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Mikkelsen ACD, Kjærgaard K, Schapira AHV, Mookerjee RP, Thomsen KL. The liver-brain axis in metabolic dysfunction-associated steatotic liver disease. Lancet Gastroenterol Hepatol 2025; 10:248-258. [PMID: 39701123 DOI: 10.1016/s2468-1253(24)00320-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 09/25/2024] [Accepted: 09/26/2024] [Indexed: 12/21/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30% of the global population. Studies suggest that MASLD is associated with compromised brain health and cognitive dysfunction, initiating a growing interest in exploring the liver-brain axis mechanistically within MASLD pathophysiology. With the prevalence of MASLD increasing at an alarming rate, leaving a large proportion of people potentially at risk, cognitive dysfunction in MASLD is a health challenge that requires careful consideration and awareness. This Review summarises the current literature on cognitive function in people with MASLD and discusses plausible causes for its impairment. It is likely that a multifaceted spectrum of factors works collectively to affect cognition in patients with MASLD. We describe the role of inflammation, vascular disease, and brain ageing and neurodegeneration as possible key players. This Review also highlights the need for future studies to identify the optimal test for diagnosing cognitive dysfunction in patients with MASLD, to examine the correlation between MASLD progression and the severity of cognitive dysfunction, and to evaluate whether new MASLD-targeted therapies also improve brain dysfunction.
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Affiliation(s)
- Anne Catrine Daugaard Mikkelsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Kristoffer Kjærgaard
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Anthony H V Schapira
- Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, London, UK
| | - Rajeshwar P Mookerjee
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Institute for Liver and Digestive Health, University College London, London, UK
| | - Karen Louise Thomsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Institute for Liver and Digestive Health, University College London, London, UK.
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Sheptulina AF, Lyusina EO, Mamutova EM, Yafarova AA, Kiselev AR, Drapkina OM. Bioelectrical Impedance Analysis Demonstrates Reliable Agreement with Dual-Energy X-ray Absorptiometry in Identifying Reduced Skeletal Muscle Mass in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Hypertension. Diagnostics (Basel) 2024; 14:2301. [PMID: 39451624 PMCID: PMC11507167 DOI: 10.3390/diagnostics14202301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 09/24/2024] [Accepted: 10/15/2024] [Indexed: 10/26/2024] Open
Abstract
Background/Objectives: Body composition (BC) affects the risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertension (HTN). Currently, dual-energy X-ray absorptiometry (DEXA) is considered the gold standard for assessing BC, even though it has some limitations, including immobility, ionizing radiation, and patient weight restrictions. The aim of the study was to evaluate the correlations of BC parameters measured by bioelectrical impedance analysis (BIA) with those measured by DEXA in patients with MASLD and HTN. Methods: Overall, 78 patients with MASLD and HTN underwent the following study procedures: compilation of an anamnesis, physical examination of a patient, laboratory tests, abdominal ultrasound, BIA, DEXA, and anthropometric measurements. Results: The agreement between BIA and DEXA in diagnosing reduced skeletal muscle mass (SMM) in patients with MASLD and HTN was moderate (kappa values were 0.440 and 0.404 in males and females, respectively). Significant strong direct correlations were found between fat mass (FM) and body fat percentage measured by BIA with corresponding measurements by DEXA (p < 0.001 for both). The area under the receiver operating characteristic curves (AUC) of SMM to body weight ratios calculated using BIA data were 0.834 and 0.929 for reduced appendicular SMM determined by DEXA in males and females with MASLD and HTN, respectively. Conclusions: In conclusion, BIA is an easy-to-use and widely available tool for assessing SMM and FM in patients with MASLD and HTN, demonstrating reliable agreement with DEXA measurement results and completely free of its limitations.
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Affiliation(s)
- Anna F. Sheptulina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
| | - Ekaterina O. Lyusina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Elvira M. Mamutova
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Adel A. Yafarova
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Anton R. Kiselev
- Coordinating Center for Fundamental Research, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Oxana M. Drapkina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
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Younossi ZM, Kremer AE, Swain MG, Jones D, Bowlus C, Trauner M, Henry L, Gerber L. Assessment of fatigue and its impact in chronic liver disease. J Hepatol 2024; 81:726-742. [PMID: 38670320 DOI: 10.1016/j.jhep.2024.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/19/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024]
Abstract
Patient-reported outcomes (PROs), such as health-related quality of life (HRQL), are important outcome measures for patients with chronic liver diseases (CLDs). Presence of cirrhosis and advanced liver disease have been associated with worsened HRQL and fatigue. On the other hand, some patients with earlier stages of CLD also experience fatigue, causing PRO impairment. Treatment for some CLDs may improve HRQL and, sometimes, levels of fatigue. We aimed to provide an in-depth expert review of concepts related to fatigue and HRQL in patients with primary biliary cholangitis, hepatitis C virus and MASLD (metabolic dysfunction-associated steatotic liver disease). A panel of experts in fatigue and CLD reviewed and discussed the literature and collaborated to provide this expert review of fatigue in CLD. Herein, we review and report on the complexity of fatigue, highlighting that it is comprised of peripheral (neuromuscular failure, often in conjunction with submaximal cardiorespiratory function) and central (central nervous system dysfunction) causes. Fatigue and HRQL are measured using validated self-report instruments. Additionally, fatigue can be measured through objective tests (e.g. grip strength). Fatigue has deleterious effects on HRQL and one's ability to be physically active and socially engaged but does not always correlate with CLD severity. Treatments for hepatitis C virus and MASLD can improve levels of fatigue and HRQL, but current treatments for primary biliary cholangitis do not seem to affect levels of fatigue. We conclude that obtaining PRO data, including on HRQL and fatigue, is essential for determining the comprehensive burden of CLD and its potential treatments.
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Affiliation(s)
- Zobair M Younossi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA; The Global Liver Council, Washington DC, USA.
| | - Andreas E Kremer
- Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Mark G Swain
- Professor of Medicine, Cal Wenzel Family Foundation Chair in Hepatology, University of Calgary Liver Unit, Calgary, Canada
| | - David Jones
- Professor of Liver Immunology, Newcastle University, Newcastle upon Tyne, UK
| | - Christopher Bowlus
- Lena Valente Professor and Chief, Division of Gastroenterology and Hepatology, University of California Davis, United States
| | - Michael Trauner
- Div. of Gastroenterology & Hepatology, Dept. of Internal Medicine III, MedUni Wien, Medical University of Vienna, Austria
| | - Linda Henry
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA; The Global Liver Council, Washington DC, USA; Center for Outcomes Research in Liver Diseases, Washington DC, USA
| | - Lynn Gerber
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA; The Global Liver Council, Washington DC, USA
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Busebee B, Watt KD, Dupuy-McCauley K, DuBrock H. Sleep disturbances in chronic liver disease. Liver Transpl 2024; 30:1058-1071. [PMID: 38535627 DOI: 10.1097/lvt.0000000000000369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 03/15/2024] [Indexed: 05/03/2024]
Abstract
Sleep disturbances are common in chronic liver disease and significantly impact patient outcomes and quality of life. The severity and nature of sleep disturbances vary by liver disease etiology and severity. While there is ongoing research into the association between liver disease and sleep-wake dysfunction, the underlying pathophysiology varies and, in many cases, is poorly understood. Liver disease is associated with alterations in thermoregulation, inflammation, and physical activity, and is associated with disease-specific complications, such as HE, that may directly affect sleep. In this article, we review the relevant pathophysiologic processes, disease-specific sleep-wake disturbances, and clinical management of CLD-associated sleep-wake disturbances.
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Affiliation(s)
- Bradley Busebee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Kara Dupuy-McCauley
- Division of Pulmonology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Hilary DuBrock
- Division of Pulmonology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
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Henin G, Loumaye A, Deldicque L, Leclercq IA, Lanthier N. Unlocking liver health: Can tackling myosteatosis spark remission in metabolic dysfunction-associated steatotic liver disease? Liver Int 2024; 44:1781-1796. [PMID: 38623714 DOI: 10.1111/liv.15938] [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: 02/04/2024] [Revised: 03/12/2024] [Accepted: 04/02/2024] [Indexed: 04/17/2024]
Abstract
Myosteatosis is highly prevalent in metabolic dysfunction-associated steatotic liver disease (MASLD) and could reciprocally impact liver function. Decreasing muscle fat could be indirectly hepatoprotective in MASLD. We conducted a review to identify interventions reducing myosteatosis and their impact on liver function. Non-pharmacological interventions included diet (caloric restriction or lipid enrichment), bariatric surgery and physical activity. Caloric restriction in humans achieving a mean weight loss of 3% only reduces muscle fat. Lipid-enriched diet increases liver fat in human with no impact on muscle fat, except sphingomyelin-enriched diet which reduces both lipid contents exclusively in pre-clinical studies. Bariatric surgery, hybrid training (resistance exercise and electric stimulation) or whole-body vibration in human decrease both liver and muscle fat. Physical activity impacts both phenotypes by reducing local and systemic inflammation, enhancing insulin sensitivity and modulating the expression of key mediators of the muscle-liver-adipose tissue axis. The combination of diet and physical activity acts synergistically in liver, muscle and white adipose tissue, and further decrease muscle and liver fat. Several pharmacological interventions (patchouli alcohol, KBP-089, 2,4-dinitrophenol methyl ether, adipoRon and atglistatin) and food supplementation (vitamin D or resveratrol) improve liver and muscle phenotypes in pre-clinical studies by increasing fatty acid oxidation and anti-inflammatory properties. These interventions are effective in reducing myosteatosis in MASLD while addressing the liver disease itself. This review supports that disturbances in inter-organ crosstalk are key pathophysiological mechanisms involved in MASLD and myosteatosis pathogenesis. Focusing on the skeletal muscle might offer new therapeutic strategies to treat MASLD by modulating the interactions between liver and muscles.
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Affiliation(s)
- Guillaume Henin
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
- Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Audrey Loumaye
- Service d'Endocrinologie, Diabétologie et Nutrition, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | | | - Isabelle A Leclercq
- Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Nicolas Lanthier
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
- Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium
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Du X, Hu J, Xue J, Zhuang Y, Tang X, Xu Z. Rate and Associated Factors of Fatigue in Chinese Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Survey. Int J Gen Med 2024; 17:2945-2953. [PMID: 38984071 PMCID: PMC11231026 DOI: 10.2147/ijgm.s466980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 06/25/2024] [Indexed: 07/11/2024] Open
Abstract
Purpose Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients' quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients. Patients and Methods A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t-tests, χ2 tests and logistic regression models. Results We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue. Conclusion This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life.
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Affiliation(s)
- Xian Du
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
| | - Jun Hu
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
| | - Jianhua Xue
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
| | - Yuan Zhuang
- The Affiliated Hospital of Nantong University, Nantong, People's Republic of China
| | - Xuefeng Tang
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
| | - Zhiyue Xu
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
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Takano K, Kaneda M, Aoki Y, Fujita N, Chiba S, Michihara S, Han LK, Takahashi R. The protective effects of Ninjin'yoeito against liver steatosis/fibrosis in a non-alcoholic steatohepatitis model mouse. J Nat Med 2024; 78:514-524. [PMID: 38498120 PMCID: PMC11101552 DOI: 10.1007/s11418-024-01786-2] [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: 08/07/2023] [Accepted: 02/01/2024] [Indexed: 03/20/2024]
Abstract
Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic form of non-alcoholic fatty liver disease. Liver fibrosis leads to liver cancer and cirrhosis, and drug therapy for NASH remains lacking. Ninjin'yoeito (NYT) has shown antifibrotic effects in a model of liver fibrosis without steatosis but has not been studied for NASH. Therefore, we evaluated the efficacy of NYT in mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) as a NASH model. Compared with the normal diet group, mice fed CDAHFD showed decreased body weight and increased white adipose tissue, liver weight, and triglyceride content in the liver. Furthermore, a substantial increase in the hepatic concentration of hydroxyproline, expression of α-smooth muscle actin (α-SMA), and transforming growth factor-β was observed in CDAHFD-fed mice. Masson's trichrome and Picro-Sirius red staining revealed a remarkable increase in collagen fiber compared with the normal diet group. Compared with mice that received CDAHFD alone, those supplemented with NYT exhibited reduced hepatic triglyceride and hydroxyproline levels and α-SMA expression. Additionally, compared with the group fed CDAHFD alone, the stained liver tissues of NYT-treated mice exhibited a reduction in Masson's trichrome- and Picro-Sirius red-positive areas. Locomotor activity was significantly reduced in the CDAHFD-fed group compared with the normal diet group. In the NYT-treated group, the CDAHFD-induced decrease in locomotor activity was significantly suppressed. The findings indicate that NYT inhibited fatty and fibrotic changes in the livers of NASH mice and alleviated the decrease in locomotor activity. Therefore, NYT may serve as a novel therapeutic approach for NASH.
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Affiliation(s)
- Kyohei Takano
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan.
| | - Marisa Kaneda
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Yayoi Aoki
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Nina Fujita
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Shigeki Chiba
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Seiwa Michihara
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Li-Kun Han
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Ryuji Takahashi
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
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Funuyet-Salas J, Martín-Rodríguez A, Pérez-San-Gregorio MÁ, Vale L, Robinson T, Anstee QM, Romero-Gómez M. Health-related quality of life in non-alcoholic fatty liver disease: A cross-cultural study between Spain and the United Kingdom. PLoS One 2024; 19:e0300362. [PMID: 38709751 PMCID: PMC11073709 DOI: 10.1371/journal.pone.0300362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 02/24/2024] [Indexed: 05/08/2024] Open
Abstract
BACKGROUND It is unclear what biopsychosocial factors influence the impact of NAFLD on health-related quality of life (HRQoL), and if these factors are equally important predictors between different nationalities. METHODS HRQoL (CLDQ) was measured in both Southern European (Spain, n = 513) and Northern European (United Kingdom -UK-, n = 224) cohorts of patients with NAFLD in this cross-sectional study. For each cohort, participant data were recorded on histological grade of steatohepatitis, stage of fibrosis and biopsychosocial variables. Regression analysis was used to explore which of these variables predicted HRQoL. Moderated mediation models were conducted using SPSS PROCESS v3.5 macro. RESULTS Participants with severe fibrosis reported more fatigue, systemic symptoms and worry, and lower HRQoL than those with none/mild fibrosis, regardless of place of origin. In addition, body mass index (BMI) and gender were found to be significant predictors of HRQoL in both Spanish and UK participants. Female gender was associated with worse emotional function, higher BMI and more fatigue, which predicted lower participants' HRQoL. UK participants showed more systemic symptoms and worry than Spanish participants, regardless of liver severity. The negative effects of gender on HRQoL through emotional function, BMI and fatigue were reported to a greater degree in UK than in Spanish participants. CONCLUSIONS UK participants showed a greater impairment in HRQoL as compared to Spanish participants. Higher fibrosis stage predicted lower HRQoL, mainly in the Spanish cohort. Factors such as female gender or higher BMI contributed to the impact on HRQoL in both cohorts of patients and should be considered in future multinational intervention studies in NAFLD.
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Affiliation(s)
| | - Agustín Martín-Rodríguez
- Faculty of Psychology, Department of Personality, Assessment, and Psychological Treatment, University of Seville, Seville, Spain
| | - María Ángeles Pérez-San-Gregorio
- Faculty of Psychology, Department of Personality, Assessment, and Psychological Treatment, University of Seville, Seville, Spain
| | - Luke Vale
- Faculty of Medical Sciences, Population Health Sciences Institute, Health Economics Group, Newcastle University, Newcastle upon Tyne, United Kingdom
- National Institute for Health Research (NIHR) Newcastle In Vitro Diagnostics Co-Operative and NIHR Applied Research Collaboration North East and North Cumbria, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Tomos Robinson
- Faculty of Medical Sciences, Population Health Sciences Institute, Health Economics Group, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Quentin M. Anstee
- Faculty of Medical Sciences, Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
- Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
| | - Manuel Romero-Gómez
- Institute of Biomedicine of Seville, UCM Digestive Diseases and Ciberehd, Virgen del Rocío University Hospital, University of Seville, Seville, Spain
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Shea S, Lionis C, Kite C, Lagojda L, Uthman OA, Dallaway A, Atkinson L, Chaggar SS, Randeva HS, Kyrou I. Non-alcoholic fatty liver disease and coexisting depression, anxiety and/or stress in adults: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2024; 15:1357664. [PMID: 38689730 PMCID: PMC11058984 DOI: 10.3389/fendo.2024.1357664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 03/22/2024] [Indexed: 05/02/2024] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, affecting 25-30% of the general population globally. The condition is even more prevalent in individuals with obesity and is frequently linked to the metabolic syndrome. Given the known associations between the metabolic syndrome and common mental health issues, it is likely that such a relationship also exists between NAFLD and mental health problems. However, studies in this field remain limited. Accordingly, the aim of this systematic review and meta-analysis was to explore the prevalence of one or more common mental health conditions (i.e., depression, anxiety, and/or stress) in adults with NAFLD. Methods PubMed, EBSCOhost, ProQuest, Ovid, Web of Science, and Scopus were searched in order to identify studies reporting the prevalence of depression, anxiety, and/or stress among adults with NAFLD. A random-effects model was utilized to calculate the pooled prevalence and confidence intervals for depression, anxiety and stress. Results In total, 31 studies were eligible for inclusion, involving 2,126,593 adults with NAFLD. Meta-analyses yielded a pooled prevalence of 26.3% (95% CI: 19.2 to 34) for depression, 37.2% (95% CI: 21.6 to 54.3%) for anxiety, and 51.4% (95% CI: 5.5 to 95.8%) for stress among adults with NAFLD. Conclusion The present findings suggest a high prevalence of mental health morbidity among adults with NAFLD. Given the related public health impact, this finding should prompt further research to investigate such associations and elucidate potential associations between NAFLD and mental health morbidity, exploring potential shared underlying pathophysiologic mechanisms. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42021288934.
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Affiliation(s)
- Sue Shea
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
| | - Christos Lionis
- Laboratory of “Health and Science” School of Medicine, University of Crete, Heraklion, Greece
- Department of Health, Medicine and Caring Sciences, University of Linkoping, Linkoping, Sweden
- Department of Nursing, Frederick University, Nicosia, Cyprus
| | - Chris Kite
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- School of Health and Society, Faculty of Education, Health and Wellbeing, University of Wolverhampton, Wolverhampton, United Kingdom
- Chester Medical School, University of Chester, Shrewsbury, United Kingdom
- Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry, United Kingdom
| | - Lukasz Lagojda
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Clinical Evidence-Based Information Service (CEBIS), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
| | - Olalekan A. Uthman
- Division of Health Sciences, Warwick Centre for Global Health, Warwick Medical School, University of Warwick, Coventry, United Kingdom
| | - Alexander Dallaway
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- School of Health and Society, Faculty of Education, Health and Wellbeing, University of Wolverhampton, Wolverhampton, United Kingdom
| | - Lou Atkinson
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- iPrescribe Exercise Digital Ltd (EXI), London, United Kingdom
| | | | - Harpal S. Randeva
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry, United Kingdom
- Institute of Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
| | - Ioannis Kyrou
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry, United Kingdom
- Institute of Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham, United Kingdom
- College of Health, Psychology and Social Care, University of Derby, Derby, United Kingdom
- Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, Athens, Greece
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Drapkina OM, Martynov AI, Arutyunov GP, Bakulin IG, Livzan MA, Maev IV, Egorov IV. Resolution of the Expert Forum "New therapeutic horizons of NAFLD". TERAPEVT ARKH 2024; 96:186-193. [DOI: 10.26442/00403660.2024.02.202648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Aim. To present the materials of the Expert Forum "New therapeutic horizons of NAFLD," held on December 19, 2023, on the updated nomenclature of fatty liver disease (FLD), its main issues of diagnosis and treatment, the burden of cardiovascular risk in FLD patients. Executive Summary of the Resolution. It is recommended that the latest update of the FLD nomenclature be considered for adaptation to the clinical practice of doctors of all therapeutic specialties. Due to the high prevalence of a combination of non-alcoholic fatty liver disease (NAFLD) and an alcoholic component in the Russian Federation, it is essential to distinguish this subgroup of patients. Numerous clinical conditions associated with NAFLD include cardiovascular disease, pre-diabetes/type 2 diabetes mellitus, polycystic ovary syndrome, obstructive sleep apnea, sarcopenic obesity, cholelithiasis, and chronic kidney disease. Once a diagnosis of NAFLD has been made, further examination of patients should be aimed at detecting the presence of fibrosis using non-invasive methods such as transient liver elastography, FibroTest, and calculation of the FIB-4 fibrosis index. The original ademethionine can be considered a universal drug in treating NAFLD due to reducing oxidative stress and correcting concomitant fatigue and asthenia.
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11
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Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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12
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Noll A, Sadjadi R. The pharmacology of exercise: Strategies and challenges in the optimization of functional status in cirrhosis. Clin Liver Dis (Hoboken) 2024; 23:e0165. [PMID: 38681515 PMCID: PMC11049771 DOI: 10.1097/cld.0000000000000165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 03/01/2024] [Indexed: 05/01/2024] Open
Affiliation(s)
- Alan Noll
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Raha Sadjadi
- Division of Gastroenterology and Hepatology, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA
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13
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Niezen S, Noll A, Bamporiki J, Rogal SS. Management of fatigue and sleep disorders in patients with chronic liver disease. Clin Liver Dis (Hoboken) 2024; 23:e0122. [PMID: 38911999 PMCID: PMC11191865 DOI: 10.1097/cld.0000000000000122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 12/06/2023] [Indexed: 06/25/2024] Open
Affiliation(s)
- Sebastian Niezen
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Alan Noll
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Judith Bamporiki
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Shari S. Rogal
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
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14
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Eskridge W, Cryer DR, Schattenberg JM, Gastaldelli A, Malhi H, Allen AM, Noureddin M, Sanyal AJ. Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: The Patient and Physician Perspective. J Clin Med 2023; 12:6216. [PMID: 37834859 PMCID: PMC10573476 DOI: 10.3390/jcm12196216] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 09/19/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023] Open
Abstract
Diagnosing and managing metabolic dysfunction-associated steatotic liver disease (MASLD) remains a major challenge in primary care due to lack of agreement on diagnostic tools, difficulty in identifying symptoms and determining their cause, absence of approved pharmacological treatments, and limited awareness of the disease. However, prompt diagnosis and management are critical to preventing MASLD from progressing to more severe forms of liver disease. This highlights the need to raise awareness and improve understanding of MASLD among both patients and physicians. The patient perspective is invaluable to advancing our knowledge of this disease and how to manage it, as their perspectives have led to the growing recognition that patients experience subtle symptoms and that patient-reported outcomes should be incorporated into drug development. This review and expert opinion examine MASLD and metabolic dysfunction-associated steatohepatitis from the patient and physician perspective from pre-diagnosis to diagnosis and early care, through to progression to advanced liver damage. Specifically, the paper dives into the issues patients and physicians experience, and, in turn, what is required to improve diagnosis and management, including tips and tools to empower patients and physicians dealing with MASLD.
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Affiliation(s)
| | | | - Jörn M. Schattenberg
- Metabolic Liver Research Program, Department of Medicine, University Medical Center of the Johannes Gutenberg University, 155131 Mainz, Germany
| | - Amalia Gastaldelli
- Cardiometabolic Risk Laboratory, Institute of Clinical Physiology, Italian National Research Council CNR, 00133 Pisa, Italy
| | - Harmeet Malhi
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55901, USA
| | - Alina M. Allen
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55901, USA
| | - Mazen Noureddin
- Fatty Liver Program, Karsh Division of Gastroenterology and Hepatology, Cedar Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Arun J. Sanyal
- Stravitz-Sanyal Institute of Liver Disease and Metabolic Health, VCU School of Medicine and Health System and Division of Gastroenterology, Department of Internal Medicine, VCU School of Medicine, Richmond, VA 23298, USA
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15
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Moghtadaie A, Mahboobi H, Fatemizadeh S, Kamal MA. Emerging role of nanotechnology in treatment of non-alcoholic fatty liver disease (NAFLD). EXCLI JOURNAL 2023; 22:946-974. [PMID: 38023570 PMCID: PMC10630531 DOI: 10.17179/excli2023-6420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 08/29/2023] [Indexed: 12/01/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a prevailing health challenge that requires urgent innovative interventions. This review explores the role of nanotechnology as a promising potential in the treatment of NAFLD. It delineates the limitations of the current management strategies for NAFLD and highlights the new nanotechnology-based treatments including nanoemulsions, liposomes, micelles, polymeric nanoparticles, nanogels, inorganic nanoparticles, and zinc oxide nanoparticles. Despite the optimism surrounding the nanotechnological approach, the review underscores the need to address the limitations such as technical challenges, potential toxicity, and ethical considerations that impede the practical application of nanotechnology in NAFLD management. It advocates for collaborative efforts from researchers, clinicians, ethicists, and policymakers to achieve safe, effective, and equitable nanotechnology-based treatments for NAFLD. See also Figure 1(Fig. 1).
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Affiliation(s)
- Atie Moghtadaie
- Clinical Fellow in Gastroenterology and Hepatology, Digestive Disease Research Institute, Department of Gastroenterology and Hepatology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Mahboobi
- Clinical Fellow in Gastroenterology and Hepatology, Digestive Disease Research Institute, Department of Gastroenterology and Hepatology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Somayeh Fatemizadeh
- Department of Gastroenterology and Hepatology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Amjad Kamal
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, China
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
- Enzymoics, 7 Peterlee place, Hebersham, NSW 2770; Novel Global Community Educational Foundation, Australia
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16
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Wegermann K, Fudim M, Henao R, Howe CF, McGarrah R, Guy C, Abdelmalek MF, Diehl AM, Moylan CA. Serum Metabolites Are Associated With HFpEF in Biopsy-Proven Nonalcoholic Fatty Liver Disease. J Am Heart Assoc 2023:e029873. [PMID: 37421270 PMCID: PMC10382080 DOI: 10.1161/jaha.123.029873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 06/05/2023] [Indexed: 07/10/2023]
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) share common risk factors, including obesity and diabetes. They are also thought to be mechanistically linked. The aim of this study was to define serum metabolites associated with HFpEF in a cohort of patients with biopsy-proven NAFLD to identify common mechanisms. Methods and Results We performed a retrospective, single-center study of 89 adult patients with biopsy-proven NAFLD who had transthoracic echocardiography performed for any indication. Metabolomic analysis was performed on serum using ultrahigh performance liquid and gas chromatography/tandem mass spectrometry. HFpEF was defined as ejection fraction >50% plus at least 1 echocardiographic feature of HFpEF (diastolic dysfunction, abnormal left atrial size) and at least 1 heart failure sign or symptom. We performed generalized linear models to evaluate associations between individual metabolites, NAFLD, and HFpEF. Thirty-seven out of 89 (41.6%) patients met criteria for HFpEF. A total of 1151 metabolites were detected; 656 were analyzed after exclusion of unnamed metabolites and those with >30% missing values. Fifty-three metabolites were associated with the presence of HFpEF with unadjusted P value <0.05; none met statistical significance after adjustment for multiple comparisons. The majority (39/53, 73.6%) were lipid metabolites, and levels were generally increased. Two cysteine metabolites (cysteine s-sulfate and s-methylcysteine) were present at significantly lower levels in patients with HFpEF. Conclusions We identified serum metabolites associated with HFpEF in patients with biopsy-proven NAFLD, with increased levels of multiple lipid metabolites. Lipid metabolism could be an important pathway linking HFpEF to NAFLD.
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Affiliation(s)
- Kara Wegermann
- Division of Gastroenterology, Department of Medicine Duke University Health System Durham NC
| | - Marat Fudim
- Division of Cardiology, Department of Medicine Duke University Health System Durham NC
| | - Ricardo Henao
- Department of Biostatistics and Bioinformatics Duke University Durham NC
| | | | - Robert McGarrah
- Division of Cardiology, Department of Medicine Duke University Health System Durham NC
| | - Cynthia Guy
- Department of Pathology Duke University Hospital Durham NC
| | - Manal F Abdelmalek
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic Rochester MN
| | - Anna Mae Diehl
- Division of Gastroenterology, Department of Medicine Duke University Health System Durham NC
| | - Cynthia A Moylan
- Division of Gastroenterology, Department of Medicine Duke University Health System Durham NC
- Department of Medicine, Durham Veterans Affairs Medical Center Durham NC
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17
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Patel AA, Tapper EB, Kanwal F, Woodrell CD, Hansen L, Lai JC, Rogal S, McDermott C, Rakoski M, Ufere NN. Targets and study design for symptom-focused trials aimed at patients with cirrhosis: An expert consensus. Hepatol Commun 2023; 7:e0135. [PMID: 37267219 PMCID: PMC10241502 DOI: 10.1097/hc9.0000000000000135] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 03/07/2023] [Indexed: 06/04/2023] Open
Abstract
BACKGROUND Symptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures. METHODS A writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in future clinical trials, including for patients with cirrhosis. RESULTS The panel reached a consensus on key reporting features for clinical trials, along with considerations for study design. Nine key symptom targets (muscle cramps, pruritus, pain, fatigue, sexual dysfunction, sleep disorders, depression and anxiety, nausea/vomiting, and dyspnea/breathlessness) were identified. The panel selected instruments that can be considered for clinical trials based on psychometric validation and previous experience. The panel identified ongoing needs, including instrument validation, safety data, evidence about non-pharmacologic interventions, and comparative effectiveness studies. CONCLUSION This expert panel identified key design, reporting, and measurement elements to standardize processes and measures in future symptom-focused clinical trials in the context of cirrhosis.
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Affiliation(s)
- Arpan A. Patel
- Tamar and Vatche Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California, USA
- VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
| | - Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Fasiha Kanwal
- Baylor College of Medicine and Michael E DeBakey VA Medical Center, Houston, Texas, USA
| | - Christopher D. Woodrell
- Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Geriatric Research, Education and Clinical Center, James J. Peters VA Medical Center, Bronx, New York, USA
| | - Lissi Hansen
- Oregon Health & Science University, School of Nursing, Portland, Oregon, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, University of California, San Francisco, California, USA
| | - Shari Rogal
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Cara McDermott
- Division of Geriatrics, Department of Medicine, Duke University, Durham, New Carolina, USA
- Geriatric Research, Education and Clinical Center, Durham VA Medical Center, Durham, New Carolina, USA
| | - Mina Rakoski
- Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, California, USA
| | - Nneka N. Ufere
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachussetts, USA
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18
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Sheptulina AF, Yafarova AA, Golubeva JA, Mamutova EM, Kiselev AR, Drapkina OM. Clinically Meaningful Fatigue and Depression Are Associated with Sarcopenia in Patients with Non-Alcoholic Fatty Liver Disease. J Pers Med 2023; 13:932. [PMID: 37373921 DOI: 10.3390/jpm13060932] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/28/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Sarcopenia is thought to be related to an increased risk of non-alcoholic steatohepatitis and advanced liver fibrosis. Our cross-sectional single-center study was designed to analyze the prevalence of sarcopenia in patients with NAFLD and possible influencing factors. METHODS A survey on the presence of sarcopenia, fatigue, anxiety, and depression, along with a quality-of-life (QoL) assessment, was forwarded by email to 189 outpatients. Demographics, anthropometric and clinical data (laboratory test results and abdomen complete ultrasound protocol), performed within 2-4 weeks prior to the enrollment, were obtained. RESULTS Sarcopenia (defined as SARC-F score ≥ 4) was identified in 17 (15.7%) patients, all of them (100%) females, with median age (interquartile range) 56 (51-64) years. These patients had a poorer metabolic state (greater values of waist and hip circumferences, body mass index, and HOMA-IR) and significantly poorer QoL, specifically, regarding the physical component of health, compared with NAFLD patients without sarcopenia. Multivariate analysis showed that depression (OR = 1.25, 95% CI: 1.02-1.53, p = 0.035) and clinically meaningful fatigue (OR = 1.14, 95% CI: 1.04-1.26, p = 0.008) were the factors independently associated with sarcopenia in patients with NAFLD. CONCLUSION Sarcopenia is associated with depression and fatigue rather than with the severity of liver disease alone and may negatively affect QoL in patients with NAFLD.
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Affiliation(s)
- Anna F Sheptulina
- National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Adel A Yafarova
- National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia
| | - Julia A Golubeva
- National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia
| | - Elvira M Mamutova
- National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia
| | - Anton R Kiselev
- National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia
| | - Oxana M Drapkina
- National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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19
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Stepanova M, Henry L, Younossi ZM. Economic Burden and Patient-Reported Outcomes of Nonalcoholic Fatty Liver Disease. Clin Liver Dis 2023; 27:483-513. [PMID: 37024220 DOI: 10.1016/j.cld.2023.01.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
In addition to adverse clinical outcomes such as liver-related morbidity and mortality, nonalcoholic fatty liver disease (NAFLD) is associated with a substantial public health and economic burden and could also potentially impair health-related quality of life and other patient-reported outcomes. The disease also affects multiple aspects of patients' quality of life which are the most pronounced in physical health-related and fatigue domains as well as work productivity, and get more severe in patients with advanced liver disease or with non-hepatic comorbidities. The economic burden of NAFLD is substantial and is increasing, with the highest costs in those with advanced disease.
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Affiliation(s)
- Maria Stepanova
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Medical Campus, Falls Church, VA, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA; Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - Linda Henry
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Medical Campus, Falls Church, VA, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA; Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - Zobair M Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Medical Campus, Falls Church, VA, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
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20
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Liu J, Gong X, Lv H, Liu S, Jiang Y, Zhu G, Ma X, Wang J, Ye X, Gao Y, Li J, Chen G, Shi J. Is fatigue related to the severity of liver inflammation in patients with chronic liver disease? A cross-sectional study. BMJ Open 2023; 13:e069028. [PMID: 37080620 PMCID: PMC10124276 DOI: 10.1136/bmjopen-2022-069028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/22/2023] Open
Abstract
OBJECTIVES Fatigue is common in patients with chronic liver disease; however, its pathogenesis is unclear. This study aimed to provide insights into the pathogenesis of chronic liver disease-related fatigue by assessing the relationship between fatigue and the degree of inflammation in chronic liver disease. DESIGN We performed a cross-sectional study of 1374 patients with pathologically proven chronic liver disease diagnosed at the Affiliated Hospital of Hangzhou Normal University in Hangzhou, China. SETTING Primary single-centre study. PARTICIPANTS One thousand three hundred and seventy-four patients with liver biopsy-proven chronic liver disease. INTERVENTIONS The patients were divided into fatigue and non-fatigue groups according to the Chronic Liver Disease Questionnaire. Propensity score matching was used to match the baseline features of the patients in the two groups. PRIMARY AND SECONDARY OUTCOME MEASURES Liver steatosis, ballooning, inflammation and fibrosis were measured according to the pathological results of liver biopsy. Fatigue was measured using the Chronic Liver Disease Questionnaire. RESULTS Of the 1374 patients, 262 (19.67%) experienced fatigue. There were 242 and 484 patients with and without fatigue, respectively, who were successfully matched for sex, age and classification of chronic liver disease by propensity score matching. After matching, the fatigue group showed higher liver enzyme levels, inflammation grades and fibrosis stages than the non-fatigue group (p<0.05). Multivariate analysis showed that age (OR: 2.026; p=0.003), autoimmune liver disease (OR: 2.749; p=0.002) and active inflammation (OR: 1.587; p=0.003) were independent risk factors for fatigue after adjusting for confounders. The OR of the risk for fatigue increased in a stepwise manner with increasing inflammation grade in young-aged and middle-aged patients (p<0.05). This tendency was not observed in elderly patients (p>0.05). CONCLUSION Patients with chronic liver disease were burdened by fatigue, which increased progressively with rising liver inflammation severity in young-aged and middle-aged rather than elderly patients.
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Affiliation(s)
- Jing Liu
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Xiying Gong
- Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Haifeng Lv
- Department of Intensive Care Unit, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Shiyi Liu
- Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Yanming Jiang
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Geli Zhu
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Xiaojie Ma
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Jie Wang
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Xiaoping Ye
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Yidan Gao
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Jie Li
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Gongying Chen
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Junping Shi
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Department of Translational Medicine Platform, Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, China
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Yilmaz Y, Toraman AE, Alp C, Doğan Z, Keklikkiran C, Stepanova M, Younossi Z. Impairment of patient-reported outcomes among patients with non-alcoholic fatty liver disease: a registry-based study. Aliment Pharmacol Ther 2023; 57:215-223. [PMID: 36369643 DOI: 10.1111/apt.17301] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 10/20/2022] [Accepted: 10/29/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND Patients with non-alcoholic fatty liver disease (NAFLD) and more advanced fibrosis tend to have more impairment in their health-related quality of life and other patient-reported outcomes (PROs). AIM To assess the association of PROs with select non-invasive tests (NITs) for fibrosis including FAST, Agile 3+ and Agile 4 scores METHODS: We enrolled patients with an established diagnosis of NAFLD who were seen in a tertiary care clinic into the NAFLD/NASH Registry. The FAST, Agile 3+ and Agile 4 scores were calculated using liver stiffness measurements by transient elastography and laboratory parameters. PROs were assessed using FACIT-F, CLDQ-NASH and WPAI instruments (total of 17 domain and summary scores). RESULTS There were 1509 patients with NAFLD (mean age: 49 ± 11 years, 50% men, 41% employed, 30% advanced fibrosis and 20% cirrhosis). The mean FAST, Agile 3+ and Agile 4 scores were 0.39 ± 0.26, 0.35 ± 0.31 and 0.12 ± 0.23, respectively. Subjects with lower FAST, Agile 3+ and Agile 4 scores had the highest scores in select domains of FACIT-F, CLDQ-NASH and WPAI (p < 0.05 in comparison to subjects with elevated or high-risk NIT scores). Correlations with continuous NITs were significantly negative for Emotional and Functional well-being (FACIT-F), Activity/energy, Systemic symptoms, Worry and total scores (CLDQ-NASH), and Activity of WPAI (p < 0.05); the strongest was for Worry (CLDQ-NASH) with FAST (R = -0.17, p < 0.0001). The PRO scores of patients with NAFLD were lower than those of matched patients with chronic hepatitis B (p < 0.05 for 9/17 domain and summary scores). CONCLUSION Patients with NAFLD and high FAST, Agile 3+ or Agile 4 scores experience impairment of health-related quality of life.
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Affiliation(s)
- Yusuf Yilmaz
- Institute of Gastroenterology, Marmara University, İstanbul, Turkey
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
- The Global NASH Council, Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | | | - Ceyda Alp
- School of Medicine, Marmara University, İstanbul, Turkey
| | - Zehra Doğan
- School of Medicine, Marmara University, İstanbul, Turkey
| | | | - Maria Stepanova
- The Global NASH Council, Center for Outcomes Research in Liver Diseases, Washington, DC, USA
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia, USA
- Inova Medicine Service Line, Inova Health System, Falls Church, Virginia, USA
| | - Zobair Younossi
- The Global NASH Council, Center for Outcomes Research in Liver Diseases, Washington, DC, USA
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia, USA
- Inova Medicine Service Line, Inova Health System, Falls Church, Virginia, USA
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22
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Shea S, Lionis C, Atkinson L, Kite C, Lagojda L, Chaggar SS, Kyrou I, Randeva HS. Support Needs and Coping Strategies in Non-Alcoholic Fatty Liver Disease (NAFLD): A Multidisciplinary Approach to Potential Unmet Challenges beyond Pharmacological Treatment. LIVERS 2022; 3:1-20. [DOI: 10.3390/livers3010001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most frequently occurring chronic liver disease, affecting approximately 25–30% of the adult general population worldwide. NAFLD reflects excess hepatic accumulation of fat in the absence of increased alcohol intake, and, due to its close association with obesity, is frequently referred to as the ‘hepatic manifestation’ of metabolic syndrome. Indeed, a high percentage of individuals with NAFLD present with a combination of the cardio-metabolic comorbidities that are associated with the metabolic syndrome. In addition to its well-established link with the metabolic syndrome and increased risk for cardiovascular disease, NAFLD has also been associated with certain mental health issues (e.g., depression and stress). Although this link is now being increasingly recognized, there are still unmet needs regarding the holistic management of patients with NAFLD, which could further contribute to feelings of social isolation and loneliness. The latter conditions are also increasingly reported to pose a substantial risk to overall health and quality of life. To date, there is limited research that has explored these issues among patients with NAFLD, despite existing data which indicate that perceived loneliness and isolation may pose an additional health risk. Notably, many features associated with NAFLD have been related to these concepts, such as perceived stigma, fatigue, stress, and confusion regarding this diagnosis. As such, this review aimed to assess such potential problems faced by patients with NAFLD, and to explore the possibility of unmet support needs which could lead to perceived social isolation. Moreover, the importance of a compassionate approach towards such patients is discussed, together with potential coping strategies. Future research directions and the need for a multidisciplinary approach are also highlighted.
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Affiliation(s)
- Sue Shea
- Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
| | - Christos Lionis
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece
| | - Lou Atkinson
- Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Chris Kite
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- School of Public Health Studies, Faculty of Education, Health and Wellbeing, University of Wolverhampton, Wolverhampton WV1 1LY, UK
- Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry CV1 5FB, UK
| | - Lukasz Lagojda
- Clinical Evidence Based Information Service (CEBIS), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
| | | | - Ioannis Kyrou
- Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry CV1 5FB, UK
- Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK
- Laboratory of Dietetics & Quality of Life, Department of Food Science & Human Nutrition, School of Food & Nutritional Sciences, Agricultural University of Athens, 11855 Athens, Greece
| | - Harpal S. Randeva
- Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
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Younossi ZM, Paik JM, Golabi P, Younossi Y, Henry L, Nader F. The impact of fatigue on mortality of patients with non-alcoholic fatty liver disease: Data from National Health and nutrition examination survey 2005-2010 and 2017-2018. Liver Int 2022; 42:2646-2661. [PMID: 36161464 DOI: 10.1111/liv.15437] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 08/31/2022] [Accepted: 09/23/2022] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Fatigue among patients with NAFLD may negatively impact their health-related quality of life and clinical outcomes (mortality). We determined fatigue prevalence and its association with all-cause mortality among patients with NAFLD. DESIGN NHANES 2005-2010 and 2017-2018 data were used with linked mortality data. NAFLD was defined by fatty liver index for NHANES 2005-2010 and by transient elastography for NHANES 2017-2018. Fatigue was assessed by Patient Health Questionnaire. RESULTS NHANES 2005-2010 cohort (n = 5429, mean age 47.1 years, 49.7% male, 69.9% white), 37.6% had NAFLD. Compared to non-NAFLD controls, fatigue was more common in NAFLD (8.35% vs 6.0%, p = .002). Among NHANES 2017-2018 cohort (n = 3830, mean age 48.3 years, 48.6% male, 62.3% white), 36.9% had NAFLD. Compared to non-NAFLD controls, fatigue was more common among NAFLD (8.7% vs 6.2%). NAFLD had more sleep disturbance (34.0% vs 26.7%), cardiovascular disease (CVD) (10.7% vs. 6.3%), significant hepatic fibrosis (liver stiffness>8.0 kPa, 17.9% vs 3.5%) and advanced hepatic fibrosis (>13.1 kPa, 5.4% vs 0.9%; all p < .003). The presence of depression (OR: 11.52, 95% CI: 4.45-29.80, p < .0001), CVD (OR: 3.41, 95% CI: 1.02-11.34, p = .0462) and sleep disturbance (OR: 2.00, 95% CI: 1.00-3.98, p = .0491) was independently associated with fatigue; good sleep quality (OR: 0.58, 95% CI: 0.35-0.96, p = .0366) had an inverse association. By multivariable Cox model, NAFLD adults with fatigue experienced 2.3-fold higher mortality than NAFLD without fatigue (HR: 2.31, 95% CI: 1.37-3.89, p = .002). CONCLUSIONS Fatigue among those with NAFLD is associated with increased risk for mortality and is mainly driven by depression, sleep disturbance and CVD. These findings have important clinical implications.
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Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA.,Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia, USA.,Inova Medicine, Inova Health System, Falls Church, Virginia, USA
| | - James M Paik
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA.,Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia, USA.,Inova Medicine, Inova Health System, Falls Church, Virginia, USA
| | - Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA.,Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia, USA.,Inova Medicine, Inova Health System, Falls Church, Virginia, USA
| | - Youssef Younossi
- Center for Outcomes Research in Liver Diseases, Washington, District of Columbia, USA
| | - Linda Henry
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA.,Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia, USA.,Inova Medicine, Inova Health System, Falls Church, Virginia, USA.,Center for Outcomes Research in Liver Diseases, Washington, District of Columbia, USA
| | - Fatema Nader
- Center for Outcomes Research in Liver Diseases, Washington, District of Columbia, USA
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24
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Association between polypharmacy, patient-reported symptoms, and quality of life among nonalcoholic fatty liver disease patients in the United States. DRUGS & THERAPY PERSPECTIVES 2022. [DOI: 10.1007/s40267-022-00957-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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25
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Henry L, Paik J, Younossi ZM. Review article: the epidemiologic burden of non-alcoholic fatty liver disease across the world. Aliment Pharmacol Ther 2022; 56:942-956. [PMID: 35880713 DOI: 10.1111/apt.17158] [Citation(s) in RCA: 121] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/06/2022] [Accepted: 07/13/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in parallel with obesity and type 2 diabetes. AIM To review the global epidemiology of NAFLD METHODS: We retrieved articles from PubMed using search terms of NAFLD, epidemiology, prevalence, incidence, and comorbidities. RESULTS Over 250 articles were reviewed. In 2016, the global NAFLD prevalence was 25%; this increased to >30% in 2019. Prevalence in Asia, Latin America and Middle East-North Africa (MENA) was 30.8%, 34.5% and 42.6%, respectively. Prevalence increased with age. Although prevalence was higher in men, prevalence in post-menopausal women was similar. NAFLD prevalence was higher in certain subpopulations, especially among the obese and those with metabolic syndrome (MS). However, the prevalence of lean NAFLD was 11.2%. The global prevalence of non-alcoholic steatohepatitis (NASH) is estimated between 2% and 6% in the general population. Approximately 7% of patients with NAFLD have advanced fibrosis; rates were between 21% and 50% among patients with NASH. Overall mortality related to NAFLD was 15-20 per 1000 person-years, and increased substantially in patients with NASH, especially in those with components of MS. Recent data suggest mortality/morbidity from NAFLD is increasing globally but NAFLD awareness remains low among patients and healthcare providers. CONCLUSIONS NAFLD poses a global public health problem with a very high disease burden in Asia, MENA and Latin America. Research is needed to better quantify the full impact of NAFLD and to develop strategies to improve awareness and risk stratification.
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Affiliation(s)
- Linda Henry
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia, USA
| | - James Paik
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
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26
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Younossi ZM, Stepanova M, Nader F, Loomba R, Anstee QM, Ratziu V, Harrison S, Sanyal AJ, Schattenberg JM, Barritt AS, Noureddin M, Bonacci M, Cawkwell G, Wong B, Rinella M. Obeticholic Acid Impact on Quality of Life in Patients With Nonalcoholic Steatohepatitis: REGENERATE 18-Month Interim Analysis. Clin Gastroenterol Hepatol 2022; 20:2050-2058.e12. [PMID: 34274514 DOI: 10.1016/j.cgh.2021.07.020] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 07/07/2021] [Accepted: 07/12/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Nonalcoholic steatohepatitis (NASH) affects patients' health-related quality of life (HRQoL). Patient-reported outcomes (PROs) evaluating HRQoL were assessed in the RandomizEd Global Phase 3 Study to Evaluate the Impact on NASH with FibRosis of Obeticholic Acid TreatmEnt (REGENERATE) study, which showed that obeticholic acid (OCA) significantly improved fibrosis in patients with NASH. METHODS Noncirrhotic NASH patients in a phase 3, double-blind, randomized, placebo-controlled, multicenter, international study of OCA were enrolled. The Chronic Liver Disease Questionnaire-NASH and EuroQol EQ-5D-5L were administered at baseline, 6, 12, and 18 months. RESULTS There were 1218 patients (age, 54.1 ± 11.5 y; 57% women; 43% stage F3) in the expanded intent-to-treat population (stages, F1-F3) assigned randomly to 10 mg (N = 407) or 25 mg (N = 404) OCA or placebo (N = 407). Baseline measurements were balanced across treatment groups for EuroQol EQ-5D-5L and Chronic Liver Disease Questionnaire-NASH, including Itch score: 5.75 ± 1.53 (scale 1-7, with 7 representing no itching). Nineteen (1.6%) patients discontinued therapy (protocol mandated) because of grade 3 pruritus. Patients receiving 25 mg OCA experienced mild worsening of itch scores primarily in the first months of treatment: mean ± SE change from baseline -0.66 ± 0.12, -0.44 ± 0.12, and -0.42 ± 0.13 at 6, 12, and 18 months, respectively (all P < .01). No other PRO worsening was associated with 25 mg OCA. Patients experiencing fibrosis improvement, Nonalcoholic Fatty Liver Disease Activity Score decrease (by ≥2 points), or NASH resolution had greater PRO improvements in some domains. CONCLUSIONS NASH patients evaluated in REGENERATE had impaired quality of life and underlying pruritus at baseline. Improvement of NASH corresponded with improvement in several HRQoL domains. Generally mild pruritus occurs early after OCA therapy initiation and does not worsen over time. CLINICALTRIALS gov: NCT02548351.
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Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Center for Liver Diseases, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia.
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | - Fatema Nader
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | - Rohit Loomba
- University of California, San Diego, San Diego, California
| | - Quentin M Anstee
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Newcastle National Institute for Health Research Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
| | - Vlad Ratziu
- Sorbonne Université, Institute of Cardiometabolism and Nutrition, Hôpital Pitié-Salpêtrière, INSERM UMRS 1138 CRC, Paris, France
| | | | - Arun J Sanyal
- Virginia Commonwealth University, Richmond, Virginia
| | | | - A Sidney Barritt
- University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | | | | | | | - Bruce Wong
- Intercept Pharmaceuticals, New York, New York
| | - Mary Rinella
- Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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27
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Trivedi HD, Niezen S, Jiang ZG, Tapper EB. Severe Hepatic Steatosis by Controlled Attenuation Parameter Predicts Quality of Life Independent of Fibrosis. Dig Dis Sci 2022; 67:4215-4222. [PMID: 34417922 PMCID: PMC10697075 DOI: 10.1007/s10620-021-07228-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 08/12/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIM Liver fibrosis is associated with poor patient-reported outcomes (PROs), but the impact of steatosis is unknown. We aimed to evaluate the impact of steatosis on PROs independent of liver fibrosis. METHODS We evaluated the impact of steatosis, measured by Controlled-Attenuation Parameter (CAP) on transient elastography, and PROs using the 2017-2018 National Health and Nutrition Examination Survey (NHANES) database. We used univariate and multivariate logistic and ordinal regression to evaluate categorical CAP score with PROs measuring physical disability, general health and depression. RESULTS Of 4,509 participants included, 38% had severe steatosis (> 280 dB/m). Those with severe steatosis were older and more likely to be male (56% vs. 43% and 51%). On univariate analysis, severe steatosis was associated with more difficulty walking (P = 0.01), dressing (P = 0.005), lifting objects (P = 0.02), bending (P < 0.001), and moving large objects (P = 0.0006). After multivariate adjustment, severe steatosis remained associated with difficulty lifting objects (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.2-2.4, P = 0.01) and difficulty bending (OR: 1.8, 95% CI: 1.2-2.7, P = 0.006). Severe steatosis increased risk of having any of the disabilities (OR: 1.7, 95% CI: 1.2-2.4, P = 0.008) and had higher ordinal disability index (OR: 1.6, 95% CI: 1.2-2.2, P = 0.007). Lastly, severe steatosis was also associated with worse self-perceived health status (OR: 1.5, 95% CI: 1.2-1.9, P = 0.002), while general health compared to one year ago and depression trended toward significance. CONCLUSION Patients with severe steatosis are at increased risk of physical disability and have worse self-perceived health status independent of liver fibrosis.
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Affiliation(s)
- Hirsh D Trivedi
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 8E, Boston, MA, 02116, USA.
| | - Sebastian Niezen
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 8E, Boston, MA, 02116, USA
| | - Z Gordon Jiang
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 8E, Boston, MA, 02116, USA
| | - Elliot B Tapper
- Division of Gastroenterology & Hepatology, University of Michigan, Ann Arbor, MI, USA
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28
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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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29
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Li W, Kadler BK, Brindley JH, Hood G, Devalia K, Loy J, Syn WK, Alazawi W. The contribution of daytime sleepiness to impaired quality of life in NAFLD in an ethnically diverse population. Sci Rep 2022; 12:5123. [PMID: 35332193 PMCID: PMC8948283 DOI: 10.1038/s41598-022-08358-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 02/18/2022] [Indexed: 11/09/2022] Open
Abstract
Health-related quality of life (HRQoL) is lower in people with NAFLD compared to the general population. Sleep disturbance resulting in daytime sleepiness is common in patients with NAFLD, but the effect of daytime sleepiness on HRQoL in NAFLD is unclear. The prevalence and natural history of NAFLD vary in different ethnic groups, but there has been limited ethnic diversity in HrQoL studies to date. We aimed to assess whether daytime sleepiness is independently associated with reduced HRQoL in an ethnically diverse UK population. We conducted HRQoL assessments using SF-36 version 2 and Epworth Sleepiness Scale (ESS) questionnaires in 192 people with NAFLD. Multivariate linear regression was used to identify factors independently affecting HRQoL scales. People with NAFLD reported significantly reduced physical health-related SF-36 scores compared to the general UK population. South Asian NAFLD patients reported impairment in physical health, but not mental health, approximately a decade before White NAFLD patients. In multivariate linear regression, daytime sleepiness (ESS score > 10), was the most significant independent predictor of reduced physical health. Age, BMI and liver stiffness score were also significantly associated. HRQoL is impaired earlier in patients of South Asian ethnicity. ESS score > 10, indicative of excessive daytime sleepiness, is an independent predictor of reduced HRQoL in people with NAFLD regardless of ethnicity. Daytime sleepiness should be considered as a contributing factor to reduced HRQoL in clinical practice and when evaluating patient-related outcomes in clinical trials.
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Affiliation(s)
- Wenhao Li
- Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK.,Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Missouri, USA
| | - Benjamin Karl Kadler
- Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK.,Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Missouri, USA
| | - James Hallimond Brindley
- Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK.,Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Missouri, USA
| | - Gillian Hood
- Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK.,Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Missouri, USA
| | - Kalpana Devalia
- Bariatric Surgery Department, Homerton University Hospital, London, UK.,Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Missouri, USA
| | - John Loy
- Bariatric Surgery Department, Homerton University Hospital, London, UK.,Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Missouri, USA
| | - Wing-Kin Syn
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC, USA.,Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, Universidad del Pa S Vasco/Euskal Herriko Univertsitatea (UPV/EHU), Leioa, Spain.,Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Missouri, USA
| | - William Alazawi
- Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK. .,Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Missouri, USA.
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Garbuzenko DV, Belov DV. Non-alcoholic fatty liver disease as an independent factor of cardiometabolic risk of cardiovascular diseases. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:22-34. [DOI: 10.31146/1682-8658-ecg-194-10-22-34] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a pressing public health problem affecting up to a third of the world's adult population. The main reasons for its high mortality rate are cardiovascular diseases. They are caused by subclinical atherosclerosis characteristic of NAFLD, venous thromboembolic complications, functional and structural myocardial disorders, calcification of heart valves, heart rhythm and conduction disturbances. At the same time, NAFLD can serve as an independent factor of the cardiometabolic risk of their development, which is associated with atherogenic dyslipidemia, as well as the release of numerous pro-inflammatory mediators both from the pathologically altered liver and as a result of systemic endotoxemia, which is the result of disturbance of the intestinal microbiota, accompanied by a decrease in intestinal microbial gene richness., a change in its composition and function, followed by bacterial translocation. Considering that most patients with NAFLD die from cardiovascular complications, it becomes obvious that exclusively “liver-oriented” principles of their treatment cannot be sufficient, but require a multidisciplinary team approach involving cardiologists, cardiac surgeons and doctors of other related specialties.
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Obesity-Related Metabolic Dysfunction in Dairy Cows and Horses: Comparison to Human Metabolic Syndrome. Life (Basel) 2021; 11:life11121406. [PMID: 34947937 PMCID: PMC8705694 DOI: 10.3390/life11121406] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 12/06/2021] [Accepted: 12/13/2021] [Indexed: 12/17/2022] Open
Abstract
Obesity has become a serious health problem with frequent occurrence both in human and animal populations. It is estimated that it may affect over 85% of the human population and 70–80% of horses and cows by 2030. Fat cow syndrome (FCS) is a combination of metabolic, digestive, infectious, and reproductive disorders that affects obese periparturient dairy cows, and occurs most frequently in loose-housing systems, where periparturient and dry cows are fed and managed in one group disregarding the lactation stages. Equine metabolic syndrome (EMS) was named after human metabolic syndrome (MetS) and has insulin dysregulation as a central and consistent feature. It is often associated with obesity, although EMS may occur in a lean phenotype as well. Other inconsistent features of EMS are cardiovascular changes and adipose dysregulation. Laminitis is the main clinical consequence of EMS. MetS holds a 30-years old lead in research and represents a clustering of risk factors that comprise abdominal obesity, dyslipidemia, hypertension, and hyperglycemia (impaired fasting glucose or type 2 diabetes mellitus—T2DM), which are associated with doubled atherosclerotic cardiovascular disease risk, and a 5-fold increased risk for T2DM. The main aim of this review is to provide critical information for better understanding of the underlying mechanisms of obesity-related metabolic dysfunction in animals, especially in cows and horses, in comparison with MetS. Human medicine studies can offer suitable candidate mechanisms to fill the existing gap in the literature, which might be indispensable for owners to tackle FCS, EMS, and their consequences.
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Radun R, Trauner M. Role of FXR in Bile Acid and Metabolic Homeostasis in NASH: Pathogenetic Concepts and Therapeutic Opportunities. Semin Liver Dis 2021; 41:461-475. [PMID: 34289507 PMCID: PMC8492195 DOI: 10.1055/s-0041-1731707] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, increasingly contributing to the burden of liver transplantation. In search for effective treatments, novel strategies addressing metabolic dysregulation, inflammation, and fibrosis are continuously emerging. Disturbed bile acid (BA) homeostasis and microcholestasis via hepatocellular retention of potentially toxic BAs may be an underappreciated factor in the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) as its progressive variant. In addition to their detergent properties, BAs act as signaling molecules regulating cellular homeostasis through interaction with BA receptors such as the Farnesoid X receptor (FXR). Apart from being a key regulator of BA metabolism and enterohepatic circulation, FXR regulates metabolic homeostasis and has immune-modulatory effects, making it an attractive therapeutic target in NAFLD/NASH. In this review, the molecular basis and therapeutic potential of targeting FXR with a specific focus on restoring BA and metabolic homeostasis in NASH is summarized.
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Affiliation(s)
- Richard Radun
- Department of Internal Medicine III, Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria
| | - Michael Trauner
- Department of Internal Medicine III, Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria
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Glass O, Liu D, Bechard E, Guy CD, Pendergast J, Mae Diehl A, Abdelmalek MF. Perceptions of Exercise and Its Challenges in Patients With Nonalcoholic Fatty Liver Disease: A Survey-Based Study. Hepatol Commun 2021; 6:334-344. [PMID: 34697917 PMCID: PMC8793987 DOI: 10.1002/hep4.1808] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 07/13/2021] [Accepted: 08/01/2021] [Indexed: 11/13/2022] Open
Abstract
Exercise is a foundational treatment for nonalcoholic fatty liver disease (NAFLD); however, the majority of patients are unable to initiate and maintain effective exercise habits and remain at increased risk for progressive liver disease. Barriers and limitations to exercise in patients with NAFLD have not been fully identified. We performed a single survey of 94 patients with biopsy‐proven NAFLD to understand baseline physical activity and sedentary behavior, self‐perceived fitness, limitations to exercise, potential solutions to increase physical activity behavior, and perception of exercise as a foundational treatment for NAFLD. For exploratory analyses, we evaluated differences in responses to the survey by grouping severity of hepatic fibrosis as follows: nonalcoholic fatty liver (NAFL); early stage (nonalcoholic steatohepatitis [NASH] F0, NASH F1, NASH F2); and late stage (NASH F3, NASH F4). Zero weekly total physical activity was reported by 29% of patients with NAFLD. Late‐stage NASH had significantly lower vigorous (P = 0.024), walking (P = 0.029), total weekly activity (P = 0.043), and current fitness level (P = 0.022) compared to early stage NASH. Overall, 72% of patients with NAFLD reported limitations to exercise, with the greatest proportion citing lack of energy (62%), fatigue (61%), prior/current Injury (50%), and shortness of breath (49%). A preference for personal training to increase their physical activity was indicated by 66% of patients with NAFLD, and 63% preferred exercise over medication to treat NAFLD. Conclusion: The majority of patients with NAFLD have limitations to exercise but prefer exercise as a treatment option for NAFLD in the form of personal training. Patients with NAFLD may have unique physiologic limitations to exercise that worsen with fibrosis severity. Exercise interventions or services that are personalized and scalable may improve sustainability of exercise habits in the long term.
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Affiliation(s)
- Oliver Glass
- Division of General Internal Medicine, Duke University, Durham, NC, USA
| | - Daniel Liu
- Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA
| | | | - Cynthia D Guy
- Department of Pathology, Duke University, Durham, NC, USA
| | - Jane Pendergast
- Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA
| | - Anna Mae Diehl
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
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Kabarra K, Golabi P, Younossi ZM. Nonalcoholic steatohepatitis: global impact and clinical consequences. Endocr Connect 2021; 10:R240-R247. [PMID: 34486981 PMCID: PMC8558888 DOI: 10.1530/ec-21-0048] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 09/06/2021] [Indexed: 12/15/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases ranging from simple fatty infiltration of liver parenchyma to the potentially progressive type of NAFLD called nonalcoholic steatohepatitis (NASH). Given the obesity epidemic, NAFLD and NASH have reached alarming levels globally. Recent data suggest that more than a quarter of the world population is affected by NAFLD; however, the disease prevalence is higher in certain patient population, that is, 55% prevalence rate among patients with type 2 diabetes (T2DM). Besides T2DM, NAFLD is also closely related to other metabolic abnormalities, such as visceral obesity, hypertension, and hyperlipidemia. It has been suggested that stage of liver fibrosis is the most important factor associated with mortality among patients with NAFLD. Additionally, patients with T2DM have increased risk of adverse outcomes. In addition to these metabolic abnormalities, older age and some genetic factors could pose additional risks. Patients with NAFLD and NASH have significantly impaired health-related quality of life than the general population. There is also a growing economical impact of NAFLD and NASH on healthcare systems around the globe. Despite a number of promising regimens as treatment options, healthy lifestyle modification with diet and exercise remains at the core of management of NAFLD and NASH.
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Affiliation(s)
- Khaled Kabarra
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
- Inova Medicine, Inova Health System, Falls Church, Virginia, USA
- Correspondence should be addressed to Z M Younossi:
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35
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Chen Z, Liu J, Zhou F, Li H, Zhang XJ, She ZG, Lu Z, Cai J, Li H. Nonalcoholic Fatty Liver Disease: An Emerging Driver of Cardiac Arrhythmia. Circ Res 2021; 128:1747-1765. [PMID: 34043417 DOI: 10.1161/circresaha.121.319059] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.
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Affiliation(s)
- Ze Chen
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Department of Cardiology (Z.C., Z.L.), Zhongnan Hospital of Wuhan University, China
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Jiayi Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Feng Zhou
- Medical Science Research Center (F.Z., H.L.), Zhongnan Hospital of Wuhan University, China
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Haomiao Li
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Medical Science Research Center (F.Z., H.L.), Zhongnan Hospital of Wuhan University, China
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Xiao-Jing Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Zhi-Gang She
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Zhibing Lu
- Department of Cardiology (Z.C., Z.L.), Zhongnan Hospital of Wuhan University, China
| | - Jingjing Cai
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (J.C.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Hongliang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
- Basic Medical School (H.L.), Wuhan University, China
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36
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Lu G, Liu Z, Wang X, Wang C. Recent Advances in Panax ginseng C.A. Meyer as a Herb for Anti-Fatigue: An Effects and Mechanisms Review. Foods 2021; 10:foods10051030. [PMID: 34068545 PMCID: PMC8151278 DOI: 10.3390/foods10051030] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/28/2021] [Accepted: 05/06/2021] [Indexed: 12/16/2022] Open
Abstract
As an ancient Chinese herbal medicine, Panax ginseng C.A. Meyer (P. ginseng) has been used both as food and medicine for nutrient supplements and treatment of human diseases in China for years. Fatigue, as a complex and multi-cause symptom, harms life from all sides. Millions worldwide suffer from fatigue, mainly caused by physical labor, mental stress, and chronic diseases. Multiple medicines, especially P. ginseng, were used for many patients or sub-healthy people who suffer from fatigue as a treatment or healthcare product. This review covers the extract and major components of P. ginseng with the function of anti-fatigue and summarizes the anti-fatigue effect of P. ginseng for different types of fatigue in animal models and clinical studies. In addition, the anti-fatigue mechanism of P. ginseng associated with enhancing energy metabolism, antioxidant and anti-inflammatory activity is discussed.
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Affiliation(s)
| | | | - Xu Wang
- Correspondence: ; Tel.: +86-022-60912421
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Yamamura S, Nakano D, Hashida R, Tsutsumi T, Kawaguchi T, Okada M, Isoda H, Takahashi H, Matsuse H, Eguchi Y, Sumida Y, Nakajima A, Gerber L, Younossi ZM, Torimura T. Patient-reported outcomes in patients with non-alcoholic fatty liver disease: A narrative review of Chronic Liver Disease Questionnaire-non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. J Gastroenterol Hepatol 2021; 36:629-636. [PMID: 32627871 DOI: 10.1111/jgh.15172] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/17/2020] [Accepted: 07/01/2020] [Indexed: 12/14/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and one of the leading causes of hepatocellular carcinoma and liver transplantation. Moreover, patients with NAFLD frequently complain of non-specific symptoms including fatigue, abdominal discomfort, as well as anxiety, and NAFLD is reported to affect patient-reported outcomes (PROs). Thus, for clarifying the total burden of NAFLD, it is crucial to assess all associated outcomes, including not only clinical and economic outcomes but also PROs. PROs are thought to reflect what is happening in one's daily life and is an important way patients and health-care professionals communicate. There are various instruments for the assessment of PROs. Recently, a NAFLD/non-alcoholic steatohepatitis (NASH)-specific instrument called "Chronic Liver Disease Questionnaire (CLDQ)-NAFLD/NASH" has been developed. CLDQ-NAFLD/NASH comprises six domains: (i) abdominal symptoms, (ii) activity/energy, (iii) emotional health, (iv) fatigue, (v) systemic symptoms, and (vi) worry. CLDQ-NAFLD/NASH has demonstrated excellent internal consistency, face validity, content validity, and test-retest reliability. It has been sufficiently validated in two international phase 3 clinical trials. In this review, we summarize features of various instruments for assessing PROs by focusing on CLDQ-NAFLD/NASH. We also examine the validity of CLDQ-NAFLD/NASH in Japanese patients and alterations in CLDQ-NAFLD/NASH score in Japanese patients with significant hepatic fibrosis. Moreover, we discuss the utility of CLDQ-NAFLD/NASH in phase 3 clinical trials and in a real-world clinical setting.
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Affiliation(s)
- Sakura Yamamura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Dan Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Ryuki Hashida
- Department of Orthopedics, Kurume University School of Medicine, Kurume, Japan.,Division of Rehabilitation, Kurume University Hospital, Kurume, Japan
| | - Tsubasa Tsutsumi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Michiaki Okada
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Nabeshima, Japan
| | - Hiroshi Isoda
- Liver Center, Saga University Hospital, Nabeshima, Japan
| | - Hirokazu Takahashi
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Nabeshima, Japan
| | - Hiroo Matsuse
- Department of Orthopedics, Kurume University School of Medicine, Kurume, Japan.,Division of Rehabilitation, Kurume University Hospital, Kurume, Japan
| | - Yuichiro Eguchi
- Liver Center, Saga University Hospital, Nabeshima, Japan.,Locomedical General Institution, Medical cooperation Locomedical, Ogi, Japan
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Lynn Gerber
- Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Zobair M Younossi
- Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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38
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Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease-Current Knowledge, Mechanisms and Perspectives. J Clin Med 2021; 10:jcm10040673. [PMID: 33572481 PMCID: PMC7916374 DOI: 10.3390/jcm10040673] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/29/2021] [Accepted: 01/31/2021] [Indexed: 12/11/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.
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39
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O'Gorman P, Monaghan A, McGrath M, Naimimohasses S, Gormley J, Norris S. Determinants of Physical Activity Engagement in Patients With Nonalcoholic Fatty Liver Disease: The Need for an Individualized Approach to Lifestyle Interventions. Phys Ther 2021; 101:5940149. [PMID: 33104787 DOI: 10.1093/ptj/pzaa195] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 09/23/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Physical activity (PA) is an important non-pharmacological treatment for non-alcoholic fatty liver disease (NAFLD). This study investigated the determinants of PA engagement and awareness of the World Health Organization (WHO) PA guidelines in patients with NAFLD. METHODS Study participants were 101 patients with NAFLD (median age: 54 [IQR = 15] y; 53 men and 48 women) who completed 4 questionnaires: (1) a PA guideline awareness questionnaire; (2) a PA questionnaire assessing PA levels; and (3) 2 questionnaires assessing perceived barriers and motivators for engaging in PA. Binary logistic regression was performed to assess predictors of PA levels. RESULTS Twenty-four percent of participants correctly identified the recommended WHO weekly PA guidelines, and 39% adhered to the guidelines. Lack of willpower, time, and energy were the most frequently cited barrier domains. Scores for lack of willpower (odds ratio [OR] = 1.445, 95% CI = 1.088-1.919) and lack of resources (OR = 1.378, 95% CI = 1.003-1.893), and reporting 3 or more "significant" barrier domains (OR = 5.348, 95% CI = 1.792-15.873) were significant predictors of PA levels. Maintaining health and fitness was the most cited motivator domain and was a significant predictor (OR = 2.551, 95% CI = 1.253-5.208) of PA levels. CONCLUSIONS This study highlights the lack of awareness of the WHO PA guidelines and the key determinants of PA participation in patients with NAFLD. Determinants of PA should be identified at the individual level to create a personalized approach for PA maintenance for people with NAFLD to promote lifelong participation in PA. IMPACT This study closes a gap in the published data on the determinants of PA engagement in patients with NAFLD. LAY SUMMARY Physical inactivity is the fourth leading cause of global mortality and contributes to many chronic inflammatory diseases, including obesity, type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). People with NAFLD engage in less physical activity compared with people who are healthy, and this study provides new information that clinicians can use to help these patients increase their physical activity participation.
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Affiliation(s)
- Philip O'Gorman
- Discipline of Physiotherapy, University of Dublin, Trinity College, Dublin, Ireland
| | - Ann Monaghan
- Discipline of Physiotherapy, University of Dublin, Trinity College, Dublin, Ireland
| | - Marie McGrath
- Department of Hepatology, St James's Hospital, Dublin, Ireland
| | - Sara Naimimohasses
- Department of Hepatology, St James's Hospital, Dublin, Ireland.,Department of Clinical Medicine, University of Dublin, Trinity College, Dublin, Ireland
| | - John Gormley
- Discipline of Physiotherapy, University of Dublin, Trinity College, Dublin, Ireland
| | - Suzanne Norris
- Department of Hepatology, St James's Hospital, Dublin, Ireland.,Department of Clinical Medicine, University of Dublin, Trinity College, Dublin, Ireland
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40
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Abe K, Fujita M, Hayashi M, Takahashi A, Ohira H. The Efficacy of Levocarnitine Treatment in Relieving Fatigue in Patients with Cirrhosis but without Overt Hepatic Encephalopathy. Intern Med 2021; 60:3533-3542. [PMID: 34776465 PMCID: PMC8666222 DOI: 10.2169/internalmedicine.7175-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Objective In the present study, we prospectively examined the efficacy of levocarnitine in relieving symptoms of fatigue in patients with cirrhosis but without overt hepatic encephalopathy. Methods Twenty-one cirrhotic patients who were able to undergo fatigue symptom evaluations at our institution were enrolled. A total of 12 cirrhotic patients underwent levocarnitine treatment (1,200-1,800 mg/day), while 9 did not undergo levocarnitine treatment. As primary endpoints, we investigated whether or not levocarnitine treatment exerted any beneficial effects by assessing the symptoms of fatigue [8-item Short-Form Health Survey (SF-8) and Fisk Fatigue Severity Score (FFSS)] at baseline and three months after treatment. Furthermore, as exploratory secondary endpoints, we investigated whether or not levocarnitine treatment exerted ameliorative effects on oxidative stress by assessing the serum thioredoxin (TRX) and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Results The median age of the patients was 73 years old. Three men and 18 women were categorized by their Child-Pugh class (A and B in 14 and 7 patients, respectively). There were no significant differences in the clinical laboratory values between the two groups. The FFSS and SF-8 scores were significantly improved in the patients with cirrhosis who underwent levocarnitine treatment (p<0.01) but not in those who did not undergo levocarnitine treatment. Furthermore, three months after levocarnitine treatment, the serum carnitine concentrations were significantly increased, and the serum thioredoxin levels were decreased in the patients with cirrhosis who underwent levocarnitine treatment (p<0.05). Conclusion These results suggest that levocarnitine treatment may relieve symptoms of fatigue in cirrhotic patients by reducing oxidative stress.
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Affiliation(s)
- Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Masashi Fujita
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Manabu Hayashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Atsushi Takahashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
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41
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Raza S, Rajak S, Upadhyay A, Tewari A, Anthony Sinha R. Current treatment paradigms and emerging therapies for NAFLD/NASH. FRONT BIOSCI-LANDMRK 2021; 26:206-237. [PMID: 33049668 PMCID: PMC7116261 DOI: 10.2741/4892] [Citation(s) in RCA: 199] [Impact Index Per Article: 49.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one the fastest emerging manifestations of the metabolic syndrome worldwide. Non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, may culminate into cirrhosis and hepatocellular cancer (HCC) and is presently a leading cause of liver transplant. Although a steady progress is seen in understanding of the disease epidemiology, pathogenesis and identifying therapeutic targets, the slowest advancement is seen in the therapeutic field. Currently, there is no FDA approved therapy for this disease and appropriate therapeutic targets are urgently warranted. In this review we discuss the role of lifestyle intervention, pharmacological agents, surgical approaches, and gut microbiome, with regard to therapy for NASH. In particular, we focus the role of insulin sensitizers, thyroid hormone mimetics, antioxidants, cholesterol lowering drugs, incretins and cytokines as therapeutic targets for NASH. We highlight these targets aiming to optimize the future for NASH therapy.
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Affiliation(s)
- Sana Raza
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Sangam Rajak
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Aditya Upadhyay
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Archana Tewari
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Rohit Anthony Sinha
- Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India,
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42
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Doward LC, Balp MM, Twiss J, Slota C, Cryer D, Brass CA, Anstee QM, Sanyal AJ. Development of a Patient-Reported Outcome Measure for Non-Alcoholic Steatohepatitis (NASH-CHECK): Results of a Qualitative Study. PATIENT-PATIENT CENTERED OUTCOMES RESEARCH 2020; 14:533-543. [PMID: 33336323 PMCID: PMC8357766 DOI: 10.1007/s40271-020-00485-w] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 11/18/2020] [Indexed: 12/13/2022]
Abstract
Background Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease characterized by excessive liver fat accumulation, inflammation, cell injury, and fibrosis. It is viewed as largely asymptomatic in its earlier (non-cirrhotic) stages, and information on the patient-perceived impact of NASH is scarce. Objective This study aimed to develop a NASH-specific patient-reported outcome (PRO) measure (NASH-CHECK) for use as a trial endpoint, using methods compliant with regulatory expectations. Methods A NASH conceptual model was developed based on the literature and clinical/patient expert review. The model guided concept elicitation (CE) interviews in patients with non-cirrhotic NASH recruited via a US tertiary care center. NASH-CHECK content was generated via thematic analysis of CE data and review by clinical/patient experts. Cognitive debriefing (CD) interviews with US patients evaluated content validity. Results The literature review confirmed that NASH impacts on functioning and health-related quality of life (HRQoL). Overall, 23 CE and 20 CD interviews were conducted. Key symptoms reported in CE interviews included pain in the upper-right abdomen (n = 14), fatigue (n = 18), poor sleep quality (n = 12), impaired memory (n = 13), and reduced focus (n = 11); key HRQoL impacts included impaired physical functioning, reduced ability to conduct daily living tasks, reduced quality of relationships, low mood, anxiety, and self-consciousness. The 52-item first-draft NASH-CHECK was reduced to 31 items based on patient feedback on item relevance, acceptability, and comprehension. Conclusions The interviews revealed key symptoms and broad HRQoL impacts of NASH. As a disease-specific PRO measure assessing symptoms and HRQoL, the NASH-CHECK is relevant, comprehensive, and acceptable to patients and clinicians.
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Affiliation(s)
- Lynda C Doward
- RTI Health Solutions, The Pavilion, Towers Business Park, Wilmslow Road, Didsbury, Manchester, M20 2LS, UK.
| | | | - James Twiss
- RTI Health Solutions, The Pavilion, Towers Business Park, Wilmslow Road, Didsbury, Manchester, M20 2LS, UK
| | | | | | | | - Quentin M Anstee
- Translational and Clinical Research Institute, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, UK.,Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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43
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Funuyet-Salas J, Pérez-San-Gregorio MÁ, Martín-Rodríguez A, Romero-Gómez M. Psychological Biomarkers and Fibrosis: An Innovative Approach to Non-alcoholic Fatty Liver Disease. Front Med (Lausanne) 2020; 7:585425. [PMID: 33195340 PMCID: PMC7642831 DOI: 10.3389/fmed.2020.585425] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 09/09/2020] [Indexed: 12/16/2022] Open
Abstract
Background: It is unknown how perceived social support and the progression of liver damage influence the psychosocial profile of patients with non-alcoholic fatty liver disease (NAFLD). In the present study, we therefore investigated which biomarkers influence the quality of life, mental health, and coping strategies of NAFLD patients. Methods: Quality of life (SF-12 and CLDQ-NAFLD), mental health (HADS and BDI-II), and coping strategies (COPE-28) were evaluated by high or low perceived social support (MSPSS) and the presence of non-alcoholic steatohepatitis (NASH) and significant fibrosis in 492 biopsy-proven NAFLD patients. The results were compared with quality of life normality tables for the general Spanish population. We also determined whether liver histology and biopsychosocial variables predicted participants' quality of life. Results: Interactive effects were found in vitality (p = 0.05), activity (p = 0.005), anxiety (p = 0.04), and denial (p = 0.04), with NASH patients showing a higher-risk biopsychosocial profile when they perceived less social support. Furthermore, patients with low perceived social support showed lower quality of life, worse mental health, and more maladaptive coping than those with high perceived social support, regardless of NASH presence. Patients with significant fibrosis showed lower quality of life compared to those without or the general Spanish population. Patients with significant fibrosis also reported worse mental health and more maladaptive coping. Lastly, significant fibrosis, female sex, greater anxiety and depressive symptoms, and worse physical and mental health-related quality of life were found to be independent determinants of worse disease-specific quality of life in these patients. Conclusions: Low perceived social support, significant fibrosis, and female sex were independently associated with a higher-risk psychosocial profile in NAFLD. These findings support the role of psychological biomarkers based on quality of life, mental health, and coping strategies in the management of these patients and suggest the potential benefits of a psychological intervention.
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Affiliation(s)
- Jesús Funuyet-Salas
- Department of Personality, Assessment, and Psychological Treatment, Faculty of Psychology, University of Seville, Seville, Spain
| | - María Ángeles Pérez-San-Gregorio
- Department of Personality, Assessment, and Psychological Treatment, Faculty of Psychology, University of Seville, Seville, Spain
| | - Agustín Martín-Rodríguez
- Department of Personality, Assessment, and Psychological Treatment, Faculty of Psychology, University of Seville, Seville, Spain
| | - Manuel Romero-Gómez
- Unit for Clinical Management (UCM) Digestive Diseases and Ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain
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Price J, Escheik C, Weinstein A, Winter P, Gerber L, Younossi Z. Abnormal cardiac and metabolic measures correlate significantly with lower performance and activity in overweight chronic liver disease. J Clin Hypertens (Greenwich) 2020; 22:1915-1923. [PMID: 32941676 DOI: 10.1111/jch.13938] [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: 01/14/2020] [Revised: 05/13/2020] [Accepted: 05/18/2020] [Indexed: 11/29/2022]
Abstract
People with Hepatitis C (HCV) and non-alcoholic fatty liver disease (NAFLD) in the United States follow national trends toward a sedentary lifestyle and are increasingly at risk for hypertension. The intent of this study was to identify potential correlates of exercise tolerance in people with two types of chronic liver disease (CLD)-NAFLD and HCV. Measures included cardiac output, oxygen consumption and stroke volume, blood pressure, distance walked in 6 minutes, clinical laboratory tests, and medications influencing the autonomic nervous system, patient self-reports of activity, fatigue, and health-related quality of life (HRQL). A total of 67 patients completed the 6-minute walk test [45.1% Female, Age 51.7 ± 8.0 years, Body Mass Index 32.8 ± 5.9, 60% HCV]. At baseline, 70% had either diastolic (DBP) or systolic blood pressure outside normal range. Performance and cardiorespiratory measures correlated strongly with one another, but not with activity. Patients with abnormal DBP reported significantly lower maximum activity (MAS; r = -.254, P = .041, CI = -0.51 to -0.010; MAS 70.6 vs 82.5), significantly higher DBP post-6-minute walk test (r = .524, P = .0001, CI = 0.287-0.762) and significantly lower overall HRQL items related to physical domains (r = .273, P = .029, CI = -0.518 to -0.029). Mental-domain HRQL and depression measures did not correlate significantly with blood pressure. This study reports a significant correlation between both pre-hypertensive and hypertensive DBP, poor physical-domain self-reports, HRQL, and performance in CLD patients.
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Affiliation(s)
- Jillian Price
- Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA
| | - Carey Escheik
- Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA.,Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA
| | - Ali Weinstein
- Center for Study of Chronic Illness and Disability, George Mason University, Fairfax, VA, USA
| | - Patrice Winter
- Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA.,Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA
| | - Lynn Gerber
- Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA
| | - Zobair Younossi
- Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA.,Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA
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Decreased Physical Working Capacity in Adolescents With Nonalcoholic Fatty Liver Disease Associates With Reduced Iron Availability. Clin Gastroenterol Hepatol 2020; 18:1584-1591. [PMID: 31628998 DOI: 10.1016/j.cgh.2019.10.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 10/07/2019] [Accepted: 10/11/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is common and related to obesity and insulin resistance. Iron metabolism is impaired in obese individuals and iron deficiency has been associated with physical inactivity. We investigated whether iron bioavailability is reduced in patients with NAFLD and contributes to reduced cardiorespiratory fitness. METHODS We collected information on weight-adjusted, submaximal physical work capacity (PWC), ultrasound-determined hepatic steatosis, iron indices, and hematologic and metabolic parameters from 390 female and 458 male participants of the Raine Study-a longitudinal study of disease development in 2868 children in Western Australia. X2 and linear regression analyses were used to compare characteristics of study participants according to NAFLD status at age 17 years. RESULTS Fourteen percent of the cohort had NAFLD. PWC was significantly reduced in adolescents with NAFLD compared to adolescents without NAFLD (reduction of 0.17 W/kg, P = .0003, adjusted for sex and body mass index [BMI]). Iron bioavailability (assessed by mean corpuscular volume [MCV], mean corpuscular haemoglobin [MCH], transferrin saturation, and serum levels of iron) was inversely correlated with BMI in adolescents with NAFLD (P ≤ .01 for all, adjusted for sex) but not in adolescents without NAFLD (P > .30). MCV and MCH correlated with PWC (MCV, P = .002 for female and P = .0003 male participants; MCH, P = .004 for female and P = .01 for male participants), irrespective of NAFLD status. Reduced PWC was associated with lower transferrin saturation in adolescents with NAFLD (reduction of 0.012 W/kg per unit decrease in transferrin saturation, P = .007) but not in adolescents without NAFLD (reduction of 0.001 W/kg, P = .40), adjusted for sex. This association was independent of MCV or MCH. CONCLUSIONS In a well-defined cohort of adolescents, we found NAFLD to be associated with decreased cardiorespiratory fitness, independent of BMI. The relationship between transferrin saturation and PWC in adolescents with NAFLD indicates that functional iron deficiency might contribute to reductions in cardiorespiratory fitness.
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McSweeney L, Breckons M, Fattakhova G, Oluboyede Y, Vale L, Ternent L, Balp MM, Doward L, Brass CA, Beyer F, Sanyal A, Anstee QM. Health-related quality of life and patient-reported outcome measures in NASH-related cirrhosis. JHEP Rep 2020; 2:100099. [PMID: 32435754 PMCID: PMC7229498 DOI: 10.1016/j.jhepr.2020.100099] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 02/04/2020] [Accepted: 02/22/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND & AIMS Non-alcoholic steatohepatitis (NASH) is known to have a negative impact on patients' health-related quality of life (HRQoL), even before progression to cirrhosis has occurred. The burden of NASH-related cirrhosis from the patient perspective remains poorly understood. Herein, we aimed to identify the burden of disease and HRQoL impairment among patients with NASH-related compensated cirrhosis. METHODS This targeted literature review sought first to identify the humanistic burden of disease from the perspective of patients with diagnosed NASH-cirrhosis and, secondly, to identify generic or disease-specific patient-reported outcome measures (PROMs) used to assess the impact of NASH-cirrhosis. Searches were conducted in bibliographical databases, grey or unpublished literature, liver disease websites, support group websites and online blogs. A quality assessment of specific PROMs was conducted. RESULTS Patients with NASH-cirrhosis are reported to suffer from lower HRQoL than patients with non-cirrhotic NASH and the general population with respect to physical health/functioning, emotional health and worry, and mental health. Thirteen PROMs were identified, of which 4 were liver-disease specific: CLDQ, CLDQ-NAFLD, LDQoL and LDSI. The most commonly used measures do not comply with current industry or regulatory standards for PROMs and/or are not validated for use in a cirrhotic NASH population. CONCLUSIONS Patients with NASH-cirrhosis have lower HRQoL and poorer physical health than patients with non-cirrhotic NASH. However, the literature lacked detail of the everyday impact on patients' lives. Currently, a number of PROMs are available to measure the impact of the disease in patients with chronic liver conditions. The lack of studies that include qualitative insights in this population mandates further exploration and research. LAY SUMMARY It is not well understood how having non-alcoholic fatty liver disease (NAFLD)-related cirrhosis affects a person's everyday wellbeing and quality of life. Some research has been done with patients who have early stages of liver disease but not people with cirrhosis. We found that patients with NAFLD-related cirrhosis tended to have poorer health than patients without cirrhosis. But there was not very much information from patients themselves and there were no tools or questionnaires just for this group of patients.
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Key Words
- CLDQ, chronic liver disease questionnaire
- COSMIN, The COnsensus-based Standards for the selection of health Measurement INstruments
- Cirrhosis
- EMA, European Medicines Agency
- FDA, United States Food and Drug Administration
- FIS, fatigue impact scale
- HRQoL, health-related quality of life
- LDQoL, liver disease quality of life questionnaire
- LDSI, liver disease symptom index
- MS, multiple sclerosis
- NAFL, non-alcoholic fatty liver
- NAFLD
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- Non-alcoholic steatohepatitis
- PHAQ, patient-reported outcome measurement information system health assessment questionnaire
- PRO, patient-reported outcome
- PROM, patient-reported outcome measure
- QoL, quality of life
- RI, researcher interpretation
- SF-36, short form health profile 36
- health-related quality of life
- liver
- patient-reported outcome measures
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Affiliation(s)
- Lorraine McSweeney
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Matthew Breckons
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Gulnar Fattakhova
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Yemi Oluboyede
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Luke Vale
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Laura Ternent
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | | | - Lynda Doward
- RTI-Health Solutions, The Pavilion, Towers Business Park, Wilmslow Road, Didsbury, Manchester, UK
| | | | - Fiona Beyer
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Arun Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, United States
| | - Quentin M. Anstee
- Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK & Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK
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Canivet CM, Perney P, Cherick F, Orlowski M, Patouraux S, Bailly-Maitre B, Tran A, Iannelli A, Gual P, Anty R. No association between binge eating disorder and severity of non-alcoholic fatty liver disease in severely obese patients. JGH OPEN 2020; 4:525-531. [PMID: 32514465 PMCID: PMC7273712 DOI: 10.1002/jgh3.12309] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 01/07/2020] [Accepted: 01/23/2020] [Indexed: 12/19/2022]
Abstract
Background and Aim The main aim of this study was to evaluate if the binge eating disorders (BEDs) related to obesity were associated with the severity of non‐alcoholic fatty liver disease (NAFLD). Methods Severely obese patients who had been referred for bariatric surgery were included in this study at the Nice University Hospital. All patients underwent a liver biopsy at the time of surgery. Between 2008 and 2015, 388 patients had an assessable Bulimia Test (BULIT) self‐questionnaire at the time of surgery. A subgroup (n = 183), between 2011 and 2015, also responded to a Beck Depression Inventory, Hospital Anxiety and Depression Scale, and a Fatigue Impact Scale autoquestionnaire. A control group of 29 healthy people matched by age and gender was included. Results Among the 388 obese patients (median age 40 years, body mass index 41.7 kg/m2, 81% women), 14 patients had a “probable diagnosis” of BED, and 47 patients had a “high risk” of developing a BED according to the BULIT. Obese patients had significantly more severe BED, depression, anxiety, and fatigue compared to controls. Steatosis, non‐alcoholic steatohepatitis, or fibrosis was not associated with BED. Similarly, the severity of NAFLD was not associated with depression, anxiety, or fatigue. Conclusions Severely obese patients had more severe BED, depression, anxiety, and fatigue than lean subjects independent of the severity of NAFLD.
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Affiliation(s)
| | - Pascal Perney
- Addiction Medicine Hospital Grau-du-Roi Nîmes France.,Paris-Saclay University, Paris-Sud University, UVSQ, CESP, U1018 Villejuif France
| | | | | | | | | | - Albert Tran
- Cote d'Azur University, Nice Hospital, INSERM, U1065, C3M Nice France
| | - Antonio Iannelli
- Cote d'Azur University, Nice Hospital, INSERM, U1065, C3M Nice France
| | | | - Rodolphe Anty
- Cote d'Azur University, Nice Hospital, INSERM, U1065, C3M Nice France
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome (MetS) and comprises one of the largest health threats of the twenty-first century. In this chapter, we review the current state of knowledge of NAFLD and underline the striking similarities with atherosclerosis. We first describe current epidemiological data showing the staggering increase of NAFLD numbers and its related clinical and economic costs. We then provide an overview of pathophysiological hepatic processes in NAFLD and highlight the systemic aspects of NAFLD that point toward metabolic crosstalk between organs as an important cause of metabolic disease. Finally, we end by highlighting the currently investigated therapeutic approaches for NAFLD, which also show strong similarities with a range of treatment options for atherosclerosis.
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Funuyet-Salas J, Martín-Rodríguez A, Conrad R, Pérez-San-Gregorio MÁ. Psychological Biomarker Profile in NAFLD/NASH with Advanced Fibrosis. NAFLD AND NASH 2020:205-223. [DOI: 10.1007/978-3-030-37173-9_12] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Health-related Quality of Life in Nonalcoholic Fatty Liver Disease Associates With Hepatic Inflammation. Clin Gastroenterol Hepatol 2019; 17:2085-2092.e1. [PMID: 30580090 DOI: 10.1016/j.cgh.2018.12.016] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 11/17/2018] [Accepted: 12/14/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Chronic liver disease has negative effects on health-related quality of life (HRQL). We analyzed data from the European non-alcoholic fatty liver disease (NAFLD) registry to assess the effects of NAFLD on HRQL. METHODS We collected data from 304 patients (mean age, 52.3 ± 12.9 years) with histologically defined NAFLD enrolled prospectively into the European NAFLD Registry in Germany, the United Kingdom, and Spain. The chronic liver disease questionnaire (CLDQ) was completed within 6 months of liver biopsy collection. RESULTS The mean CLDQ overall score was 5.0 ± 1.2, with the lowest score in the category fatigue (4.3 ± 1.6) and the highest scores for activity (5.4 ± 1.4). Women had significantly lower CLDQ scores than men (4.6 ± 1.3 vs 5.3 ± 1.1; P < .001). We found negative correlations between CLDQ scores and presence of obesity (P < .001), type 2 diabetes (P < .001), and dyslipidaemia (P < .01). There was a negative correlation between level of aspartate aminotransferase, but not alanine aminotransferase, and HRQL. Higher histological score of steatosis (1 vs 3) resulted in lower mean CLDQ score (5.3 ± 1.1 vs 4.5 ± 1.4; P < .01); higher level of lobular inflammation (0 vs 3) also resulted in lower mean CLDQ score (5.3 ± 1.2 vs 3.9 ± 1.8; P <. 001). In contrast, advanced fibrosis (F3-4) compared to early or intermediate fibrosis (F0-2) had no significant effect on mean CLDQ score (4.9 ± 1.2 vs 5.1 ± 1.3; P = .072). In multivariate analysis, patients sex, age, presence of type 2 diabetes, and inflammation were independently associated with low HRQL. CONCLUSION In an analysis of data from the European NAFLD registry, we observed a substantial burden of symptoms in patients. In addition to age, sex, and the presence of diabetes, detection of lobular inflammation in biopsies correlated with lower HRQL.
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