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1
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Shroff H, Gallagher H. Multidisciplinary Care of Alcohol-related Liver Disease and Alcohol Use Disorder: A Narrative Review for Hepatology and Addiction Clinicians. Clin Ther 2023; 45:1177-1188. [PMID: 37813775 DOI: 10.1016/j.clinthera.2023.09.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 09/14/2023] [Accepted: 09/19/2023] [Indexed: 10/11/2023]
Abstract
PURPOSE Models of integrated, multidisciplinary care are optimal in the setting of complex, chronic diseases and in the overlap of medical and mental health disease, both of which apply to alcohol-related liver disease (ALD). Alcohol use disorder (AUD) drives nearly all cases of ALD, and coexisting mental health disease is common. ALD is a complex condition with severe clinical manifestations and high mortality that can occasionally lead to liver transplantation. As a result, integrated care for ALD is an attractive proposition. The aim of this narrative review was to: (1) review the overlapping and concerning trends in the epidemiology of AUD and ALD; (2) use a theoretical framework for integrated care known as the "five-component model" as a basis to highlight the need for integrated care and the overlapping clinical manifestations and management of the 2 conditions; and (3) review the existing applications of integrated care in this area. METHODS We performed a narrative review of epidemiology, clinical manifestations, and management strategies in AUD and ALD, with a particular focus on areas of overlap that are pertinent to clinicians who manage each disease. Previously published models were reviewed for integrating care in AUD and ALD, both in the general ALD population and in the setting of liver transplantation. FINDINGS The incidences of AUD and ALD are rising, with a pronounced acceleration driven by the Coronavirus Disease 2019 pandemic. Hepatologists are underprepared to diagnose and treat AUD despite its high prevalence in patients with liver disease. A patient who presents with overlapping clinical manifestations of both AUD and ALD may not fit neatly into typical treatment paradigms for each individual disease but rather will require new management strategies that are appropriately adapted. As a result, the dimensions of integrated care, including collective ownership of shared goals, interdependence among providers, flexibility of roles, and newly created professional activities, are highly pertinent to the holistic management of both diseases. IMPLICATIONS Integrated care models have proliferated as recognition grows of the dual pathology of AUD and ALD. Ongoing coordination across disciplines and research in the fields of hepatology and addiction medicine are needed to further elucidate optimal mechanisms for collaboration and improved quality of care.
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Affiliation(s)
- Hersh Shroff
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
| | - Heather Gallagher
- Substance Treatment and Recovery Program, University of North Carolina Hospital, Chapel Hill, North Carolina, USA
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2
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Nemati A, Nikniaz Z, Mota A. Effects of Resveratrol Supplementation on Nonalcoholic Fatty Liver Disease Management. TOP CLIN NUTR 2023. [DOI: 10.1097/tin.0000000000000314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/30/2023]
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3
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Lamboglia CG, Mccurdy AP, Kim YB, Lindeman C, Mangan AJ, Sivak A, Mager D, Spence JC. Investigation of movement-related behaviors and energy compensation in people living with liver disease: A scoping review. J Sports Sci 2022; 40:1299-1307. [PMID: 35766978 DOI: 10.1080/02640414.2022.2065087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2022] [Indexed: 10/17/2022]
Abstract
The importance of integrated movement behaviours (MB, i.e., physical activity [PA], sedentary behaviour, and sleep) and their interdependence for health has been recently discussed in the literature. The proposition that the amount of time spent in any one of these behaviours may impact the amount of time spent in another is supported by the ActivityStat hypothesis. The aim of this review is to (1) to assess whether individuals with liver disease display MB and/or energy (i.e., total energy expenditure [EE], basal EE, resting EE, and activity EE) compensation throughout the day and/or days; and (2) to examine whether a prescribed PA intervention triggers compensatory responses. Documents were included if they focused on people living with liver disease; analysed MB and/or EE components; were data-based; and were published in English. Fifteen documents were included in the final synthesis. The one finding that addressed research question 1 showed no compensatory response. As for research question 2, most of the findings suggest no compensation effects in response to a PA intervention. There is insufficient evidence to support the ActivityStat hypothesis in people living with liver disease. Further research should be conducted to test this hypothesis using standardized methodological procedures.
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Affiliation(s)
| | - Ashley P Mccurdy
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Yeong-Bae Kim
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Cliff Lindeman
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Amie J Mangan
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Allison Sivak
- H.T. Coutts Library, University of Alberta, Edmonton, Alberta, Canada
| | - Diana Mager
- Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - John C Spence
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
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4
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Ballestri S, Tana C, Di Girolamo M, Fontana MC, Capitelli M, Lonardo A, Cioni G. Semi-Quantitative Ultrasonographic Evaluation of NAFLD. Curr Pharm Des 2021; 26:3915-3927. [PMID: 32303161 DOI: 10.2174/1381612826666200417142444] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 03/20/2020] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) embraces histopathological entities ranging from the relatively benign simple steatosis to the progressive form nonalcoholic steatohepatitis (NASH), which is associated with fibrosis and an increased risk of progression to cirrhosis and hepatocellular carcinoma. NAFLD is the most common liver disease and is associated with extrahepatic comorbidities including a major cardiovascular disease burden. The non-invasive diagnosis of NAFLD and the identification of subjects at risk of progressive liver disease and cardio-metabolic complications are key in implementing personalized treatment schedules and follow-up strategies. In this review, we highlight the potential role of ultrasound semiquantitative scores for detecting and assessing steatosis severity, progression of NAFLD, and cardio-metabolic risk. Ultrasonographic scores of fatty liver severity act as sensors of cardio-metabolic health and may assist in selecting patients to submit to second-line non-invasive imaging techniques and/or liver biopsy.
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Affiliation(s)
- Stefano Ballestri
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | - Claudio Tana
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | - Maria Di Girolamo
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | | | - Mariano Capitelli
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | - Amedeo Lonardo
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | - Giorgio Cioni
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
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5
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Baker CJ, Martinez-Huenchullan SF, D'Souza M, Xu Y, Li M, Bi Y, Johnson NA, Twigg SM. Effect of exercise on hepatic steatosis: Are benefits seen without dietary intervention? A systematic review and meta-analysis. J Diabetes 2021; 13:63-77. [PMID: 32667128 DOI: 10.1111/1753-0407.13086] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 06/21/2020] [Accepted: 07/07/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Interventions involving both exercise and dietary modification are effective in reducing steatosis in nonalcoholic fatty liver disease (NAFLD). However, exercise alone may reduce liver fat and is known to have other positive effects on health. The primary aim of this study was to systematically review the effect of exercise alone without dietary intervention on NAFLD and to examine correlations across changes in liver fat and metabolic markers during exercise. METHODS Relevant online databases were searched from earliest records to May 2020 by two researchers. Studies were included where the trial was a randomized controlled trial, participants were adults, exercise intervention was longer than 4 weeks, no dietary intervention occurred, and the effect of the intervention on liver fat was quantified via magnetic resonance imaging/proton magnetic resonance spectroscopy. RESULTS Of 21 597 studies retrieved, 16 were included involving 706 participants. Exercise was found to have a beneficial effect on liver fat without dietary modification (-2.4%, -3.13 to -1.66) (mean, 95% CI). Pearson correlation showed significant relationships between change in liver fat and change in weight (r = 0.67, P = .007), liver enzymes aspartate aminotransferase (r = 0.76, P = .002) and alanine aminotransferase (r = 0.91, P < .001), and cardiorespiratory fitness VO2 peak (peak volume oxygen consumption) (r = -0.88, P = .004). By multivariate regression, change in weight and change in VO2 peak significantly contributed to change in liver fat (R2 = 0.84, P = .01). CONCLUSIONS This systematic review found that exercise without dietary intervention improves liver fat and that clinical markers may be useful proxies for quantifying liver fat changes.
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Affiliation(s)
- Callum John Baker
- Greg Brown Diabetes & Endocrinology Laboratory, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Sergio Francisco Martinez-Huenchullan
- Greg Brown Diabetes & Endocrinology Laboratory, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- School of Physical Therapy, Faculty of Medicine, Austral University of Chile, Valdivia, Chile
| | - Mario D'Souza
- Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Yu Xu
- Shanghai Institute of Endocrine and Metabolic Disease, Shanghai Ruijin Hospital, Shanghai, China
| | - Mian Li
- Shanghai Institute of Endocrine and Metabolic Disease, Shanghai Ruijin Hospital, Shanghai, China
| | - Yufang Bi
- School of Physical Therapy, Faculty of Medicine, Austral University of Chile, Valdivia, Chile
| | - Nathan Anthony Johnson
- Faculty of Health Sciences, University of Sydney, Sydney, New South Wales, Australia
- Boden Collaboration of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia
| | - Stephen Morris Twigg
- Greg Brown Diabetes & Endocrinology Laboratory, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
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Shi T, Wu L, Ma W, Ju L, Bai M, Chen X, Liu S, Yang X, Shi J. Nonalcoholic Fatty Liver Disease: Pathogenesis and Treatment in Traditional Chinese Medicine and Western Medicine. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2020; 2020:8749564. [PMID: 31998400 PMCID: PMC6969649 DOI: 10.1155/2020/8749564] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 11/14/2019] [Accepted: 11/20/2019] [Indexed: 01/30/2023]
Abstract
Nonalcoholic Fatty Liver Disease (NAFLD) is one of the most important causes of liver disease worldwide and probably destined to become the leading cause of end-stage liver disease in the coming decades, affecting both adults and children. Faced with the severe challenges for the prevention and control of NAFLD, this article discusses the understanding and mechanism of NAFLD from Chinese and Western medicine. Moreover, the progress regarding its treatment in both Chinese and Western medicine is also summarized. Both Chinese medicine and Western medicine have their own characteristics and clinical efficacy advantages in treating diseases. The purpose of this article is to hope that Chinese and Western medicine have complementary advantages, complementing each other to improve clinical NAFLD therapy prevention and treatment methods to receive more and more attention throughout the global medical community.
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Affiliation(s)
- Tingting Shi
- The Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310023, Zhejiang, China
| | - Li Wu
- Center of Clinical Evaluation, The First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, Zhejiang, China
| | - Wenjun Ma
- The Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310023, Zhejiang, China
| | - Liping Ju
- The Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310023, Zhejiang, China
| | - Minghui Bai
- The Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310023, Zhejiang, China
| | - Xiaowei Chen
- The Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310023, Zhejiang, China
| | - Shourong Liu
- The Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310023, Zhejiang, China
| | - Xingxin Yang
- College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, 1076 Yuhua Road, Kunming 650500, Yunnan, China
| | - Junping Shi
- Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
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7
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Khneizer G, Rizvi S, Gawrieh S. Non-alcoholic Fatty Liver Disease and Diabetes Mellitus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1307:417-440. [PMID: 32424494 DOI: 10.1007/5584_2020_532] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading liver disease globally. NAFLD patients can have a progressive phenotype, non-alcoholic steatohepatitis (NASH) that could lead to cirrhosis, liver failure and cancer. There is a close bi-directional relationship between NAFLD and type 2 diabetes mellitus (T2DM); NAFLD increases the risk for T2DM and its complications whereas T2DM increases the severity of NAFLD and its complications. The large global impact of NAFLD and T2DM on healthcare systems requires a paradigm shift from specialty care to early identification and risk stratification of NAFLD in primary care and diabetes clinics. Approach to diagnosis, risk stratification and management of NAFLD is discussed. In addition to optimizing the control of coexisting cardiometabolic comorbidities, early referral of NAFLD patients at high risk of having NASH or significant fibrosis to hepatology specialist care may improve management and allow access for clinical trials. Lifestyle modifications, vitamin E, pioglitazone and metformin are currently available options that may benefit patients with T2DM and NAFLD. The burst of clinical trials investigating newer therapeutic agents for NAFLD and NASH offer hope for new, effective and safe therapies in the near future.
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Affiliation(s)
- Gebran Khneizer
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Syed Rizvi
- A&M College of Medicine, Round Rock, Austin, TX, USA
| | - Samer Gawrieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
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8
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Ballestri S, Nascimbeni F, Lugari S, Lonardo A, Francica G. A critical appraisal of the use of ultrasound in hepatic steatosis. Expert Rev Gastroenterol Hepatol 2019; 13:667-681. [PMID: 31104523 DOI: 10.1080/17474124.2019.1621164] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Introduction: Nonalcoholic fatty liver disease (NAFLD) spans steatosis through nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). NAFLD carries an increased risk of cardio-metabolic and liver-related events accounting for a substantial economic burden. Given that the natural history of NAFLD is critically dependent on the stage of fibrosis, non-invasively identifying the subgroup of patients at a higher risk of progressive disease is key. Areas covered: This review highlights the recent developments in the use of ultrasound-based techniques in NAFLD and their performance in predicting metabolic derangements, cardiovascular risk, and progression of liver disease, notably including diagnosis of fibrosing NASH, identification, and treatment of HCC. Expert opinion: Our ability to identify NAFLD patients and to estimate steatofibrosis with various ultrasound-based techniques has undergone tremendous progress over the last few years. However, it is more difficult to capture the inflammatory component of NASH with such ultrasound-assisted techniques. Moreover, semi-quantitative, quantitative, elastographic, and contrast-enhanced ultrasound techniques are increasingly being appreciated and made available but not all such techniques will gain success in the clinical and research area. Therefore, further research will precisely define the role of the most innovative ultrasonographic techniques, while reducing costs and increasing feasibility.
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Affiliation(s)
- Stefano Ballestri
- a Internal Medicine Unit , Azienda USL of Modena, Pavullo Hospital , Modena , Italy
| | - Fabio Nascimbeni
- b Ospedale Civile di Baggiovara, Metabolic Medicine Unit , Azienda Ospedaliero Universitaria of Modena , Modena , Italy
| | - Simonetta Lugari
- c Ospedale Civile di Baggiovara, Metabolic Medicine Unit , Azienda Ospedaliero-Universitaria of Modena and University of Modena and Reggio Emilia , Modena , Italy
| | - Amedeo Lonardo
- b Ospedale Civile di Baggiovara, Metabolic Medicine Unit , Azienda Ospedaliero Universitaria of Modena , Modena , Italy
| | - Giampiero Francica
- d Interventional Ultrasound Unit , Pineta Grande Hospital , Castel Volturno , Italy
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9
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Abstract
PURPOSE OF REVIEW Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in the United States and is strongly associated to the metabolic syndrome. In this review, we will discuss the evidence behind the current recommendations on lifestyle modifications and available treatment options for NAFLD. RECENT FINDINGS The unrelenting rise in obesity and diabetes epidemic has led to a large healthcare burden from NAFLD and it is projected to continue to grow over the next two decades. Lifestyle modification that leads to weight loss is effective at treating NAFLD, but these modifications require a multidisciplinary approach for success in the real world. Multiple pharmacologic treatment options have been studied with promising results, but none have been approved for treatment in the United States. Clinical trials are on-going to study further pharmacologic treatment alternatives. SUMMARY NAFLD is the most common chronic liver disease in United States, and an independent risk factor for mortality. Implementation of lifestyle modifications through a multidisciplinary approach and careful selection of patients for pharmacologic interventions will be essential for successful management of NAFLD.
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10
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Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol 2017; 67:829-846. [PMID: 28545937 DOI: 10.1016/j.jhep.2017.05.016] [Citation(s) in RCA: 880] [Impact Index Per Article: 110.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Revised: 05/09/2017] [Accepted: 05/15/2017] [Indexed: 02/06/2023]
Abstract
Lifestyle intervention can be effective when treating non-alcoholic fatty liver diseases (NAFLD) patients. Weight loss decreases cardiovascular and diabetes risk and can also regress liver disease. Weight reductions of ⩾10% can induce a near universal non-alcoholic steatohepatitis resolution and fibrosis improvement by at least one stage. However, modest weight loss (>5%) can also produce important benefits on the components of the NAFLD activity score (NAS). Additionally, we need to explore the role of total calories and type of weight loss diet, micro- and macronutrients, evidence-based benefits of physical activity and exercise and finally support these modifications through established behavioural change models and techniques for long-term maintenance of lifestyle modifications. Following a Mediterranean diet can reduce liver fat even without weight loss and is the most recommended dietary pattern for NAFLD. The Mediterranean diet is characterised by reduced carbohydrate intake, especially sugars and refined carbohydrates (40% of the calories vs. 50-60% in a typical low fat diet), and increased monounsaturated and omega-3 fatty acid intake (40% of the calories as fat vs. up-to 30% in a typical low fat diet). Both TV sitting (a reliable marker of overall sedentary behaviour) and physical activity are associated with cardio-metabolic health, NAFLD and overall mortality. A 'triple hit behavioural phenotype' of: i) sedentary behaviour, ii) low physical activity, and iii) poor diet have been defined. Clinical evidence strongly supports the role of lifestyle modification as a primary therapy for the management of NAFLD and NASH. This should be accompanied by the implementation of strategies to avoid relapse and weight regain.
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Affiliation(s)
- Manuel Romero-Gómez
- Mac.Ro UCM IC Digestive Diseases and Ciberehd, University Hospital Virgen del Rocio, Institute of Biomedicine of Seville, University of Seville, Sevilla, Spain.
| | - Shira Zelber-Sagi
- Department Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
| | - Michael Trenell
- NIHR Innovation Observatory, Newcastle University, Newcastle, UK
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11
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Dunn MA, Josbeno DA, Schmotzer AR, Tevar AD, DiMartini AF, Landsittel DP, Delitto A. The gap between clinically assessed physical performance and objective physical activity in liver transplant candidates. Liver Transpl 2016; 22:1324-32. [PMID: 27348200 DOI: 10.1002/lt.24506] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 06/01/2016] [Accepted: 06/19/2016] [Indexed: 12/13/2022]
Abstract
Frailty with sarcopenia in cirrhosis causes liver transplant wait-list attrition and deaths. Regular physical activity is needed to protect patients with cirrhosis from frailty. We subjectively assess physical performance in selecting patients for transplant listing, but we do not know whether clinical assessments reflect the extent of activity patients actually perform. To investigate this question, 53 wait-listed patients self-assessed their performance of ordinary physical tasks using the Rosow-Breslau survey, and clinicians assessed their physical performance status with the Karnofsky index. We compared these assessments with actual activity measured using an accelerometer/thermal sensing armband worn from 4 to 7 days. We found that their measured activity was among the lowest reported in chronic disease, similar to that of patients with advanced chronic pulmonary disease or renal failure. Their percentages of waking hours spent in sedentary, light, and moderate-vigorous activity were 75.9% ± 18.9%, 18.9% ± 14.3%, and 4.9% ± 6.9%, respectively. Higher mean sedentary and lower mean moderate-vigorous activity was significantly associated with 9 wait-list deaths (P = 0.004). Compared with a range of 7000-13,000 steps/day in healthy adults, patients' mean steps/day were 3164 ± 2842. Both their activity percentage and step data were typical of other severely inactive populations. Neither their Rosow-Breslau scores (mean 2.3 ± 0.8, maximum 3.0) nor their Karnofsky scores (mean 79 ± 12, maximum 100) suggested major impairment or showed a correlation with patients' actual physical performance. In conclusion, physical activity in patients with cirrhosis wait-listed for transplantation is highly sedentary. Self-assessments and provider assessments of physical activity do not reliably indicate actual performance. Whether the gap between assessed and actual performance may be favorably modified by interventions to improve activity and ameliorate frailty merits further study. Liver Transplantation 22 1324-1332 2016 AASLD.
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Affiliation(s)
- Michael A Dunn
- Center for Liver Diseases, University of Pittsburgh, Pittsburgh, PA. .,Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
| | - Deborah A Josbeno
- Department of Physical Therapy, University of Pittsburgh, Pittsburgh, PA
| | - Amy R Schmotzer
- Center for Liver Diseases, University of Pittsburgh, Pittsburgh, PA.,Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA
| | - Amit D Tevar
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.,Department of Surgery, University of Pittsburgh, Pittsburgh, PA
| | - Andrea F DiMartini
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.,Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA
| | - Douglas P Landsittel
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.,Department of Medicine, University of Pittsburgh, Pittsburgh, PA
| | - Anthony Delitto
- Department of Physical Therapy, University of Pittsburgh, Pittsburgh, PA
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12
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Marchesini G, Petta S, Dalle Grave R. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice. Hepatology 2016; 63:2032-43. [PMID: 26663351 DOI: 10.1002/hep.28392] [Citation(s) in RCA: 224] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 12/06/2015] [Indexed: 12/12/2022]
Abstract
Fatty liver accumulation results from an imbalance between lipid deposition and removal, driven by the hepatic synthesis of triglycerides and de novo lipogenesis. The habitual diet plays a relevant role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), and both risky (e.g., fructose) and protective foods (Mediterranean diet) have been described, but the contribution of excess calories remains pivotal. Accordingly, weight loss is the most effective way to promote liver fat removal. Several controlled studies have confirmed that an intense approach to lifestyle changes, carried on along the lines of cognitive-behavior treatment, is able to attain the desired 7%-10% weight loss, associated with reduced liver fat, nonalcoholic steatohepatitis (NASH) remission, and also reduction of fibrosis. Even larger effects are reported after bariatric surgery-induced weight loss in NAFLD, where 80% of subjects achieve NASH resolution at 1-year follow-up. These results provide solid data to evaluate the safety and effectiveness of the pharmacological treatment of NASH. The battle against metabolic diseases, largely fueled by increased liver fat, needs a comprehensive approach to be successful in an obesiogenic environment. In this review, we will discuss the role of hepatic lipid metabolism, genetic background, diet, and physical activity on fatty liver. They are the basis for a lifestyle approach to NAFLD treatment. (Hepatology 2016;63:2032-2043).
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Affiliation(s)
- Giulio Marchesini
- Unit of Metabolic Diseases & Clinical Dietetics, "Alma Mater Studiorum" University, Bologna, Italy
| | - Salvatore Petta
- Di.Bi.M.I.S, Section of Gastroenterology, University of Palermo, Palermo, Italy
| | - Riccardo Dalle Grave
- Department of Eating and Weight Disorders, Villa Garda Hospital, Garda (VR), Italy
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13
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Lonardo A, Bellentani S, Argo CK, Ballestri S, Byrne CD, Caldwell SH, Cortez-Pinto H, Grieco A, Machado MV, Miele L, Targher G. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups. Dig Liver Dis 2015; 47:997-1006. [PMID: 26454786 DOI: 10.1016/j.dld.2015.08.004] [Citation(s) in RCA: 334] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 07/27/2015] [Accepted: 08/06/2015] [Indexed: 02/07/2023]
Abstract
An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups. We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published until May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidaemia", "familial heterozygous hypobetalipoproteinaemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms". We found that age, sex and ethnicity are major physiological modifiers of the risk of non-alcoholic fatty liver disease, along with belonging to "non-alcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolaemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of non-alcoholic fatty liver disease risk. Compared with these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of non-alcoholic fatty liver disease. A better understanding of the epidemiology of non-alcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.
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Affiliation(s)
| | - Amedeo Lonardo
- Internal Medicine and Outpatient Liver Clinic, NOCSAE Baggiovara, Azienda USL di Modena, Modena, Italy.
| | - Stefano Bellentani
- Internal Medicine and Outpatient Liver Clinic, NOCSAE Baggiovara, Azienda USL di Modena, Modena, Italy; Department of Gastroenterology and Endoscopy, NOCSE Baggiovara, Azienda USL di Modena Modena, Italy
| | | | - Stefano Ballestri
- Internal Medicine Pavullo Hospital, Azienda USL di Modena, Modena, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, University of Southampton, Southampton National Institute for Health Research Biomedical Research Centre, Southampton, UK
| | | | - Helena Cortez-Pinto
- Department of Gastroenterology, University Hospital of Santa Maria, Faculty of Medicine, Lisbon, Portugal
| | - Antonio Grieco
- Institute of Internal Medicine, Catholic University of Rome, Rome, Italy
| | - Mariana V Machado
- Department of Gastroenterology, University Hospital of Santa Maria, Faculty of Medicine, Lisbon, Portugal
| | - Luca Miele
- Institute of Internal Medicine, Catholic University of Rome, Rome, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy
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Lückhoff HK, Kruger FC, Kotze MJ. Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries. World J Hepatol 2015; 7:1192-1208. [PMID: 26019735 PMCID: PMC4438494 DOI: 10.4254/wjh.v7.i9.1192] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/18/2014] [Accepted: 04/02/2015] [Indexed: 02/06/2023] Open
Abstract
Heterogeneity in clinical presentation, histological severity, prognosis and therapeutic outcomes characteristic of non-alcoholic fatty liver disease (NAFLD) necessitates the development of scientifically sound classification schemes to assist clinicians in stratifying patients into meaningful prognostic subgroups. The need for replacement of invasive liver biopsies as the standard method whereby NAFLD is diagnosed, graded and staged with biomarkers of histological severity injury led to the development of composite prognostic models as potentially viable surrogate alternatives. In the present article, we review existing scoring systems used to (1) confirm the presence of undiagnosed hepatosteatosis; (2) distinguish between simple steatosis and NASH; and (3) predict advanced hepatic fibrosis, with particular emphasis on the role of NAFLD as an independent cardio-metabolic risk factor. In addition, the incorporation of functional genomic markers and application of emerging imaging technologies are discussed as a means to improve the diagnostic accuracy and predictive performance of promising composite models found to be most appropriate for widespread clinical adoption.
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Ballestri S, Romagnoli D, Nascimbeni F, Francica G, Lonardo A. Role of ultrasound in the diagnosis and treatment of nonalcoholic fatty liver disease and its complications. Expert Rev Gastroenterol Hepatol 2015; 9:603-27. [PMID: 25694178 DOI: 10.1586/17474124.2015.1007955] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
We review the role of liver ultrasonography (US) and related techniques as non-invasive tools in predicting metabolic derangements, liver histology, portal hypertension and cardiovascular risk as well as allowing early diagnosis and management of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease. In this setting, US detects fatty changes as low as ≥20% and hepatic steatosis identified ultrasonographically, in its turn, closely mirrors coronary and carotid atherosclerosis burden. Semi-quantitative US indices (to exclude nonalcoholic steatohepatitis) and sonoelastography (to quantify fibrosis) help in predicting liver histology and selecting patients to submit to liver biopsy. Surveillance for hepatocellular carcinoma conducted through biannual US is mandatory and US has a role in guiding locoregional treatment and in evaluating the efficacy of treatment. High-intensity focused ultrasound can be delivered with precision resulting in coagulative necrosis of hepatocellular carcinoma without puncturing the liver. Costs and inconveniences have so far hampered its diffusion.
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Affiliation(s)
- Stefano Ballestri
- Division of Internal Medicine, Hospital of Pavullo - Department of Internal Medicine, Azienda USL, Pavullo, Modena 41126, Italy
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16
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Chen S, Zhao X, Ran L, Wan J, Wang X, Qin Y, Shu F, Gao Y, Yuan L, Zhang Q, Mi M. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Dig Liver Dis 2015; 47:226-32. [PMID: 25577300 DOI: 10.1016/j.dld.2014.11.015] [Citation(s) in RCA: 233] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Revised: 11/19/2014] [Accepted: 11/30/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease is a major health problem worldwide. Resveratrol is a natural polyphenol found in edible plants that has a variety of biochemical and physiological effects. AIMS To evaluate the effect of resveratrol on insulin resistance, glucose and lipid metabolism in non-alcoholic fatty liver disease. METHODS Double-blind, randomized, placebo-controlled trial: 60 subjects with non-alcoholic fatty liver disease were given 2 placebo capsules (placebo group) or 2 150mg resveratrol capsules (resveratrol group) twice daily for three months. Liver ultrasound imaging, anthropometric profile, serum liver enzymes, insulin, glucose, C-peptide, lipid profile, and inflammation-related cytokines were compared pre and post-treatment. RESULTS Compared with the placebo group, resveratrol significantly decreased aspartate aminotransferase, glucose and low-density lipoprotein cholesterol [-6.00 (-9.00, -3.00) IU/L, -0.64±0.31mmol/L, and -0.41±0.35mmol/L, respectively, P≤0.001] alanine aminotransferase, total cholesterol [-7.00 (-11.0, -2.50) IU/L and -0.67±0.50mmol/L, respectively, P=0.002], and homeostasis model assessment insulin resistance index (-0.60±1.15, P=0.016). In the resveratrol group significant reductions of the levels of tumour necrosis factor-alpha, cytokeratin 18 fragment, and fibroblast growth factor 21 [-0.53±1.30pg/mL, -26.9 (-70.3, 5.12) IU/L and -23.3 (-43.0, 0.31) pg/mL, respectively, P<0.05] and elevation of adiponectin level [1.22 (-0.37, 1.60) ng/mL, P=0.025] were observed. CONCLUSION Resveratrol supplementation may benefit patients with non-alcoholic fatty liver disease.
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Affiliation(s)
- Shihui Chen
- Research Center of Nutrition and Food Safety, The Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China
| | - Xiaolan Zhao
- Health Care Center of Southwest Hospital, The First Affiliated Hospital of The Third Military Medical University, Chongqing, China
| | - Li Ran
- Research Center of Nutrition and Food Safety, The Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China
| | - Jing Wan
- Research Center of Nutrition and Food Safety, The Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China
| | - Xiaofang Wang
- Health Care Center of Southwest Hospital, The First Affiliated Hospital of The Third Military Medical University, Chongqing, China
| | - Yu Qin
- Research Center of Nutrition and Food Safety, The Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China
| | - Furong Shu
- Research Center of Nutrition and Food Safety, The Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China
| | - Yanxiang Gao
- Research Center of Nutrition and Food Safety, The Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China
| | - Lijia Yuan
- Research Center of Nutrition and Food Safety, The Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China
| | - Qianyong Zhang
- Research Center of Nutrition and Food Safety, The Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.
| | - Mantian Mi
- Research Center of Nutrition and Food Safety, The Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.
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Toni S, Morandi R, Busacchi M, Tardini L, Merlini L, Battistini NC, Pellegrini M. Nutritional status evaluation in patients affected by bethlem myopathy and ullrich congenital muscular dystrophy. Front Aging Neurosci 2014; 6:315. [PMID: 25477818 PMCID: PMC4235079 DOI: 10.3389/fnagi.2014.00315] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Accepted: 10/26/2014] [Indexed: 01/26/2023] Open
Abstract
Collagen VI mutations lead to disabling myopathies like Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). We have investigated the nutritional and metabolic status of one UCMD and seven BM patients (five female, three male, mean age 31 ± 9 years) in order to find a potential metabolic target for nutritional intervention. For this study, we used standard anthropometric tools, such as BMI evaluation and body circumference measurements. All results were compared to dual-energy X-ray absorptiometry (DXA), considered the “gold standard” method. Energy intake of each patient was evaluated through longitudinal methods (7-day food diary) while resting energy expenditure (REE) was predicted using specific equations and measured by indirect calorimetry. Clinical evaluation included general and nutritional blood and urine laboratory analyses and quantitative muscle strength measurement by hand-held dynamometry. BM and UCMD patients showed an altered body composition, characterized by low free fat mass (FFM) and high fat mass (FM), allowing us to classify them as sarcopenic, and all but one as sarcopenic-obese. Another main result was the negative correlation between REE/FFM ratio (basal energy expenditure per kilograms of fat-free mass) and the severity of the disease, as defined by the muscle megascore (correlation coefficient −0.955, P-value <0.001). We postulate that the increase of the REE/FFM ratio in relation to the severity of the disease may be due to an altered and pathophysiological loss of energetic efficiency at the expense of skeletal muscle. We show that a specific metabolic disequilibrium is related to the severity of the disease, which may represent a target for a nutritional intervention in these patients.
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Affiliation(s)
- Silvia Toni
- Laboratory of Nutrition and Lifestyle, Department of Diagnostic, Clinical and Public Health Medicine , Modena , Italy
| | - Riccardo Morandi
- Laboratory of Nutrition and Lifestyle, Department of Diagnostic, Clinical and Public Health Medicine , Modena , Italy
| | - Marcello Busacchi
- Laboratory of Nutrition and Lifestyle, Department of Diagnostic, Clinical and Public Health Medicine , Modena , Italy
| | - Lucia Tardini
- Laboratory of Nutrition and Lifestyle, Department of Diagnostic, Clinical and Public Health Medicine , Modena , Italy
| | - Luciano Merlini
- Laboratory of Musculoskeletal Cell Biology, Istituto Ortopedico Rizzoli , Bologna , Italy
| | - Nino Carlo Battistini
- Laboratory of Nutrition and Lifestyle, Department of Diagnostic, Clinical and Public Health Medicine , Modena , Italy
| | - Massimo Pellegrini
- Laboratory of Nutrition and Lifestyle, Department of Diagnostic, Clinical and Public Health Medicine , Modena , Italy
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18
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Bertolotti M, Lonardo A, Mussi C, Baldelli E, Pellegrini E, Ballestri S, Romagnoli D, Loria P. Nonalcoholic fatty liver disease and aging: Epidemiology to management. World J Gastroenterol 2014; 20:14185-14204. [PMID: 25339806 PMCID: PMC4202348 DOI: 10.3748/wjg.v20.i39.14185] [Citation(s) in RCA: 208] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 02/17/2014] [Accepted: 06/17/2014] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients.
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Arab JP, Candia R, Zapata R, Muñoz C, Arancibia JP, Poniachik J, Soza A, Fuster F, Brahm J, Sanhueza E, Contreras J, Cuellar MC, Arrese M, Riquelme A. Management of nonalcoholic fatty liver disease: an evidence-based clinical practice review. World J Gastroenterol 2014; 20:12182-201. [PMID: 25232252 PMCID: PMC4161803 DOI: 10.3748/wjg.v20.i34.12182] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Revised: 03/27/2014] [Accepted: 04/27/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To build a consensus among Chilean specialists on the appropriate management of patients with nonalcoholic fatty liver disease (NAFLD) in clinical practice. METHODS NAFLD has now reached epidemic proportions worldwide. The optimal treatment for NAFLD has not been established due to a lack of evidence-based recommendations. An expert panel of members of the Chilean Gastroenterological Society and the Chilean Hepatology Association conducted a structured analysis of the current literature on NAFLD therapy. The quality of the evidence and the level of recommendations supporting each statement were assessed according to the recommendations of the United States Preventive Services Task Force. A modified three-round Delphi technique was used to reach a consensus among the experts. RESULTS A group of thirteen experts was established. The survey included 17 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 93.8% in the first round and 100% in the second and third rounds. The final recommendations support the indication of lifestyle changes, including diet and exercise, for all patients with NAFLD. Proven pharmacological therapies include only vitamin E and pioglitazone, which can be used in nondiabetic patients with biopsy-proven nonalcoholic steatohepatitis (the progressive form of NAFLD), although the long-term safety and efficacy of these therapies have not yet been established. CONCLUSION Current NAFLD management is rapidly evolving, and new pathophysiology-based therapies are expected to be introduced in the near future. All NAFLD patients should be evaluated using a three-focused approach that considers the risks of liver disease, diabetes and cardiovascular events.
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20
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Rosso N, Chavez-Tapia NC, Tiribelli C, Bellentani S. Translational approaches: From fatty liver to non-alcoholic steatohepatitis. World J Gastroenterol 2014; 20:9038-9049. [PMID: 25083077 PMCID: PMC4112858 DOI: 10.3748/wjg.v20.i27.9038] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2013] [Revised: 12/04/2013] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
Over the past few decades, non-alcoholic fatty liver disease (NAFLD) has become one, if not the most common, cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.
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21
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Kani AH, Alavian SM, Esmaillzadeh A, Adibi P, Azadbakht L. Effects of a novel therapeutic diet on liver enzymes and coagulating factors in patients with non-alcoholic fatty liver disease: A parallel randomized trial. Nutrition 2014; 30:814-21. [PMID: 24984998 DOI: 10.1016/j.nut.2013.11.008] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2013] [Revised: 11/25/2013] [Accepted: 11/25/2013] [Indexed: 01/27/2023]
Abstract
OBJECTIVE There are several reports regarding the role of therapeutic diets for patients with non-alcoholic fatty liver disease (NAFLD). Therefore, the aim of this study was to determine the effects of a low-calorie, low-carbohydrate soy-containing diet on lipid profiles, liver enzymes, and coagulating factors in patients with NAFLD. METHOD This was a randomized parallel clinical trial involving 45 patients with NAFLD. The participants consumed three kinds of diets for 8 wk. Patients were randomly assigned to consume a low-calorie diet; a low-calorie, low-carbohydrate diet; or a low-calorie, low-carbohydrate soy-containing diet. Measurements were done according to the standard method. RESULTS Changes in weight were not significantly different in the three groups. The low-calorie, low-carbohydrate soy-containing diet could reduce alanine aminotransferase (-15.2 ± 12.1 versus -6.8 ± 4.6 in the low-calorie, low-carbohydrate diet, and -6.4 ± 4.4 IU/L in the low-calorie diet; P = 0.02) and serum fibrinogen levels (-49.1 ± 60.1 versus -12.9 ± 8.1 and -17.4 ± 8.4 g/L, respectively; P = 0.01). Reductions in aspartate aminotransferase were significantly higher in the low-calorie, low-carbohydrate soy-containing group. Changes in lipid profiles did not differ significantly between the groups. The soy-containing diet did reduce malondialdehyde more than the other diets (P = 0.01). CONCLUSION A low-calorie, low-carbohydrate soy-containing diet could have beneficial effects on liver enzymes, malondialdehyde, and serum fibrinogen levels in patients with NAFLD.
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Affiliation(s)
- Ali Hashemi Kani
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ahmad Esmaillzadeh
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Peyman Adibi
- Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Leila Azadbakht
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the liver disease of this century, increasing in parallel with obesity, insulin resistance and the metabolic syndrome. NAFLD can be seen as a component of the metabolic syndrome, and as such, contributing as a risk factor for cardiovascular disease. In fact, these patients die more often from cardiovascular disease than from direct consequences of liver disease. In this review, we will summarize the data that link NAFLD as a central player in this dysmetabolism, as well as the evidence for appropriate therapy, in order to improve not only liver disease prognosis, but also the overall prognosis and risk of mortality, with particular focus on cardiovascular risk.
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Affiliation(s)
- Mariana Verdelho Machado
- Departamento de Gastrenterologia, Hospital Santa Maria, CHLN, Unidade de Nutrição e Metabolismo, Faculdade de Medicina de Lisboa, IMM, Lisbon, Portugal
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Marzuillo P, Miraglia del Giudice E, Santoro N. Pediatric fatty liver disease: Role of ethnicity and genetics. World J Gastroenterol 2014; 20:7347-7355. [PMID: 24966605 PMCID: PMC4064080 DOI: 10.3748/wjg.v20.i23.7347] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 01/04/2014] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.
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Wang S, Kuang X, Fang Z, Huang Z, Shi P. Effect of oleic acid on the levels of eight metal ions in human hepatoma SMMC-7721 cells. Biol Trace Elem Res 2014; 159:445-50. [PMID: 24867776 DOI: 10.1007/s12011-014-0018-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 05/14/2014] [Indexed: 10/25/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Its incidence is rising worldwide. However, no specific therapy has been shown to be effective in its treatment. In the present study, the in vitro NAFLD model was established in human SMMC-7721 cells by using oleic acid (OA). Then, content changes of eight cations, including sodium, magnesium, potassium, calcium, iron, copper, zinc, and manganese, were investigated in the experimental model. The results showed that OA induced a decrease in magnesium level, while an increase in iron one. Additionally, the supplementation of magnesium in the cell culture model was studied. It showed that magnesium ameliorated lipid accumulation induced by OA. Our results suggest that magnesium could decrease the risk of NAFLD and be used as a promising candidate for the treatment of NAFLD.
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Affiliation(s)
- Song Wang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
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Swinnen TW, Scheers T, Lefevre J, Dankaerts W, Westhovens R, de Vlam K. Physical activity assessment in patients with axial spondyloarthritis compared to healthy controls: a technology-based approach. PLoS One 2014; 9:e85309. [PMID: 24586239 PMCID: PMC3938397 DOI: 10.1371/journal.pone.0085309] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 11/25/2013] [Indexed: 01/21/2023] Open
Abstract
Introduction Traditionally, assessment in axial Spondyloarthritis (aSpA) includes the evaluation of the capacity to execute tasks, conceptualized as physical function. The role of physical activity, defined as movement-related energy expenditure, is largely unknown and almost exclusively studied using patient-reported outcome measures. The aims of this observational cross-sectional study are to compare physical activity between patients with aSpA and healthy controls (HC) and to evaluate the contribution of disease activity to physical activity differences between groups. Methods Forty patients with aSpA were matched by age, gender, period of data acquisition in terms of days and season to 40 HC. Physical activity was measured during five consecutive days (three weekdays and two weekend days) using ambulatory monitoring (SenseWear Armband). Self-reported disease activity was measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Differences in physical activity between patients with aSpA and HC were examined with Wilcoxon signed-rank tests and a mixed linear model. Difference scores between patients and HC were correlated with disease activity. Results Average weekly physical activity level (Med(IQR); HC:1.54(1.41–1.73); aSpA:1.45(1.31–1.67),MET) and energy expenditure (HC:36.40(33.43–41.01); aSpA:34.55(31.08–39.41),MET.hrs/day) were significantly lower in patients with aSpA. Analyses across intensity levels revealed no significant differences between groups for inactivity and time spent at light or moderate physical activities. In contrast, weekly averages of vigorous (HC:4.02(1.20–12.60); aSpA:0.00(0.00–1.20),min/d), very vigorous physical activities (HC0.00(0.00–1.08); aSpA:0.00(0.00–0.00),mind/d) and moderate/(very)vigorous combined (HC2.41(1.62–3.48); aSpA:1.63(1.20–2.82),hrs/d) were significantly lower in patients with aSpA. Disease activity did not interact with differences in physical activity between patients with aSpA and HC, evidenced by non-significant and very low correlations (range: −0.06–0.17) between BASDAI and HC-aSpA patients' difference scores. Conclusions Patients with aSpA exhibit lower physical activity compared to HC and these differences are independent of self-reported disease activity. Further research on PA in patients with aSpA should be prioritized.
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Affiliation(s)
- Thijs Willem Swinnen
- Rheumatology, University Hospitals Leuven, Leuven, Belgium
- Department of Development and Regeneration, KU Leuven, Leuven, Belgium
- Department of Rehabilitation Sciences, KU Leuven, Heverlee, Belgium
| | - Tineke Scheers
- Department of Kinesiology, KU Leuven, Heverlee, Belgium
- Research Foundation Flanders, Brussel, Belgium
| | - Johan Lefevre
- Department of Kinesiology, KU Leuven, Heverlee, Belgium
| | - Wim Dankaerts
- Department of Rehabilitation Sciences, KU Leuven, Heverlee, Belgium
| | - Rene Westhovens
- Rheumatology, University Hospitals Leuven, Leuven, Belgium
- Department of Development and Regeneration, KU Leuven, Leuven, Belgium
| | - Kurt de Vlam
- Rheumatology, University Hospitals Leuven, Leuven, Belgium
- Department of Development and Regeneration, KU Leuven, Leuven, Belgium
- * E-mail:
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Loria P, Marchesini G, Nascimbeni F, Ballestri S, Maurantonio M, Carubbi F, Ratziu V, Lonardo A. Cardiovascular risk, lipidemic phenotype and steatosis. A comparative analysis of cirrhotic and non-cirrhotic liver disease due to varying etiology. Atherosclerosis 2014; 232:99-109. [PMID: 24401223 DOI: 10.1016/j.atherosclerosis.2013.10.030] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 10/23/2013] [Accepted: 10/24/2013] [Indexed: 02/08/2023]
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Bradford V, Dillon J, Miller M. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease. ACTA ACUST UNITED AC 2013; 6:1-10. [PMID: 24826079 PMCID: PMC3953742 DOI: 10.2147/hmer.s34472] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The burden of non-alcoholic fatty liver disease (NAFLD) worldwide is a significant clinical and public health issue, affecting approximately one third of the Western population. This review assesses the effect and impact lifestyle interventions have on the treatment of this common condition. We review studies comparing the effect of calorie restriction and exercise programs, as well as comparison of lifestyle intervention with pharmaceutical intervention. Both calorie restriction and exercise programs are shown to be beneficial in improving features of metabolic syndrome and surrogate markers of NAFLD. The paucity of studies using histological improvement hinders the ability to conclude a benefit on improvement of histological NAFLD, although this is shown in a small number of studies. There is a need to extend the intervention period to show a sustained improvement with intervention as most studies have a follow up period of 12 months of less.
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Affiliation(s)
- V Bradford
- MH Miller, Gut Group, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland
| | - Jf Dillon
- MH Miller, Gut Group, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland
| | - Mh Miller
- MH Miller, Gut Group, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland
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Rusu E, Jinga M, Enache G, Rusu F, Dragomir AD, Ancuta I, Draguţ R, Parpala C, Nan R, Sima I, Ateia S, Stoica V, Cheţa DM, Radulian G. Effects of lifestyle changes including specific dietary intervention and physical activity in the management of patients with chronic hepatitis C--a randomized trial. Nutr J 2013; 12:119. [PMID: 23941362 PMCID: PMC3751456 DOI: 10.1186/1475-2891-12-119] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Accepted: 08/07/2013] [Indexed: 01/06/2023] Open
Abstract
Background In patients with chronic hepatitis C (CHC), obesity is involved in the pathogenesis of insulin resistance, fatty liver disease and progression of fibrosis. The objective of this study was to compare a normoglucidic low-calorie diet (NGLCD) with a low-fat diet (LFD) among participants with CHC. Aimed to measure the impact of dietary changes in reduction of insulin resistance, obesity but also in steatosis and fibrosis. Methods Randomized, controlled trial in three medical centers with assessments at baseline, 6 months and 12 months. Participants were patients over 35 years with chronic hepatitis C (n = 120) with BMI over 25 kg/m2. We evaluated the effects of NGLCD vs. LFD in weight management and metabolic improvement. The primary endpoint was to measure the impact of dietary changes through nutritional intervention in reversibility of insulin resistance, obesity, steatosis, and fibrosis. We performed anthropometric measurements, fasting glucose profile, serum lipids, liver profile, blood count at baseline, 6 and 12 months. Steatosis was evaluated using ultrasonographic criteria. Liver fibrosis was non-invasively assessed. Results After 6 and 12 months of intervention, both groups had a significant decrease in caloric consumption. At 6 months, weight loss was greater in the NGLCD group (−5.02 ± 3.43 kg vs. −4.1 ± 2.6 kg; p = 0.002) compared to the LFD group. At 1-year, however, weight loss was similar in both groups (−3.9 ± 3.3 kg vs. −3.1 ± 2.6 kg; p = 0.139). At 12 months, fasting plasma glucose, fasting plasma insulin, and HOMA-IR had significant improvements in both groups. With both diets aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) decreased with significant differences; also there were significant improvements in AST/ALT ratio, Forns fibrosis index. The two diets were associated with reduction of both the prevalence and the severity of steatosis (all p < 0.001). At 12 months, total cholesterol, HDL-cholesterol, triglycerides improved in both groups (all p < 0.05). Conclusions The present study establishes the benefits of low-calorie diet and low-fat diet in management of patients with hepatitis C regarding improvement of insulin resistance, steatosis and also fibrosis. Overweight or obese patients with CHC undergoing a lifestyle intervention (specific dietary intervention and physical activity) for 1-year had significant improvements in body weight, lipid and hepatic profile. Trial registration PNCI2-3343/41008/2007
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Affiliation(s)
- Emilia Rusu
- "Prof. N. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases-Bucharest, Romania
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