOI: 10.7570/jomes21062] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 11/29/2021] [Accepted: 12/12/2021] [Indexed: 12/13/2022] Open
Abstract
Background Metabolic syndrome (MetS) is a group of factors associated with increased risks of cardiovascular disease and overall mortality. Nonalcoholic fatty liver disease (NAFLD) is a common disorder that has been shown to cause hepatic steatosis and fibrosis. The relationship between NAFLD and MetS appears to be bidirectional, but very few studies have examined the role of MetS in hepatic steatosis and fibrosis. The present study investigated the relationships between MetS and its components and the severity of hepatic fibrosis and steatosis, and fibrosis independent of steatosis. Methods The study was a cross-sectional population-based survey of 4,678 National Health and Nutrition Examination Survey participants from 2017 to 2018 in the United States. Hepatic fibrosis and steatosis were measured using liver elastography. The MetS components were assessed using demographic, examination, laboratory, and self-reported data. Results Using survey-weighted population estimates, 26% of the population had steatosis, 7.5% had fibrosis, and 3.3% had fibrosis without steatosis. The adjusted odds ratio for any level of steatosis was 4.12 times higher (95% confidence interval [CI], 3.16-5.37) and any level of fibrosis was 3.34 times higher (95% CI, 2.26-4.94) among participants with MetS than those without. The adjusted odds ratio for fibrosis without steatosis is 2.67 times higher (95% CI, 1.47-4.87) among participants with MetS than those without. Conclusion The presence of MetS significantly increases the risk of hepatic fibrosis and steatosis, providing evidence for MetS to be considered an additional independent risk factor for hepatic fibrosis together with other known etiologies.
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Affiliation(s)
| | - Courtney Pilkerton
- Department of Family Medicine, West Virginia University, Morgantown, WV, USA
| | - Jun Xiang
- Department of Family Medicine, West Virginia University, Morgantown, WV, USA
| | - Ruben Tinajero
- Department of Family Medicine, West Virginia University, Morgantown, WV, USA
| | - Amie M Ashcraft
- Department of Family Medicine, West Virginia University, Morgantown, WV, USA
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Baldini F, Khalil M, Serale N, Voci A, Portincasa P, Vergani L. Extent and features of liver steatosis in vitro pave the way to endothelial dysfunction without physical cell-to-cell contact. Nutr Metab Cardiovasc Dis 2021; 31:3522-3532. [PMID: 34629256 DOI: 10.1016/j.numecd.2021.08.032] [Citation(s) in RCA: 1] [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: 01/29/2021] [Revised: 07/09/2021] [Accepted: 08/04/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Several chronic multifactorial diseases originate from energy unbalance between food intake and body energy expenditure, including non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiovascular disorders. Vascular endothelium plays a central role in body homeostasis, and NAFLD is often associated with endothelial dysfunction (ED), the first step in atherosclerosis. Both sugars and fatty acids (FAs) are fuel sources for energy production, but their excess leads to liver steatosis which may trigger ED through a network of mechanisms which need to be clarified. Here, we investigated the crosstalk pathways between in vitro cultured steatotic hepatocytes (FaO) and endothelial cells (HECV) being mediated by soluble factors. METHODS AND RESULTS We employed the conditioned medium approach to test how different extent and features of hepatic steatosis distinctively affect endothelium leading to ED. The steatogenic media collected from steatotic hepatocytes were characterized by high triglyceride content and led to lipid accumulation and fat-dependent dysfunction in HECV cells. We found a parallelism between (i) extent of hepatocyte steatosis and level of lipid accumulation in HECV cells; (ii) type of hepatocyte steatosis (with macro- or microvesicular LDs) and extent of oxidative stress, lipid peroxidation, nitric oxide release and expression of ED markers in HECV cells. CONCLUSIONS The present findings seem to suggest that, in addition to triglycerides, other soluble mediators should be released by steatotic hepatocytes and may influence lipid accumulation and function of HECV cells. Further studies need to depict the exact profile of soluble factors involved in steatotic hepatocyte-endothelium crosstalk.
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Affiliation(s)
- Francesca Baldini
- Department of Earth, Environment and Life Sciences (DISTAV), University of Genova, Corso Europa 26, 16132, Italy; Nanoscopy and NIC@IIT, Istituto Italiano di Tecnologia, Genoa, Italy
| | - Mohamad Khalil
- Clinica Medica "A. Murri", Dept. of Biomedical Sciences and Human Oncology, Medical School, University of Bari "Aldo Moro", Italy
| | - Nadia Serale
- Department of Earth, Environment and Life Sciences (DISTAV), University of Genova, Corso Europa 26, 16132, Italy; Clinica Medica "A. Murri", Dept. of Biomedical Sciences and Human Oncology, Medical School, University of Bari "Aldo Moro", Italy
| | - Adriana Voci
- Department of Earth, Environment and Life Sciences (DISTAV), University of Genova, Corso Europa 26, 16132, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Dept. of Biomedical Sciences and Human Oncology, Medical School, University of Bari "Aldo Moro", Italy
| | - Laura Vergani
- Department of Earth, Environment and Life Sciences (DISTAV), University of Genova, Corso Europa 26, 16132, Italy.
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Niu H, Zhou Y. Nonlinear Relationship Between AST-to-ALT Ratio and the Incidence of Type 2 Diabetes Mellitus: A Follow-Up Study. Int J Gen Med 2021; 14:8373-8382. [PMID: 34819745 PMCID: PMC8608244 DOI: 10.2147/ijgm.s341790] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/05/2021] [Indexed: 12/15/2022] Open
Abstract
Background The aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio has been demonstrated to be associated with insulin resistance and metabolic syndrome. However, few studies have directly explored the association between the AST/ALT ratio and the incidence of type 2 diabetes mellitus (T2DM). As such, the present study aimed to investigate the relationship between the AST/ALT ratio and incident T2DM during follow-up in a population-based cohort. Methods This retrospective cohort analysis included 15,464 Japanese males and females without DM at baseline between 2004 and 2015. The association between AST/ALT ratio and T2DM was retrospectively examined using the Cox proportional hazard model after adjusting for multiple potential confounders. Results After follow-up, 373 (2.41%) patients developed T2DM. A nonlinear relationship between the AST/ALT ratio and T2DM was observed after adjusting for potential confounders. The risk for developing T2DM decreased with AST/ALT ratio up to a threshold of 0.93 (adjusted hazard ratio [HR] 0.14 [95% confidence interval (CI) = 0.02-0.90; P = 0.0385]). An AST/ALT ratio >0.93 was not associated with the risk for developing T2DM (adjusted HR = 0.67, 95% CI = 0.17-2.65; P = 0.5718). Conclusion The AST/ALT ratio was associated with a lower incidence of T2DM in a nonlinear pattern. The threshold AST/ALT ratio for developing T2DM was 0.93. AST/ALT levels were inversely correlated with the occurrence of T2DM when AST/ALT ratio ≤0.93.
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Affiliation(s)
- Hua Niu
- Department of Ultrasound Medicine, Xidian Group Hospital, Xi'an, 710077, People's Republic of China
| | - Yinghua Zhou
- Department of Ultrasound Medicine, Xi'an Gaoxin Hospital, Xi'an, 710075, People's Republic of China
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Baratta F, Ferro D, Pastori D, Colantoni A, Cocomello N, Coronati M, Angelico F, Del Ben M. Open Issues in the Transition from NAFLD to MAFLD: The Experience of the Plinio Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:8993. [PMID: 34501590 PMCID: PMC8430687 DOI: 10.3390/ijerph18178993] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/19/2021] [Accepted: 08/23/2021] [Indexed: 12/15/2022]
Abstract
Metabolic associated fatty liver diseases (MAFLD) definition was proposed to identify fatty liver condition associated to metabolic disorders and to replace non-alcoholic fatty liver disease (NAFLD). We aimed to explore the effect of the application of the new MAFLD criteria on a pre-existing cohort of NAFLD patients. The consequences of the reclassification were investigated by applying the MAFLD criteria to a prospective cohort (The Plinio Study) of dysmetabolic patients examined for the presence of NAFLD. In the Plinio cohort, 795 patients had NAFLD and 767 of them (96.5%) were reclassified as MAFLD patients. Out of these, 94.9% had overweight/obesity or diabetes, while the remaining were lean and had metabolic dysregulation defined by the presence of at least two metabolic risk abnormalities. By contrast, 3.5% of the NAFLD patients were reclassified as no-MAFLD due to the absence of overweight/obesity, diabetes, or metabolic risk abnormalities. The only significant difference between the NAFLD and MAFLD groups was the higher prevalence of subjects with BMI ≥ 25 kg/m2 in the latter (88.6% vs. 92%; p = 0.018). In the cohort, 68 subjects were defined as "lean NAFLD". Of these, 40 were reclassified as MAFLD and 28 as no-MAFLD. In conclusion, when applying MAFLD criteria to the Plinio cohort, there is a substantial overlap between NAFLD and MAFLD diagnosis. However, some specific subgroups of patients, such as those currently defined as lean NAFLD, were excluded by the new MAFLD definition.
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Affiliation(s)
- Francesco Baratta
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Domenico Ferro
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Daniele Pastori
- Emergency Medicine Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy
| | - Alessandra Colantoni
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Nicholas Cocomello
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Mattia Coronati
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Francesco Angelico
- Department of Public Health and Infectious Diseases, Sapienza University, 00161 Rome, Italy;
| | - Maria Del Ben
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
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Differences among Three Skeletal Muscle Mass Indices in Predicting Non-Alcoholic Fatty Liver Disease: Korean Nationwide Population-Based Study. Life (Basel) 2021; 11:life11080751. [PMID: 34440495 PMCID: PMC8401633 DOI: 10.3390/life11080751] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/16/2021] [Accepted: 07/25/2021] [Indexed: 02/06/2023] Open
Abstract
Recent studies have investigated the relationship between sarcopenia and non-alcoholic fatty liver disease (NAFLD); however, there is no unified definition of sarcopenia. Thus, we aimed to investigate the differences among three skeletal muscle mass indices (SMI) in predicting NAFLD. This study included 8133 adults from the 2008–2010 Korea National Health and Nutrition Survey. SMI was calculated as appendicular skeletal muscle mass divided by height-square (hSMI), weight (wSMI), or body mass index (bSMI). The presence of NAFLD was defined by using the NAFLD-liver fat score. On the receiver operating characteristic curve analysis, the predictive power of wSMI for NAFLD was significantly higher than those of hSMI and bSMI in men (wSMI vs. hSMI, p = 0.003; wSMI vs. bSMI, p < 0.001). In women, the predictive power of hSMI was only significantly higher than that of bSMI (p = 0.023), and other predictive powers were not significantly different. In addition, hSMI was correlated with insulin resistance and NAFLD-liver fat score in the opposite direction to wSMI and bSMI in both men and women. Among the three definitions of SMI, wSMI showed the highest diagnostic performance for predicting NAFLD in men, suggesting the importance of defining sarcopenia for its association with specific diseases.
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Clinical Impact of Antecedent Bariatric Surgery on Liver Transplant Outcomes: A Retrospective Matched Case-control Study. Transplantation 2021; 105:1280-1284. [PMID: 32590608 DOI: 10.1097/tp.0000000000003378] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Bariatric surgery (BS) may be associated with significant malabsorption and nutritional deficiencies. METHODS Between March 1987 and January 2017, we performed 922 liver transplants (LT) at our institution; 33 had antecedent BS. We matched the BS cohort to LT recipients without BS (1:3 matching) based on exact matching for gender and cancer and inverse variance matching for age, LT body mass index, MELD score, and transplant date. RESULTS We analyzed outcomes in 132 LT recipients (33 BS; 99 non-BS). The BS cohort comprised 26 (79%) women with a mean age of 52.4 years. The BS procedures included 20 Roux-en-Y gastric bypass (61%), 6 jejunoileal bypass (18%), 3 gastric band (9%), 2 sleeve gastrectomy (6%), and 1 duodenal switch (3%). The primary indications for LT listing were alcoholic cirrhosis (9; 27%), nonalcoholic steatohepatitis (7; 21%), hepatitis C (8; 24%), and hepatocellular carcinoma (3; 9%). At LT, body mass index for the BS cohort was 29.6, and MELD was 24. Compared with matched controls, BS recipients did not have longer LT length of hospital stay (17.8 versus 15.7 d, P = 0.71), longer intensive care unit length of stay (5.3 versus 4.1 d, P = 0.16), or higher 30-day complication rate (76% versus 85%, P = 0.43). Overall patient survival was similar (1- and 3-y survival was 90.1% and 75.9% for BS; 90.9% and 76.4% for non-BS, P = 0.34). CONCLUSIONS A history of BS does not portend a deleterious effect on LT outcomes.
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Benhammou JN, Moon AM, Pisegna JR, Su F, Vutien P, Moylan CA, Ioannou GN. Nonalcoholic Fatty Liver Disease Risk Factors Affect Liver-Related Outcomes After Direct-Acting Antiviral Treatment for Hepatitis C. Dig Dis Sci 2021; 66:2394-2406. [PMID: 32654086 PMCID: PMC7854862 DOI: 10.1007/s10620-020-06457-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 06/28/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION In hepatitis C (HCV) patients, obesity and/or diabetes may increase the risk of liver-related outcomes. We aimed to determine whether diabetes and/or obesity are associated with adverse outcomes in direct-acting antiviral (DAA)-treated HCV patients. METHODS We conducted a retrospective study of 33,003 HCV-infected, DAA-treated Veterans between 2013 and 2015. Body mass index was used to categorize patients into underweight (< 18.5 kg/m2), normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2), obesity I (30 to < 35 kg/m2), and obesity II-III (> 35 kg/m2). Diabetes was defined by ICD-9/10 codes in association with hemoglobin A1c > 6.5% or medication prescriptions. Patients were followed from 180 days post-DAA initiation until 2/14/2019 to assess for development of cirrhosis, decompensations, hepatocellular carcinoma (HCC), and death. Multivariable Cox proportional hazards regression models were used to determine the association between diabetes and/or obesity and outcomes. RESULTS During a mean follow-up of 3 years, 10.1% patients died, 5.0% were newly diagnosed with cirrhosis, 4.7% had a decompensation and 4.0% developed HCC. Diabetes was associated with an increased risk of mortality (AHR = 1.25, 95% CI 1.10-1.42), cirrhosis (AHR = 1.31, 95% CI 1.16-1.48), decompensation (AHR = 1.74, 95% CI 1.31-2.31), and HCC (AHR = 1.32, 95% CI 1.01-1.72) among patients without baseline cirrhosis. Compared to normal-weight persons, obese persons had a higher risk of cirrhosis, but overweight and obese persons had lower risk of mortality and HCC. CONCLUSIONS In this large DAA-treated Veterans cohort, pre-DAA diabetes increases mortality and liver-related events independent of SVR. Continued vigilance is warranted in patients with diabetes despite SVR. Elevated BMI categories appear to have improved outcomes, although further studies are needed to understand those associations.
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Affiliation(s)
- Jihane N Benhammou
- Pfleger Liver Institute, University of California Los Angeles, 200 Medical Plaza, Los Angeles, CA, 90095, USA.
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA.
| | - Andrew M Moon
- Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, 130 Mason Farm Road, Bioinformatics Building CB#7080, Chapel Hill, NC, 27599-7080, USA
| | - Joseph R Pisegna
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA
| | - Feng Su
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Cynthia A Moylan
- Division of Gastroenterology, Veterans Affairs Health System, Durham, NC, USA
- Division of Gastroenterology, Duke University Health System, 905 Lasalle St., Gsrb 1 DUMC 3256, Durham, NC, 27710, USA
| | - George N Ioannou
- Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, 130 Mason Farm Road, Bioinformatics Building CB#7080, Chapel Hill, NC, 27599-7080, USA
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, S-111-Gastro, 1660 S. Columbian Way, Seattle, WA, 98108, USA
- Division of Gastroenterology, Veterans Affairs Puget Sound Health Care System, S-111-Gastro, 1660 S. Columbian Way, Seattle, WA, 98108, USA
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Ayonrinde OT. Historical narrative from fatty liver in the nineteenth century to contemporary NAFLD - Reconciling the present with the past. JHEP Rep 2021; 3:100261. [PMID: 34036255 PMCID: PMC8135048 DOI: 10.1016/j.jhepr.2021.100261] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 02/18/2021] [Accepted: 02/23/2021] [Indexed: 12/19/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide. This historical narrative traces the evolution from basic descriptions of fatty liver in the nineteenth century to our contemporary understanding of NAFLD in the twentieth and twenty-first centuries. A detailed historiographic review of fatty liver from 1800s onwards was performed alongside a brief review of contemporary associations. Archived published literature dating back to the 1800s describe clinicopathological features of fatty liver. In the nineteenth century, doyens of medicine associated fatty liver with alcohol, malnutrition or wasting conditions, and subsequently adiposity, unhealthy diets and sedentary lifestyle. Microscopically, fatty liver was described when 5% or more hepatocytes were distended with fat. Recommendations to reverse fatty liver included reducing consumption of fat, sugar, starchy carbohydrates and alcohol, plus increasing physical exercise. Fatty liver was associated with liver fibrosis and cirrhosis in the late 1800s, and with diabetes in the early 1900s. The diagnostic labels NAFLD and non-alcoholic steatohepatitis (NASH) were introduced in the late 1900s. Metabolic dysfunction-associated fatty liver disease (MAFLD) was recently proposed to update the nosology of fatty liver, recognising the similar metabolic pathogenesis evident in individuals with typical NAFLD and those with heterogenous "secondary" co-factors including alcohol and other aetiologies. Fatty liver has emerged from being considered a disorder of nutritional extremes or alcohol excess to contemporary recognition as a complex metabolic disorder that risks progression to cirrhosis and hepatocellular carcinoma. The increasing prevalence of NAFLD and our growing understanding of its lifestyle and metabolic determinants justify the current exercise of re-examining the evolution of this common metabolic disorder.
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Affiliation(s)
- Oyekoya T. Ayonrinde
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA, Australia
- Medical School, The University of Western Australia, Perth, WA, Australia
- Faculty of Health Sciences, Curtin University, Bentley, WA, Australia
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Taharboucht S, Guermaz R, Brouri M, Chibane A. Subclinical atherosclerosis and arterial stiffness in nonalcoholic fatty liver disease: A case-control study in Algerian population. JOURNAL DE MEDECINE VASCULAIRE 2021; 46:129-138. [PMID: 33990287 DOI: 10.1016/j.jdmv.2021.03.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 03/20/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) was described for the first time in 1980, and became within a few years one of the most frequent causes of chronic liver disease. However, during the last decade, many studies suggested a strong relationship between NAFLD and cardiovascular diseases including carotid atherosclerosis evoking the hypothesis that NAFLD is a factor or a marker of cardiovascular risk. In Algeria, data on this subject are rare or inexistent. The objective of our work was to study the relationship between NAFLD and atherosclerosis in an Algerian population without diabetes. PATIENTS AND METHODS It is a case-control study with a strict matching by age and sex. Non-diabetic participants between 30 and 70 years of age were consecutively included in the department of internal medicine of the public hospital of El Biar. The diagnosis of NAFLD was made by ultrasound and hepatic elasticity was assessed by FibroScan®. We collected the data of the carotid ultrasound, the carotid-femoral pulse wave velocity (cfPWV), ankle-brachial pressure index and arterial pressure (consultation and ambulatory monitoring). Non parametric statistical methods (chi 2 McNemar for the percentages, t Friedman test for medium) were used and the association between variables was estimated by odds ratio (OR). These analyses were performed using SPSS 21.0 software (IBM). RESULTS 213 patients with NAFLD, with a mean age of 48.5 years±10.14 (100 men/113 women) were matched to 213 controls. The presence of carotid atherosclerotic plaque (CAP) was higher in NAFLD than in controls (31.92% (n=68) vs. 7.05% (n=15), P<0.001). In multivariate analysis, the CAP (OR 8.6, 95% CI [3.6-20.5], P<0.001), high Intima media thickness (OR 2.8, 95% CI [1.4-5.4], P=0.002), CRP≥6mg/l (OR 14.7, 95% CI [5.9-36.9], P=0.001), abdominal obesity (OR 3.8, 95% CI [1.4-9.7], P=0.05), high cfPWV (OR 4.4, 95% CI [2.4-8.1], P<0.001), elevated alanine aminotransferase(OR 4.0, 95% CI [1.6-9.8], P=0.002), overall obesity (OR 2.0, 95% CI [1.0-3.8], P=0.03), dyslipidemia (OR 2.0, 95% CI [1.0-3.8], P=0.02), and elevated GGT (OR 2.8, 95% [1.1-7.1] were independently associated to NAFLD. CONCLUSION Our study suggests that NAFLD is significantly associated with carotid atherosclerosis and arterial stiffness. These results may have implications in the management of patients with NAFLD in terms of cardiovascular prevention.
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Affiliation(s)
- S Taharboucht
- Internal medecine department, CHU de Douera, University of Blida 1, Algiers, Algeria.
| | - R Guermaz
- Internal medecine department, EPH EL BIAR, University of Algiers, Algiers, Algeria
| | - M Brouri
- Internal medecine department, EPH EL BIAR, University of Algiers, Algiers, Algeria
| | - A Chibane
- Internal medecine department, CHU de Douera, University of Blida 1, Algiers, Algeria
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Song D, Li C, Wang Z, Zhao Y, Shen B, Zhao W. Association of non-alcoholic fatty liver disease with diabetic retinopathy in type 2 diabetic patients: A meta-analysis of observational studies. J Diabetes Investig 2021; 12:1471-1479. [PMID: 33372390 PMCID: PMC8354494 DOI: 10.1111/jdi.13489] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 10/06/2020] [Accepted: 12/24/2020] [Indexed: 12/25/2022] Open
Abstract
Aims/Introduction Non‐alcoholic fatty liver disease (NAFLD) is becoming more and more prevalent in type 2 diabetes mellitus. Evidence connecting NAFLD to diabetic retinopathy (DR) is increasing, but the results vary. Thus, we undertook a meta‐analysis to explore the effect of NAFLD on diabetic retinopathy in patients with type 2 diabetes mellitus. Materials and Methods PubMed, Embase, Cochrane and Scopus database were searched for until September 30, 2019. Original studies analyzing the association between NAFLD and diabetic retinopathy in the type 2 diabetic population were included. This meta‐analysis was processed by RevMan 5.3 software. Subgroup analyses based on countries were carried out. The pooled odds ratios and 95% confidence intervals were used to evaluate the association between NAFLD and diabetic retinopathy incidence. The I2 test was used to assess heterogeneity of studies. Results We retrieved 414 articles, and nine studies involving 7,170 patients were included in the final analysis. The pooled effects estimate suggested that NAFLD was not associated with the risk of diabetic retinopathy in patients with type 2 diabetes mellitus. Subgroup analysis suggested that in China, Korea and Iran, patients with type 2 diabetes mellitus with NAFLD had a decreased risk for diabetic retinopathy compared with the non‐NAFLD individuals. However, in Italy and India, patients with type 2 diabetes mellitus with NAFLD had an increased risk for diabetic retinopathy compared with the non‐NAFLD individuals. In addition, no relevance between NAFLD and diabetic retinopathy was found in America. Conclusions On the whole, there was no association between NAFLD and diabetic retinopathy in individuals with type 2 diabetes mellitus. However, subgroup analysis showed that a difference of country may have an influence on the result.
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Affiliation(s)
- Dandan Song
- Department of Endocrine and Metabolic Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chengqian Li
- Department of Endocrine and Metabolic Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhongchao Wang
- Department of Endocrine and Metabolic Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yuhang Zhao
- Department of Endocrine and Metabolic Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Baoming Shen
- Department of Information Management, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wenjuan Zhao
- Department of Endocrine and Metabolic Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
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Chakravarthy MV, Siddiqui MS, Forsgren MF, Sanyal AJ. Harnessing Muscle-Liver Crosstalk to Treat Nonalcoholic Steatohepatitis. Front Endocrinol (Lausanne) 2020; 11:592373. [PMID: 33424768 PMCID: PMC7786290 DOI: 10.3389/fendo.2020.592373] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 11/16/2020] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has reached epidemic proportions, affecting an estimated one-quarter of the world's adult population. Multiple organ systems have been implicated in the pathophysiology of NAFLD; however, the role of skeletal muscle has until recently been largely overlooked. A growing body of evidence places skeletal muscle-via its impact on insulin resistance and systemic inflammation-and the muscle-liver axis at the center of the NAFLD pathogenic cascade. Population-based studies suggest that sarcopenia is an effect-modifier across the NAFLD spectrum in that it is tightly linked to an increased risk of non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH), and advanced liver fibrosis, all independent of obesity and insulin resistance. Longitudinal studies suggest that increases in skeletal muscle mass over time may both reduce the incidence of NAFLD and improve preexisting NAFLD. Adverse muscle composition, comprising both low muscle volume and high muscle fat infiltration (myosteatosis), is highly prevalent in patients with NAFLD. The risk of functional disability conferred by low muscle volume in NAFLD is further exacerbated by the presence of myosteatosis, which is twice as common in NAFLD as in other chronic liver diseases. Crosstalk between muscle and liver is influenced by several factors, including obesity, physical inactivity, ectopic fat deposition, oxidative stress, and proinflammatory mediators. In this perspective review, we discuss key pathophysiological processes driving sarcopenia in NAFLD: anabolic resistance, insulin resistance, metabolic inflexibility and systemic inflammation. Interventions that modify muscle quantity (mass), muscle quality (fat), and physical function by simultaneously engaging multiple targets and pathways implicated in muscle-liver crosstalk may be required to address the multifactorial pathogenesis of NAFLD/NASH and provide effective and durable therapies.
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Affiliation(s)
| | - Mohammad S. Siddiqui
- Department of Internal Medicine and Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, United States
| | - Mikael F. Forsgren
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- AMRA Medical AB, Linköping, Sweden
| | - Arun J. Sanyal
- Department of Internal Medicine and Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, United States
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Lonardo A, Leoni S, Alswat KA, Fouad Y. History of Nonalcoholic Fatty Liver Disease. Int J Mol Sci 2020; 21:5888. [PMID: 32824337 PMCID: PMC7460697 DOI: 10.3390/ijms21165888] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 08/10/2020] [Accepted: 08/12/2020] [Indexed: 12/15/2022] Open
Abstract
Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig's seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of "NAFLD as a manifestation of the Metabolic Syndrome", to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.
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Affiliation(s)
- Amedeo Lonardo
- Ospedale Civile di Baggiovara, UOC Medicina Metabolica, Dipartimento di Medicina Interna Generale, d’Urgenza e post Acuzie, Azienda Ospedaliero-Universitaria di Modena, Via Giardini 1135, 41125 Modena, Italy
| | - Simona Leoni
- Internal Medicine Unit, Department of Digestive Diseases, S.Orsola-Malpighi Hospital, Via Massarenti 9, 40136 Bologna, Italy;
| | - Khalid A. Alswat
- Liver Research Center, Department of Medicine, College of Medicine, King Saud University, Riyadh 11322, Saudi Arabia;
| | - Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minya 19111, Egypt;
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Dapagliflozin not only improves hepatic injury and pancreatic endoplasmic reticulum stress, but also induces hepatic gluconeogenic enzymes expression in obese rats. Clin Sci (Lond) 2020; 133:2415-2430. [PMID: 31769484 DOI: 10.1042/cs20190863] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 11/12/2019] [Accepted: 11/26/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND With an increasing prevalence of obesity and metabolic syndrome, exploring the effects and delineating the mechanisms of possible therapeutic agents are of critical importance. We examined the effects of SGLT2 inhibitor-dapagliflozin on insulin resistance, hepatic gluconeogenesis, hepatic injury and pancreatic ER stress in high-fat diet-induced obese rats. MATERIALS AND METHODS Male Wistar rats were fed with normal diet (ND) or high-fat diet for 16 weeks. Then high-fat rats were given vehicle (HF) or dapagliflozin (1 mg/kg/day; HFDapa) or metformin (30 mg/kg/day; HFMet) for another 4 weeks. RESULTS We found that dapagliflozin ameliorated high-fat diet-induced insulin resistance. The fasting plasma glucose level was comparable among groups, although dapagliflozin treatment led to substantial glycosuria. Hepatic gluconeogenic enzymes, PEPCK, G6Pase and FBPase, expression was not different in HF rats compared with ND rats. Meanwhile, dapagliflozin-treated group exhibited the elevation of these enzymes in parallel with the rise of transcription factor CREB, co-factor PGC1α and upstream regulator SIRT1. Hepatic oxidative stress, inflammation and NAFLD activity score as well as hepatic and pancreatic ER stress and apoptosis in obese rats were attenuated by dapagliflozin. CONCLUSION We conclude that dapagliflozin improved obesity-related insulin resistance, hepatic and pancreatic injury independent of fasting plasma glucose level. Of note, dapagliflozin-induced glycosuria apparently triggered the up-regulation of hepatic gluconeogenic enzymes to prevent hypoglycemia.
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Torun D, Oguzkurt L, Sezer S, Zumrutdal A, Singan M, Adam FU, Ozdemir FN, Haberal M. Hepatic Subcapsular Steatosis as a Complication Associated with Intraperitoneal Insulin Treatment in Diabetic Peritoneal Dialysis Patients. Perit Dial Int 2020. [DOI: 10.1177/089686080502500617] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objectives The aim of this study was to evaluate hepatic subcapsular steatosis (HSS) and its association with clinical parameters in nondiabetic continuous ambulatory peritoneal dialysis (CAPD) patients and in diabetic CAPD patients receiving intraperitoneal (IP) or subcutaneous (SC) insulin. Design Cross-sectional study. Setting A tertiary-care university hospital. Patients 28 CAPD patients (17 males and 11 females; mean age 53.5 ± 14 years; mean CAPD duration 22.8 ± 9 months) were included in the study. 14 patients had type II diabetes mellitus and 14 were nondiabetics. In the diabetic group, 8 patients were receiving IP insulin and 6 were receiving SC insulin. Outcome Measures HSS was diagnosed on computed tomography without contrast administration. Other data collected were body mass index (BMI), weekly Kt/V, peritoneal equilibration test (PET) results, daily insulin dosage, duration of diabetes mellitus, duration of insulin treatment, dialysate glucose load, and serum findings for alanine aminotransferase, aspartate aminotransferase, albumin, and lipid profiles. Results HSS was detected in 5 of the 8 diabetics who were receiving IP insulin. None of the diabetics receiving SC insulin and none of the nondiabetic patients exhibited HSS. Daily insulin dosage [108 (95 – 108.5) vs 54 (36 – 72) U/day, p = 0.02], BMI [31 (30.5 – 36) vs 26.6 (26 – 30) kg/m2, p = 0.02], serum triglyceride level [194 (184 – 505) vs 69 (61 – 82) mg/dL, p = 0.04], and PET creatinine levels [D/P2 creat: 0.67 (0.54 – 0.74) vs 0.50 (0.50 – 0.56), p = 0.05; D/P4 creat: 0.75 (0.64 – 0.86) vs 0.60 (0.59 – 0.62), p = 0.02] were higher in diabetic patients receiving IP insulin who had HSS than in those who did not have HSS. PET glucose levels [D0/D2 glu: 0.40 (0.37 – 0.45) vs 0.50 (0.48 – 0.51), p = 0.03; D0/D4 glu: 0.36 (0.26 – 0.38) vs 0.44 (0.38 – 0.48), p = 0.04] were lower in diabetic patients receiving IP insulin who had HSS than in those who did not have HSS. Conclusions Our results suggest that IP insulin plays a more important role in the pathogenesis of HSS than glucose levels in diabetic CAPD patients. They also indicate that HSS is associated with higher daily insulin requirement, obesity, hypertriglyceridemia, and high peritoneal transport rate in diabetic CAPD patients receiving IP insulin.
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Affiliation(s)
- Dilek Torun
- Departments of Nephrology Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Adana
| | - Levent Oguzkurt
- Departments of Radiology, Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Adana
| | - Siren Sezer
- Departments of Nephrology, Baskent University Faculty of Medicine, Ankara, Turkey
| | - Aysegul Zumrutdal
- Departments of Nephrology Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Adana
| | - Metin Singan
- Departments of Nephrology Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Adana
| | - Fatma Ulku Adam
- Departments of Nephrology Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Adana
| | - Fatma Nurhan Ozdemir
- Departments of Nephrology, Baskent University Faculty of Medicine, Ankara, Turkey
| | - Mehmet Haberal
- General Surgery, Baskent University Faculty of Medicine, Ankara, Turkey
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Blood Metabolite Signatures of Metabolic Syndrome in Two Cross-Cultural Older Adult Cohorts. Int J Mol Sci 2020; 21:ijms21041324. [PMID: 32079087 PMCID: PMC7072935 DOI: 10.3390/ijms21041324] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 02/11/2020] [Accepted: 02/12/2020] [Indexed: 02/07/2023] Open
Abstract
Metabolic syndrome (MetS) affects an increasing number of older adults worldwide. Cross-cultural comparisons can provide insight into how factors, including genetic, environmental, and lifestyle, may influence MetS prevalence. Metabolomics, which measures the biochemical products of cell processes, can be used to enhance a mechanistic understanding of how biological factors influence metabolic outcomes. In this study we examined associations between serum metabolite concentrations, representing a range of biochemical pathways and metabolic syndrome in two older adult cohorts: The Tsuruoka Metabolomics Cohort Study (TMCS) from Japan (n = 104) and the Baltimore Longitudinal Study of Aging (BLSA) from the United States (n = 146). We used logistic regression to model associations between MetS and metabolite concentrations. We found that metabolites from the phosphatidylcholines-acyl-alkyl, sphingomyelin, and hexose classes were significantly associated with MetS and risk factor outcomes in both cohorts. In BLSA, metabolites across all classes were uniquely associated with all outcomes. In TMCS, metabolites from the amino acid, biogenic amines, and free fatty acid classes were uniquely associated with MetS, and metabolites from the sphingomyelin class were uniquely associated with elevated triglycerides. The metabolites and metabolite classes we identified may be relevant for future studies exploring disease mechanisms and identifying novel precision therapy targets for individualized medicine.
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Ballestri S, Mantovani A, Nascimbeni F, Lugari S, Lonardo A. Extra-hepatic manifestations and complications of nonalcoholic fatty liver disease. Future Med Chem 2019; 11:2171-2192. [PMID: 31538528 DOI: 10.4155/fmc-2019-0003] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 05/07/2019] [Indexed: 12/14/2022] Open
Abstract
This review article aims to synthesize the evidence regarding nonalcoholic fatty liver disease (NAFLD) as a systemic disorder. We critically discuss the metabolic syndrome and its components; the cardiovascular and the endocrine system; chronic respiratory disorders; the musculoskeletal system; the skin; and extra-hepatic tumors. We conclude that, while some of these extra-hepatic conditions clearly predispose to the development of secondary forms of NAFLD (typically hypothyroidism-induced NAFLD), others result from pre-existent NAFLD (e.g., certain extra-hepatic tumors) and others (such as Type 2 Diabetes) have, with NAFLD, mutual and bidirectional associations. Analyzed data imply that NAFLD is not merely a hepatic disease. It is also and possibly more importantly, a systemic disorder requiring a special awareness, a multidisciplinary approach and a multidimensional vision.
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Affiliation(s)
- Stefano Ballestri
- Azienda USL di Modena - Ospedale di Pavullo - UOC di Medicina - Pavullo (Mo), Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes & Metabolism, Department of Medicine, University & Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Fabio Nascimbeni
- AOU di Modena - Ospedale Civile di Baggiovara, UOC di Medicina ad indirizzo Metabolico-Nutrizionistico - Modena, Italy
| | | | - Amedeo Lonardo
- AOU di Modena - Ospedale Civile di Baggiovara, UOC di Medicina ad indirizzo Metabolico-Nutrizionistico - Modena, Italy
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Schedlbauer C, Blaue D, Gericke M, Blüher M, Starzonek J, Gittel C, Brehm W, Vervuert I. Impact of body weight gain on hepatic metabolism and hepatic inflammatory cytokines in comparison of Shetland pony geldings and Warmblood horse geldings. PeerJ 2019; 7:e7069. [PMID: 31211018 PMCID: PMC6557249 DOI: 10.7717/peerj.7069] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 05/06/2019] [Indexed: 01/02/2023] Open
Abstract
Background Non-alcoholic fatty liver disease is known as determining part of human obesity. The impact of body weight (BW) gain on liver metabolism has not been extensively investigated yet. Objectives To investigate hepatic alterations caused by increasing BW in ponies and horses. Animals A total of 19 non-obese equines (10 Shetland ponies, geldings; nine Warmblood horses, geldings). Methods Animals received 200% of their metabolizable maintenance energy requirements for 2 years. Serum alkaline phosphatase, glutamate dehydrogenase (GLDH), aspartate aminotransferase (AST), and gamma-glutamyl transferase activities and bile acids were analyzed several times during 2 years of hypercaloric diet. Hepatic lipid content and hepatic levels of the interleukin (IL)-6, tumor necrosis factor α (TNFα), cluster of differentiation (CD) 68, IL-1β, lipoprotein lipase (LPL), fatty acid-binding protein 1, chemerin and nuclear factor-κB mRNAs were assessed at the start of the study and after 1 and 2 years of excess energy intake. Results The mean (±SD) BW gain recorded during 2 years of excess energy intake was 29.9 ± 19.4% for ponies and 17 ± 6.74% for horses. The hepatic lipid content was not profoundly affected by increasing BW. Levels of the IL-6, TNFα, CD68 and IL-1β mRNAs did not change during BW gain. Levels of the chemerin mRNA increased significantly in both breeds (ponies: P = 0.02; horses: P = 0.02) in response to BW gain. Significant differences in serum GLDH and AST activities, serum bile acid concentrations and hepatic levels of the LPL mRNA were observed between ponies and horses at the end of the study. Conclusions Chemerin might represent an interesting marker for future equine obesity research. Interestingly, steatosis caused by increasing BW may occur later in the development of obesity in equines than in humans. Additionally, the hepatic metabolism exhibits differences between ponies and horses, which may explain in part the greater susceptibility of ponies to obesity-associated metabolic dysregulations.
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Affiliation(s)
- Carola Schedlbauer
- Leipzig University, Institute of Animal Nutrition, Nutrition Diseases and Dietetics, Leipzig, Saxony, Germany
| | - Dominique Blaue
- Leipzig University, Institute of Animal Nutrition, Nutrition Diseases and Dietetics, Leipzig, Saxony, Germany
| | - Martin Gericke
- Leipzig University, Institute of Anatomy, Leipzig, Saxony, Germany
| | - Matthias Blüher
- Leipzig University, Department of Medicine, Leipzig, Saxony, Germany
| | - Janine Starzonek
- Leipzig University, Institute of Animal Nutrition, Nutrition Diseases and Dietetics, Leipzig, Saxony, Germany
| | - Claudia Gittel
- Leipzig University, Department for Horses, Leipzig, Saxony, Germany
| | - Walter Brehm
- Leipzig University, Department for Horses, Leipzig, Saxony, Germany
| | - Ingrid Vervuert
- Leipzig University, Institute of Animal Nutrition, Nutrition Diseases and Dietetics, Leipzig, Saxony, Germany
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38
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Adams LC, Lübbe F, Bressem K, Wagner M, Hamm B, Makowski MR. Non-alcoholic fatty liver disease in underweight patients with inflammatory bowel disease: A case-control study. PLoS One 2018; 13:e0206450. [PMID: 30427909 PMCID: PMC6241122 DOI: 10.1371/journal.pone.0206450] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 10/13/2018] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) was shown to also occur in lean and underweight patients. So far, the prevalence of NAFLD in underweight individuals with and without inflammatory bowel disease (IBD) is insufficiently enlightened. In this cross-sectional age, gender and disease-matched case-control study, underweight patients (BMI<18.5 kg/m2) with inflammatory bowel disease (IBD), who underwent abdominal MRI at 1.5 T/3 T with fat-saturated fast-spin-echo imaging from 10/2005-07/2018 were analysed (control-to-case-ratio 1:1, n = 130). All patients were additionally investigated for duration, history of surgery, medical treatment, laboratory values, liver and spleen diameters. On MRI, liver fat was quantified by two observers based on the relative signal loss on T2-weighted fast spin-echo MR images with fat saturation compared to images without fat saturation. The prevalence of NAFLD/liver steatosis, defined as a measured intrahepatic fat content of at least 5%, was significantly higher in underweight IBD patients than in normal weight patients (87.6% versus 21.5%, p<0.001). Compared to the cases, the liver fat content of the controls was reduced by -0.19 units on average (-19%; 95%Cl: -0.20; -0.14). Similar results were obtained for the subgroup of non-IBD individuals (n = 12; -0.25 units on average (-25%); 95%Cl: -0.35; -0.14). Patients with extremely low body weight (BMI <17.5 kg/m2) showed the highest liver fat content (+0.15 units on average (+15%) compared to underweight patients with a BMI of 17.5-18.5 kg/m2 (p<0.05)). Furthermore, underweight patients showed slightly increased liver enzymes and liver diameters. There were no indications of significant differences in disease duration, type of medications or surgery between cases and controls and also, there were no significant differences between observers or field strengths (p>0.05). The prevalence of liver steatosis was higher among underweight IBD and non-IBD patients compared to normal weight controls. Also, underweight patients showed slightly increased liver enzymes and liver diameters, hinting at initial metabolic disturbances.
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Grants
- Deutsche Forschungsgemeinschaft
- BIH/Charité – Universitätsmedizin Berlin (DE)
- BH has received research grants for the Department of Radiology, Charité – Universitätsmedizin Berlin from the following companies: 1. Abbott, 2. Actelion Pharmaceuticals, 3. Bayer Schering Pharma, 4. Bayer Vital, 5. BRACCO Group, 6. Bristol-Myers Squibb, 7. Charite research organisation GmbH, 8. Deutsche Krebshilfe, 9. Dt. Stiftung für Herzforschung, 10. Essex Pharma, 11. EU Programmes, 12. Fibrex Medical Inc., 13. Focused Ultrasound Surgery Foundation, 14. Fraunhofer Gesellschaft, 15. Guerbet, 16. INC Research, 17. lnSightec Ud., 18. IPSEN Pharma, 19. Kendlel MorphoSys AG, 20. Lilly GmbH, 21. Lundbeck GmbH, 22. MeVis Medical Solutions AG, 23. Nexus Oncology, 24. Novartis, 25. Parexel Clinical Research Organisation Service, 26. Perceptive, 27. Pfizer GmbH, 28. Philipps, 29. Sanofis-Aventis S.A, 30. Siemens, 31. Spectranetics GmbH, 32. Terumo Medical Corporation, 33. TNS Healthcare GMbH, 34. Toshiba, 35. UCB Pharma, 36. Wyeth Pharma, 37. Zukunftsfond Berlin (TSB), 38. Amgen, 39. AO Foundation, 40. BARD, 41. BBraun, 42. Boehring Ingelheimer, 43. Brainsgate, 44. PPD (Clinical Research Organisation), 45. CELLACT Pharma, 46. Celgene, 47. CeloNova BioSciences, 48. Covance, 49. DC Deviees, Ine. USA, 50. Ganymed, 51. Gilead Sciences, 52. Glaxo Smith Kline, 53. ICON (Clinical Research Organisation), 54. Jansen, 55. LUX Bioseienees, 56. MedPass, 57. Merek, 58. Mologen, 59. Nuvisan, 60. Pluristem, 61. Quintiles, 62. Roehe, 63. Sehumaeher GmbH (Sponsoring eines Workshops), 64. Seattle Geneties, 65. Symphogen, 66. TauRx Therapeuties Ud., 67. Accovion, 68. AIO: Arbeitsgemeinschaft Internistische Onkologie, 69. ASR Advanced sleep research, 70. Astellas, 71. Theradex, 72. Galena Biopharma, 73. Chiltern, 74. PRAint, 75. lnspiremd, 76. Medronic, 77. Respicardia, 78. Silena Therapeutics, 79. Spectrum Pharmaceuticals, 80. St. Jude., 81. TEVA, 82. Theorem, 83. Abbvie, 84. Aesculap, 85. Biotronik, 86. Inventivhealth, 87. ISA Therapeutics, 88. LYSARC, 89. MSD, 90. novocure, 91. Ockham oncology, 92. Premier-research, 93. Psi-cro, 94. Tetec-ag, 94. Tetec-ag, 95. Winicker-norimed, 96. Achaogen Inc, 97. ADIR, 98. AstraZenaca AB, 99. Demira Inc, 100.Euroscreen S.A., 101. Galmed Research and Development Ltd., 102. GETNE, 103. Guidant Europe NV, 104. Holaira Inc., 105. Immunomedics Inc., 106. Innate Pharma, 107. Isis Pharmaceuticals Inc, 108. Kantar Health GmbH, 109. MedImmune Inc, 110. Medpace Germany GmbH (CRO), 111. Merrimack Pharmaceuticals Inc, 112. Millenium Pharmaceuticals Inc, 113. Orion Corporation Orion Pharma, 114. Pharmacyclics Inc, 115. PIQUR Therapeutics Ltd, 116. Pulmonx International Sárl, 117. Servier (CRO), 118. SGS Life Science Services (CRO), 119. Treshold Pharmaceuticals Inc.
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Affiliation(s)
- Lisa C. Adams
- Department of Radiology, Charité, Berlin, Germany
- * E-mail:
| | - Falk Lübbe
- Department of Radiology, Charité, Berlin, Germany
| | - Keno Bressem
- Department of Radiology, Charité, Berlin, Germany
| | | | - Bernd Hamm
- Department of Radiology, Charité, Berlin, Germany
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Kim K, Kim DS, Kim KN. Serum Alanine Aminotransferase Level as a Risk Factor for Coronary Heart Disease Prediction in Koreans: Analysis of the Korea National Health and Nutrition Examination Survey (V-1, 2010 and V-2, 2011). Korean J Fam Med 2018; 40:124-128. [PMID: 30419632 PMCID: PMC6444088 DOI: 10.4082/kjfm.17.0068] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 10/12/2017] [Indexed: 01/14/2023] Open
Abstract
Background The blood level of alanine aminotransferase (ALT) is associated with increased coronary heart disease (CHD) risk. However, its use as an independent factor for CHD risk prediction remains unclear in Asian populations. The purpose of this study was to examine the association between serum ALT levels and CHD risk in Koreans. Methods This was a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey (V-1, 2010 and V-2, 2011). The ALT levels of 3,215 individuals were analyzed. The Framingham Risk Score (FRS) modified by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) was used to compute the 10-year CHD risk prediction. Results Positive correlations were established between log-transformed ALT concentration and FRS (r=0.433, P<0.001). After adjusting for body mass index, low-density lipoprotein cholesterol, the amount of alcohol intake, and gamma-glutamyl transferase, the odds ratio (95% confidence interval) for intermediate or greater risk of 10-year CHD prediction (10-year risk ≥10%) for the lowest quartile of participants was 2.242 (1.405–3.577) for the second quartile, 2.879 (1.772–4.679) for the third quartile, and 3.041 (1.789–5.170) for the highest quartile. Conclusion In Koreans, a higher serum ALT concentration was significantly correlated with 10-year CHD risk prediction according to NCEP ATP III guidelines.
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Affiliation(s)
- Kiyoung Kim
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
| | - Dong Sun Kim
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
| | - Kyu-Nam Kim
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
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40
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Bae CR, Hino J, Hosoda H, Miyazato M, Kangawa K. C-type natriuretic peptide (CNP) in endothelial cells attenuates hepatic fibrosis and inflammation in non-alcoholic steatohepatitis. Life Sci 2018; 209:349-356. [PMID: 30114411 DOI: 10.1016/j.lfs.2018.08.031] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 08/09/2018] [Accepted: 08/12/2018] [Indexed: 12/13/2022]
Abstract
AIMS Our previous study revealed that mice transgenic for endothelial-cell-specific overexpression of CNP (E-CNP Tg mice) are protected against the increased fat weight, inflammation, and insulin resistance associated with high-fat diet (HFD)-induced obesity. In addition, E-CNP overexpression prevented abnormal lipid profiles and metabolism and blocked inflammation in the livers of HFD-fed mice. Because obesity, dyslipidemia, and insulin resistance increase the risk of various liver diseases, including non-alcoholic steatohepatitis (NASH), we here studied the role of E-CNP overexpression in the livers of mice in which NASH was induced through feeding of either HFD or a choline-deficient defined l‑amino-acid diet (CDAA). MAIN METHODS Wild-type (Wt) and E-CNP Tg mice were fed either a standard diet or HFD for 25 weeks or CDAA for 10 weeks. We then assessed hepatic and serum biochemistry; measured blood glucose during glucose tolerance test (GTT) and insulin tolerance test (ITT); evaluated hepatic fibrosis and inflammation; and performed hepatic histology and gene expression analysis. KEY FINDINGS Serum triglycerides, total cholesterol, non-esterified fatty acids, asparagine transaminase, glucose tolerance, and insulin resistance were ameliorated by CNP overexpression in endothelial cells of HFD-fed E-CNP Tg mice. In addition, hepatic fibrosis and inflammation were decreased in HFD-fed E-CNP Tg mice compared with HFD-fed Wt mice. CDAA-fed E-CNP Tg mice showed improved glycemic control, but liver parameters, fibrosis, and inflammation were remained elevated and equivalent to those in CDAA-fed Wt mice. SIGNIFICANCE The overexpression of CNP in endothelial cells has anti-fibrotic and anti-inflammatory effects in liver during HFD-induced NASH in mice.
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Affiliation(s)
- Cho-Rong Bae
- Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan
| | - Jun Hino
- Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
| | - Hiroshi Hosoda
- Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan
| | - Mikiya Miyazato
- Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan
| | - Kenji Kangawa
- Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan
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Schuster S, Cabrera D, Arrese M, Feldstein AE. Triggering and resolution of inflammation in NASH. Nat Rev Gastroenterol Hepatol 2018; 15:349-364. [PMID: 29740166 DOI: 10.1038/s41575-018-0009-6] [Citation(s) in RCA: 642] [Impact Index Per Article: 91.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) is considered the progressive form of nonalcoholic fatty liver disease (NAFLD) and is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. A central issue in this field relates to the identification of those factors that trigger inflammation, thus fuelling the transition from nonalcoholic fatty liver to NASH. These triggers of liver inflammation might have their origins outside the liver (such as in adipose tissue or the gut) as well as inside the organ (for instance, lipotoxicity, innate immune responses, cell death pathways, mitochondrial dysfunction and endoplasmic reticulum stress), both of which contribute to NASH development. In this Review, we summarize the currently available information on the key upstream triggers of inflammation in NASH. We further delineate the mechanisms by which liver inflammation is resolved and the implications of a defective pro-resolution process. A better knowledge of these mechanisms should help to design targeted therapies able to halt or reverse disease progression.
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Affiliation(s)
- Susanne Schuster
- Department of Pediatrics, University of California, San Diego, CA, USA
| | - Daniel Cabrera
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.,Departamento de Ciencias Químicas y Biológicas, Facultad de Salud, Universidad Bernardo O Higgins, Santiago, Chile
| | - Marco Arrese
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.,Centre for Aging and Regeneration (CARE), Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Ariel E Feldstein
- Department of Pediatrics, University of California, San Diego, CA, USA.
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Preuss HG, Kaats GR, Mrvichin N, Swaroop A, Bagchi D, Clouatre D, Preuss JM. Examining the Relationship Between Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome in Nondiabetic Subjects. J Am Coll Nutr 2018; 37:457-465. [PMID: 29652564 DOI: 10.1080/07315724.2018.1443292] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is considered by some to be the hepatic manifestation of the metabolic syndrome (MS). However, others believe NAFLD is a distinct entity that actually initiates MS. Whichever is true, a definite linkage exists between both is generally accepted based upon the frequency of common occurrence and realization that insulin resistance (IR) is and realization that. The objective is to better understand the relationship between NAFLD and MS. Specifically, is there any concrete evidence that development of NAFLD precedes MS or vice versa? Another goal was to better comprehend capabilities of circulating aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and their ratio used commonly for diagnosis of NAFLD. METHODS Data from 288 participants with fasting blood glucose (FBG) levels below the diabetic level (<125 mg/dL) and AST and ALT values in the normal range (<40 U/L) were examined. Correlations between ALT and AST and their ratio as independent variables with a variety of metabolic parameter were evaluated and compared. RESULTS Like FBG, many significant positive correlations among glucose-insulin indices, body composition, blood pressure, dyslipidemias, and inflammation were discovered using ALT, and less so with AST, as the independent variable. In some cases, even stronger correlations in a negative direction with IR and MS were found with the ratio AST/ALT. Corroboration occurred when values in the lowest and highest quartiles of ALT and AST/ALT readings showed appropriate statistically significant differences. CONCLUSIONS The findings here suggest that both NAFLD and the MS very early in development have a common inciting mechanism(s)-most likely IR. Accordingly, the early concurrent temporal results are consistent with the concept that NAFLD is a hepatic manifestation of the IR associated with the MS. They do not exclude the possibility that once some liver functional adjustments take place, several aspects of the MS are bolstered further, perhaps via intensified heightening of IR.
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Affiliation(s)
- Harry G Preuss
- a Department of Biochemistry , Georgetown University Medical Center , Washington, DC , USA
| | - Gilbert R Kaats
- b Integrative Health Technologies , San Antonio , Texas , USA
| | - Nate Mrvichin
- b Integrative Health Technologies , San Antonio , Texas , USA
| | - Anand Swaroop
- c Cepham Research Center , Piscataway , New Jersey , USA
| | - Debasis Bagchi
- c Cepham Research Center , Piscataway , New Jersey , USA.,d Department of Pharmacological and Pharmaceutical Services , University of Houston , Houston , Texas , USA
| | | | - Jeffrey M Preuss
- f Emergency Department , Veterans Administration Medical Center , Salem , Virginia , USA
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Martín-Guerrero SM, Muñoz-Gámez JA, Carrasco MC, Salmerón J, Martín-Estebané M, Cuadros MA, Navascués J, Martín-Oliva D. Poly(ADP-ribose)polymerases inhibitors prevent early mitochondrial fragmentation and hepatocyte cell death induced by H2O2. PLoS One 2017; 12:e0187130. [PMID: 29073231 PMCID: PMC5658148 DOI: 10.1371/journal.pone.0187130] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Accepted: 10/13/2017] [Indexed: 12/20/2022] Open
Abstract
Poly(ADP-ribose)polymerases (PARPs) are a family of NAD+ consuming enzymes that play a crucial role in many cellular processes, most clearly in maintaining genome integrity. Here, we present an extensive analysis of the alteration of mitochondrial morphology and the relationship to PARPs activity after oxidative stress using an in vitro model of human hepatic cells. The following outcomes were observed: reactive oxygen species (ROS) induced by oxidative treatment quickly stimulated PARPs activation, promoted changes in mitochondrial morphology associated with early mitochondrial fragmentation and energy dysfunction and finally triggered apoptotic cell death. Pharmacological treatment with specific PARP-1 (the major NAD+ consuming poly(ADP-ribose)polymerases) and PARP-1/PARP-2 inhibitors after the oxidant insult recovered normal mitochondrial morphology and, hence, increased the viability of human hepatic cells. As the PARP-1 and PARP-1/PARP-2 inhibitors achieved similar outcomes, we conclude that most of the PARPs effects were due to PARP-1 activation. NAD+ supplementation had similar effects to those of the PARPs inhibitors. Therefore, PARPs activation and the subsequent NAD+ depletion are crucial events in decreased cell survival (and increased apoptosis) in hepatic cells subjected to oxidative stress. These results suggest that the alterations in mitochondrial morphology and function seem to be related to NAD+ depletion, and show for the first time that PARPs inhibition abrogates mitochondrial fragmentation. In conclusion, the inhibition of PARPs may be a valuable therapeutic approach for treating liver diseases, by reducing the cell death associated with oxidative stress.
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Affiliation(s)
| | - José A. Muñoz-Gámez
- Instituto de Investigación Biomédica (ibsGranada), Hospital Universitario San Cecilio, Granada, Spain
| | - María-Carmen Carrasco
- Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain
| | - Javier Salmerón
- Instituto de Investigación Biomédica (ibsGranada), Hospital Universitario San Cecilio, Granada, Spain
| | - María Martín-Estebané
- Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain
| | - Miguel A. Cuadros
- Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain
| | - Julio Navascués
- Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain
| | - David Martín-Oliva
- Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain
- * E-mail:
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Liebig M, Hassanzada A, Kämmerling M, Genz B, Vollmar B, Abshagen K. Microcirculatory disturbances and cellular changes during progression of hepatic steatosis to liver tumors. Exp Biol Med (Maywood) 2017; 243:1-12. [PMID: 29065724 DOI: 10.1177/1535370217738730] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease is closely associated with metabolic syndrome and comprises a pathological spectrum of liver disease ranging from steatosis to steatohepatitis and can progress to fibrosis/cirrhosis and hepatocellular carcinoma. In 2013, a mouse model was described that mimics non-alcoholic fatty liver disease progression from steatohepatitis to tumors in a short time span and with high incidence. As microcirculatory disturbances play a crucial role in liver disease, the suitability of the steatosis-inflammation-tumor model for microcirculatory studies was assessed. Herein, we present a comprehensive view on morphological, microvascular, cellular, and functional aspects of non-alcoholic fatty liver disease progression in the steatosis-inflammation-tumor model using intravital microscopy, biochemical, and histological techniques. Mice develop steatohepatitis, mild fibrosis, and liver tumors at ages of 6, 12, and 20 weeks, respectively. Non-alcoholic fatty liver disease progression was accompanied by several general aspects of disease severity like increasing liver/body weight index, non-alcoholic fatty liver disease activity score, and hepatocellular apoptosis. Intravital microscopic analysis revealed significant changes in hepatic microcirculation with increasing structural alterations, elevated leukocyte adherence, and impaired nutritive perfusion. Non-alcoholic fatty liver disease was further characterized by a lower sinusoidal density with a striking rise at 20 weeks. The characteristic microcirculatory changes make the model a convenient tool for analysis of microcirculation during progression from steatosis to liver tumor. Impact statement Significant alterations of microcirculation contribute to progression of NAFLD, a chronic liver disease with increasing medical and socio-economic impact. Characterization of microcirculation in a NAFLD model reflecting all relevant stages of disease progression was still missing. Thus, we evaluated microcirculatory and cellular changes in a steatosis-inflammation-tumor model using in vivo microscopy. Analyses revealed increasing structural alterations, elevated leukocyte-endothelial interaction, and impaired nutritive perfusion. Thus, this model is suitable for further studies investigating therapeutic approaches targeting these progressive microcirculatory disturbances.
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Affiliation(s)
- Marie Liebig
- 1 Institute for Experimental Surgery, University Medicine Rostock, Rostock 18057, Germany
| | - Alireza Hassanzada
- 1 Institute for Experimental Surgery, University Medicine Rostock, Rostock 18057, Germany
| | - Malte Kämmerling
- 1 Institute for Experimental Surgery, University Medicine Rostock, Rostock 18057, Germany
| | - Berit Genz
- 1 Institute for Experimental Surgery, University Medicine Rostock, Rostock 18057, Germany.,2 QIMR Berghofer Medical Research Institute, Brisbane QLD 4006, Australia
| | - Brigitte Vollmar
- 1 Institute for Experimental Surgery, University Medicine Rostock, Rostock 18057, Germany
| | - Kerstin Abshagen
- 1 Institute for Experimental Surgery, University Medicine Rostock, Rostock 18057, Germany
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Lonardo A, Nascimbeni F, Maurantonio M, Marrazzo A, Rinaldi L, Adinolfi LE. Nonalcoholic fatty liver disease: Evolving paradigms. World J Gastroenterol 2017; 23:6571-6592. [PMID: 29085206 PMCID: PMC5643282 DOI: 10.3748/wjg.v23.i36.6571] [Citation(s) in RCA: 137] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 08/21/2017] [Accepted: 09/05/2017] [Indexed: 02/06/2023] Open
Abstract
In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including "lean NAFLD" has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.
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Affiliation(s)
- Amedeo Lonardo
- Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, 41126 Modena, Italy
| | - Fabio Nascimbeni
- Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, 41126 Modena, Italy
- University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Mauro Maurantonio
- Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, 41126 Modena, Italy
| | - Alessandra Marrazzo
- Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, 41126 Modena, Italy
- University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Luca Rinaldi
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy
| | - Luigi Elio Adinolfi
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy
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Thoefner LB, Rostved AA, Pommergaard HC, Rasmussen A. Risk factors for metabolic syndrome after liver transplantation: A systematic review and meta-analysis. Transplant Rev (Orlando) 2017; 32:69-77. [PMID: 28501338 DOI: 10.1016/j.trre.2017.03.004] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 02/10/2017] [Accepted: 03/10/2017] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Metabolic syndrome is associated with increased risk of cardiovascular events, which contributes to the elevated mortality rate among liver transplant recipients. The objective of this systematic review and meta-analysis was to assess the prevalence and risk factors for metabolic syndrome after liver transplantation. METHODS The databases Medline and Scopus were searched for observational studies evaluating prevalence and risk factors for metabolic syndrome after liver transplantation. Meta-analyses were performed based on odds ratios (ORs) from multivariable analyses. The Newcastle-Ottawa Scale was used for assessment of bias. RESULTS The literature search generated 1815 records of which 16 articles were included comprising 3539 patients. The post-transplant prevalence of metabolic syndrome was 39%. Eight studies were eligible for meta-analyses, which showed that pre-transplant diabetes (OR=3.54, 95% confidence interval (CI): 2.51-4.98) and pre-transplant obesity (OR=2.44, 95% CI: 1.48-4.03) were risk factors for metabolic syndrome. Six out of seven studies reported that recipients with metabolic syndrome had a higher incidence of cardiovascular events. Four studies showed that survival was not affected by metabolic syndrome. CONCLUSIONS The prevalences of metabolic syndrome and new-onset metabolic syndrome were high after liver transplantation. Metabolic syndrome was associated with cardiovascular events, but not poorer survival. Patients with pre-transplant diabetes and -obesity are at high risk of metabolic syndrome and should be under careful surveillance in order to prevent, earlier diagnose, and treat metabolic syndrome and thereby limit the risk of cardiovascular events.
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Affiliation(s)
- Line Buch Thoefner
- Rigshospitalet - University of Copenhagen, Department of Surgical Gastroenterology and Transplantation, Abdominal Centre, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| | - Andreas Arendtsen Rostved
- Rigshospitalet - University of Copenhagen, Department of Surgical Gastroenterology and Transplantation, Abdominal Centre, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Hans-Christian Pommergaard
- Rigshospitalet - University of Copenhagen, Department of Surgical Gastroenterology and Transplantation, Abdominal Centre, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Allan Rasmussen
- Rigshospitalet - University of Copenhagen, Department of Surgical Gastroenterology and Transplantation, Abdominal Centre, Blegdamsvej 9, 2100 Copenhagen, Denmark
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Yoon CY, Lee M, Kim SU, Lim H, Chang TI, Kee YK, Han SG, Han IM, Kwon YE, Park KS, Lee MJ, Park JT, Han SH, Ahn SH, Kang SW, Yoo TH. Fatty liver associated with metabolic derangement in patients with chronic kidney disease: A controlled attenuation parameter study. Kidney Res Clin Pract 2017; 36:48-57. [PMID: 28392997 PMCID: PMC5331975 DOI: 10.23876/j.krcp.2017.36.1.48] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2016] [Revised: 08/06/2016] [Accepted: 09/23/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Hepatic steatosis measured with controlled attenuation parameter (CAP) using transient elastography predicts metabolic syndrome in the general population. We investigated whether CAP predicted metabolic syndrome in chronic kidney disease patients. METHODS CAP was measured with transient elastography in 465 predialysis chronic kidney disease patients (mean age, 57.5 years). RESULTS The median CAP value was 239 (202-274) dB/m. In 195 (41.9%) patients with metabolic syndrome, diabetes mellitus was more prevalent (105 [53.8%] vs. 71 [26.3%], P < 0.001), with significantly increased urine albumin-to-creatinine ratio (184 [38-706] vs. 56 [16-408] mg/g Cr, P = 0.003), high sensitivity C-reactive protein levels (5.4 [1.4-28.2] vs. 1.7 [0.6-9.9] mg/L, P < 0.001), and CAP (248 [210-302] vs. 226 [196-259] dB/m, P < 0.001). In multiple linear regression analysis, CAP was independently related to body mass index (β = 0.742, P < 0.001), triglyceride levels (β = 2.034, P < 0.001), estimated glomerular filtration rate (β = 0.316, P = 0.001), serum albumin (β = 1.386, P < 0.001), alanine aminotransferase (β = 0.064, P = 0.029), and total bilirubin (β = -0.881, P = 0.009). In multiple logistic regression analysis, increased CAP was independently associated with increased metabolic syndrome risk (per 10 dB/m increase; odds ratio, 1.093; 95% confidence interval, 1.009-1.183; P = 0.029) even after adjusting for multiple confounding factors. CONCLUSION Increased CAP measured with transient elastography significantly correlated with and could predict increased metabolic syndrome risk in chronic kidney disease patients.
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Affiliation(s)
- Chang-Yun Yoon
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - Misol Lee
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - Seung Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Hyunsun Lim
- Department of Policy Research Affairs, National Health Insurance Service Ilsan Hospital, Goyang,
Korea
| | - Tae Ik Chang
- Department of Internal Medicine, NHIS Medical Center, Ilsan Hospital, Goyang,
Korea
| | - Youn Kyung Kee
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - Seung Gyu Han
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - In Mee Han
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - Young Eun Kwon
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - Kyoung Sook Park
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - Mi Jung Lee
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - Jung Tak Park
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - Seung Hyeok Han
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
- Brain Korea 21 Project for Medical Science, Seoul,
Korea
| | - Shin-Wook Kang
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
- Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul,
Korea
| | - Tae-Hyun Yoo
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul,
Korea
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Li H, Clarke JD, Dzierlenga AL, Bear J, Goedken MJ, Cherrington NJ. In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice. J Biochem Mol Toxicol 2017; 31:10.1002/jbt.21840. [PMID: 27712037 PMCID: PMC5426479 DOI: 10.1002/jbt.21840] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Revised: 08/30/2016] [Accepted: 09/01/2016] [Indexed: 12/17/2022]
Abstract
Nonalcoholic steatohepatitis (NASH) has been identified as a source of significant interindividual variation in drug metabolism. A previous ex vivo study demonstrated significant changes in hepatic Cytochrome P450 (CYP) activity in human NASH. This study evaluated the in vivo activities of multiple CYP isoforms simultaneously in prominent diabetic NASH mouse models. The pharmacokinetics of CYP selective substrates: caffeine, losartan, and omeprazole changed significantly in a diabetic NASH mouse model, indicating attenuation of the activity of Cyp1a2 and Cyp2c29, respectively. Decreased mRNA expression of Cyp1a2 and Cyp2c29, as well as an overall decrease in CYP protein expression, was found in the diabetic NASH mice. Overall, these data suggest that the diabetic NASH model only partially recapitulates the human ex vivo CYP alteration pattern. Therefore, in vivo determination of the effects of NASH on CYP activity should be conducted in human, and more appropriate models are required for future drug metabolism studies in NASH.
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Affiliation(s)
- Hui Li
- Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721, USA
| | - John D. Clarke
- Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721, USA
| | - Anika L. Dzierlenga
- Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721, USA
| | - John Bear
- Statistical Consulting Lab, Univeristy of Arizona, Tucson, AZ, 85721, USA
| | - Michael J. Goedken
- Translational Sciences, Research Pathology Services, Rutgers University, New Brunswick, NJ 08854, USA
| | - Nathan J. Cherrington
- Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721, USA
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Bellentani S, Bedogni G, Miglioli L, Tiribelli C. The epidemiology of non-alcoholic fatty liver disease. Liver Int 2017; 37 Suppl 1:81-84. [PMID: 28052624 DOI: 10.1111/liv.13299] [Citation(s) in RCA: 436] [Impact Index Per Article: 54.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Accepted: 10/31/2016] [Indexed: 12/11/2022]
Abstract
The increase in Non-alcoholic Fatty Liver Disease (NAFLD) and the imminent disappearance of chronic viral hepatitis thanks to new and effective therapies is motivating hepatologists to change their clinical approach to chronic liver disease. NAFLD-cirrhosis or NAFLD-Hepatocellular Carcinoma (HCC) are now the second cause of liver transplantation in the USA. This short-review is focused to the epidemiology of NAFLD/Non-alchoholic Steatohepatitis (NASH), including the definition of this disease which should be revised as well discussing the prevalence, risk factors for progression, natural history and mortality. NAFLD is considered to be the hepatic manifestation of the metabolic syndrome (MS). It affects 25-30% of the general population and the risk factors are almost identical to those of MS. The natural history involves either the development of cardiovascular diseases or cirrhosis and HCC. HCC can also develop in NASH in the absence of cirrhosis (45% of cases). We conclude that an international consensus conference on the definition, natural history, policies of surveillance and new pharmacological treatments of NAFLD and NASH is urgently needed.
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Affiliation(s)
- Stefano Bellentani
- Gastroenterology and Hepatology Service, Clinica Santa Chiara, Locarno, Switzerland
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50
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Lin TY, Chen YJ, Chen WL, Peng TC. The Relationship between Nonalcoholic Fatty Liver Disease and Retinopathy in NHANES III. PLoS One 2016; 11:e0165970. [PMID: 27802330 PMCID: PMC5089732 DOI: 10.1371/journal.pone.0165970] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 10/20/2016] [Indexed: 01/14/2023] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD), an emerging multisystem disease, has the similar pathogenesis with diabetes and is prevalent in diabetes. This study investigated whether NAFLD is associated with retinopathy in individuals with diabetes and without diabetes. Methods The association between NAFLD and retinopathy was investigated in 5963 participants aged 40 years and older who participated in the NHANES III, a nationally representative, population-based and cross-sectional study. NAFLD was detected via ultrasonography, and fundus photographs were obtained to grade retinopathy patterns. We performed multivariate logistic regression analysis to investigate the relationship between the presence of retinopathy and NAFLD and diabetes. Results After adjusting for multiple covariates, NAFLD population had no evidence of retinopathy increase in population without diabetes (odds ratio [OR]: 0.77; 95% confidence interval [CI]: 0.48 to 1.26). In addition, NAFLD in individuals with diabetes was not significantly associated with retinopathy (OR: 0.77; 95% CI: 0.47 to 1.26), independent of age, gender, ethnicity, waist circumference, serum high-density lipoprotein (HDL) cholesterol, serum triglycerides, systolic blood pressure, and glycated hemoglobin. Conclusions In the US general population, NAFLD is not a precipitating factor of retinopathy in population with or without diabetes.
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Affiliation(s)
- Tzu-Yu Lin
- Department of Ophthalmology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Ying-Jen Chen
- Department of Ophthalmology, Tri-Service General Hospital, and School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Liang Chen
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, and School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, and School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Tao-Chun Peng
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, and School of Medicine, National Defense Medical Center, Taipei, Taiwan
- * E-mail:
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