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Kushiro K, Hirono H, Ohkoshi S. Platelet-activating cytokines potentially associated with MASLD-induced liver injury significantly decreased following CPAP therapy: A translational study using a fatty liver mouse model. Sleep Med 2025; 130:15-24. [PMID: 40112616 DOI: 10.1016/j.sleep.2025.03.011] [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: 11/20/2024] [Revised: 02/10/2025] [Accepted: 03/11/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND AND AIM Patients with obstructive sleep apnea (OSA) and metabolic dysfunction associated steatotic liver disease (MASLD) frequently overlap due to the high prevalence of obesity. This translational study aimed to identify cytokines linking these conditions, beginning with an analysis of fatty liver in mice. Serum cytokine levels upregulated in the fatty liver mice were subsequently examined in human OSA serum samples. METHODS Mice were fed a high-fat diet to induce fatty liver. Liver proteins were analyzed using cytokine arrays. Serum samples from seventy (70) OSA patients (with 20 non-MASLD and 50 MASLD, pre- and 6-month post-continuous positive airway pressure [CPAP] therapy) were analyzed for the cytokines identified in the mouse experiment using enzyme-linked immunosorbent assays. RESULTS Four platelet-activation chemokines/cytokines (CCL5/RANTES, P-selectin, CXCL4/PF4, and CXCL5/LIX) were upregulated in mice with fatty liver. While serum levels of these factors were not significantly higher in MASLD-OSA compared to non-MASLD-OSA patients, their levels significantly decreased 6 months after the initiation of CPAP therapy, along with a reduction in mean platelet volume. CPAP compliance was significantly associated with a reduction in CCL5 levels. Additionally, a decrease in ALT levels following 6 months of CPAP therapy was significantly associated with CPAP compliance in MASLD-OSA patients. CONCLUSIONS While platelet-activation cytokines were not directly implicated in liver injury in MASLD-OSA patients, they decreased with CPAP therapy. CPAP compliance may play a key role in ALT reduction in MASLD-OSA patients independently of body weight changes. CCL5/RANTES may be indirectly associated with liver injury in MASLD-OSA, potentially induced through intermittent hypoxia.
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Affiliation(s)
- Kosuke Kushiro
- Clinical Examination, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Niigata, Japan
| | - Haruka Hirono
- Clinical Examination, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Niigata, Japan
| | - Shogo Ohkoshi
- Clinical Examination, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Niigata, Japan.
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Hasuike S, Ozono Y, Uchida K, Ogawa S, Tamura H, Uchiyama N, Hatada H, Komaki Y, Nakamura K, Iwakiri H, Sueta M, Nagata K, Toyoki Nishimura, Matsuyama M, Sawada H, Oguri T, Sato Y, Kawakami H. An autopsy case of an adult woman with Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHAD(NET)) syndrome developing nonalcoholic steatohepatitis and hepatocellular carcinoma: A case report. Medicine (Baltimore) 2024; 103:e38383. [PMID: 39259089 PMCID: PMC11142785 DOI: 10.1097/md.0000000000038383] [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: 01/22/2024] [Revised: 04/27/2024] [Accepted: 05/07/2024] [Indexed: 09/12/2024] Open
Abstract
BACKGROUND Nonalcoholic steatohepatitis (NASH) is an important etiology of hepatocellular carcinoma (HCC), and there is no established therapy for this syndrome. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD(NET)) is an extremely rare syndrome considered to be life-threatening, with death occurring around 10 years of age. We present the oldest known autopsy case of this syndrome that developed HCC. This case provided important information on not only improving the course of this syndrome, but also understanding the natural history and therapeutic modalities of NASH and HCC. METHODS The patient was diagnosed with ROHHAD(NET) syndrome in childhood, and liver cirrhosis due to NASH was diagnosed at age 17. HCC was detected at age 20, and embolization and irradiation were performed. At age 21, she died from accidental acute pancreatitis and subsequent liver failure and pulmonary hemorrhage. RESULTS Rapid onset of obesity, hypoventilation, and hypothalamic disturbance appeared in childhood and was diagnosed as this syndrome. At age 17, liver cirrhosis due to NASH was diagnosed by liver biopsy, and at age 20, HCC was diagnosed by imaging. Transarterial chemoembolization and irradiation were performed, and the HCC was well controlled for a year. CONCLUSION At age 21, she died from accidental acute pancreatitis, subsequent liver failure and pulmonary hemorrhage. Autopsy revealed that the HCC was mostly necrotized. This case was valuable not only for other ROHHAD(NET) syndrome cases, but also in improving our understanding of the natural history of NASH and HCC.
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Affiliation(s)
- Satoru Hasuike
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Yoshinori Ozono
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Keisuke Uchida
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Souichiro Ogawa
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Hotaka Tamura
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Naomi Uchiyama
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Hiroshi Hatada
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Yuri Komaki
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Kenichi Nakamura
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Hisayoshi Iwakiri
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Mitsue Sueta
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Kenji Nagata
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
| | - Toyoki Nishimura
- Faculty of Medicine, Division of Pediatrics, University of Miyazaki, Miyazaki, Japan
| | - Misayo Matsuyama
- Faculty of Medicine, Division of Pediatrics, University of Miyazaki, Miyazaki, Japan
| | - Hirotake Sawada
- Faculty of Medicine, Division of Pediatrics, University of Miyazaki, Miyazaki, Japan
| | - Toshiyuki Oguri
- Faculty of Medicine, Department of Pathology, University of Miyazaki, Miyazaki, Japan
| | - Yuichiro Sato
- Faculty of Medicine, Department of Pathology, University of Miyazaki, Miyazaki, Japan
| | - Hiroshi Kawakami
- Faculty of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan
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Gu C, Bernstein N, Mittal N, Kurnool S, Schwartz H, Loomba R, Malhotra A. Potential Therapeutic Targets in Obesity, Sleep Apnea, Diabetes, and Fatty Liver Disease. J Clin Med 2024; 13:2231. [PMID: 38673503 PMCID: PMC11050527 DOI: 10.3390/jcm13082231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 04/07/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
Obesity and metabolic syndrome affect the majority of the US population. Patients with obesity are at increased risk of developing type 2 diabetes (T2DM), obstructive sleep apnea (OSA), and metabolic dysfunction-associated steatotic liver disease (MASLD), each of which carry the risk of further complications if left untreated and lead to adverse outcomes. The rising prevalence of obesity and its comorbidities has led to increased mortality, decreased quality of life, and rising healthcare expenditures. This phenomenon has resulted in the intensive investigation of exciting therapies for obesity over the past decade, including more treatments that are still in the pipeline. In our present report, we aim to solidify the relationships among obesity, T2DM, OSA, and MASLD through a comprehensive review of current research. We also provide an overview of the surgical and pharmacologic treatment classes that target these relationships, namely bariatric surgery, the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptor agonists.
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Affiliation(s)
- Christina Gu
- Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92037, USA; (N.B.); (N.M.); (S.K.); (R.L.)
| | - Nicole Bernstein
- Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92037, USA; (N.B.); (N.M.); (S.K.); (R.L.)
| | - Nikita Mittal
- Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92037, USA; (N.B.); (N.M.); (S.K.); (R.L.)
| | - Soumya Kurnool
- Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92037, USA; (N.B.); (N.M.); (S.K.); (R.L.)
| | - Hannah Schwartz
- Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA;
| | - Rohit Loomba
- Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92037, USA; (N.B.); (N.M.); (S.K.); (R.L.)
| | - Atul Malhotra
- Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92037, USA; (N.B.); (N.M.); (S.K.); (R.L.)
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Bu LF, Xiong CY, Zhong JY, Xiong Y, Li DM, Hong FF, Yang SL. Non-alcoholic fatty liver disease and sleep disorders. World J Hepatol 2024; 16:304-315. [PMID: 38577533 PMCID: PMC10989311 DOI: 10.4254/wjh.v16.i3.304] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 01/11/2024] [Accepted: 02/18/2024] [Indexed: 03/27/2024] Open
Abstract
Studies have shown that non-alcoholic fatty liver disease (NAFLD) may be associated with sleep disorders. In order to explore the explicit relationship between the two, we systematically reviewed the effects of sleep disorders, especially obstructive sleep apnea (OSA), on the incidence of NAFLD, and analyzed the possible mechanisms after adjusting for confounding factors. NAFLD is independently associated with sleep disorders. Different sleep disorders may be the cause of the onset and aggravation of NAFLD. An excessive or insufficient sleep duration, poor sleep quality, insomnia, sleep-wake disorders, and OSA may increase the incidence of NAFLD. Despite that some research suggests a unidirectional causal link between the two, specifically, the onset of NAFLD is identified as a result of changes in sleep characteristics, and the reverse relationship does not hold true. Nevertheless, there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD. Further research is needed to establish a clear relationship between NAFLD and sleep disorders. This will lay the groundwork for earlier identification of potential patients, which is crucial for earlier monitoring, diagnosis, effective prevention, and treatment of NAFLD.
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Affiliation(s)
- Lu-Fang Bu
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Chong-Yu Xiong
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Jie-Yi Zhong
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Yan Xiong
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Dong-Ming Li
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Fen-Fang Hong
- Experimental Center of Pathogen Biology, College of Medicine, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Shu-Long Yang
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China.
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Hany M, Abouelnasr AA, Abdelkhalek MH, Ibrahim M, Aboelsoud MR, Hozien AI, Torensma B. Effects of obstructive sleep apnea on non-alcoholic fatty liver disease in patients with obesity: a systematic review. Int J Obes (Lond) 2023; 47:1200-1213. [PMID: 37696927 PMCID: PMC10663145 DOI: 10.1038/s41366-023-01378-2] [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: 03/27/2023] [Revised: 08/16/2023] [Accepted: 08/30/2023] [Indexed: 09/13/2023]
Abstract
INTRODUCTION Obesity has been linked to non-alcoholic fatty liver disease (NAFLD), a widespread chronic liver ailment, as well as obstructive sleep apnea (OSA). The development of NAFLD is influenced by repeated intermittent hypoxia, a feature of OSA. METHODS This systematic review (SR) investigated CENTRAL, PubMed, and EMBASE databases. The endpoint of this SR was to assess which OSA-related indicators could predict the presence of NAFLD and the effect of bariatric metabolic surgery (BMS) on improving OSA and NAFLD over time. RESULTS Compared to previous SRs published in 2013, 14 new publications were added to our SR, alongside studies conducted prior to 2013. The SR ultimately included 28 studies (18 cross-sectional and 10 cohort trials). In the majority of studies, significant correlations were observed between OSA, OSA-related outcomes, and NAFLD. However, the apnea-hypopnea index (AHI) alone proved to be an inadequate predictor of NAFLD. Instead, respiratory and metabolic changes were found to alleviate oxidative stress induced by hypoxemia. Six studies involved patients who underwent BMS, with one evaluating patients before and after BMS, revealing associations between increased OSA and NAFLD improvement following BMS. Six months after surgery, 100% of patients in the mild-to-moderate OSA group were free from fatty liver, and an 89% reduction was observed in the severe OSA group. CONCLUSION For the first time, BMS has been tested in treating both OSA and NAFLD pre and postoperative with positive results. Further research, ideally with histological and functional data, is needed to confirm these findings. The SR identified 14 distinct liver outcome tests; however, high heterogeneity and incomplete data precluded a meta-analysis. It is imperative to pay greater attention to the influence of OSA-related factors and uniformity in liver outcomes testing concerning NAFLD. To accomplish this, study designs should be enhanced by incorporating more comprehensive pre- and postoperative evaluations, extending follow-up periods, and employing a more consistent methodology for liver diagnosis in patients with obesity.
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Affiliation(s)
- Mohamed Hany
- Department of Surgery, Medical Research Institute, Alexandria University, Alexandria Governorate, Egypt.
- Madina Women's Hospital (IFSO certified center, European chapter), Alexandria Governorate, Egypt.
| | - Anwar Ashraf Abouelnasr
- Department of Surgery, Medical Research Institute, Alexandria University, Alexandria Governorate, Egypt
| | | | - Mohamed Ibrahim
- Department of Surgery, Medical Research Institute, Alexandria University, Alexandria Governorate, Egypt
| | - Mostafa R Aboelsoud
- Department of Surgery, Medical Research Institute, Alexandria University, Alexandria Governorate, Egypt
| | - Adel Ibrahim Hozien
- Department of Anesthesia and pain management, Medical Research Institute Alexandria University, Alexandria Governorate, Egypt
| | - Bart Torensma
- Leiden University Medical Center (LUMC), Leiden, The Netherlands
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Sircu V, Colesnic SI, Covantsev S, Corlateanu O, Sukhotko A, Popovici C, Corlateanu A. The Burden of Comorbidities in Obstructive Sleep Apnea and the Pathophysiologic Mechanisms and Effects of CPAP. Clocks Sleep 2023; 5:333-349. [PMID: 37366660 DOI: 10.3390/clockssleep5020025] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 05/22/2023] [Accepted: 06/13/2023] [Indexed: 06/28/2023] Open
Abstract
Micro-arousals and the repeated desaturation of oxyhemoglobin, which are typical in obstructive sleep apnea syndrome (OSAS), have adverse effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction), cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), and neuropsychiatric complications as well as a wide range of malignancies. These, in turn, have multilateral effects on familial, occupational, and social life, as well as increasing the risks of road traffic accidents and accidents at the workplace. Awareness, timely screening, and the prevention of complications play important roles in diagnosing and treating comorbid conditions. This review focuses on comorbidities in OSAS and the effect of Continuous Positive Airway Pressure (CPAP) therapy on their prognoses.
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Affiliation(s)
- Victoria Sircu
- Division of Pneumology and Allergology, Department of Internal Medicine, State University of Medicine and Pharmacy Nicolae Testemitanu, MD-2004 Chisinau, Moldova
| | - Silvia-Iaroslava Colesnic
- Division of Pneumology and Allergology, Department of Internal Medicine, State University of Medicine and Pharmacy Nicolae Testemitanu, MD-2004 Chisinau, Moldova
| | - Serghei Covantsev
- Department of Clinical Research and Development, Botkin Hospital, 125284 Moscow, Russia
- Department of Emergency Medicine № 76, Botkin Hospital, 125284 Moscow, Russia
| | - Olga Corlateanu
- Department of Internal Medicine, State University of Medicine and Pharmacy Nicolae Testemitanu, MD-2004 Chisinau, Moldova
| | - Anna Sukhotko
- Department of General Oncology № 71, Botkin Hospital, 125284 Moscow, Russia
| | - Cristian Popovici
- Division of Pneumology and Allergology, Department of Internal Medicine, State University of Medicine and Pharmacy Nicolae Testemitanu, MD-2004 Chisinau, Moldova
| | - Alexandru Corlateanu
- Division of Pneumology and Allergology, Department of Internal Medicine, State University of Medicine and Pharmacy Nicolae Testemitanu, MD-2004 Chisinau, Moldova
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Potential Diagnostic and Monitoring Biomarkers of Obstructive Sleep Apnea-Umbrella Review of Meta-Analyses. J Clin Med 2022; 12:jcm12010060. [PMID: 36614858 PMCID: PMC9821668 DOI: 10.3390/jcm12010060] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 12/11/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Obstructive sleep apnea (OSA) is a prevalent, underdiagnosed disease that imposes a significant impact on the health and wellbeing of patients and a financial burden on individuals, their families, and society. Development of new methods of testing other than an overnight sleep study, such as measurement of serum or plasma biomarkers, may provide an easier diagnostic process to identify patients with OSA and allow earlier initiation of treatment, which might prevent serious comorbidities. We conducted a systematic review and quality assessment of available meta-analyses regarding potential diagnostic and monitoring biomarkers of obstructive sleep apnea. A total of 14 sets of candidate biomarkers displayed differences in levels or concentrations in OSA patients compared to non-OSA controls, and decreased after OSA treatment: CRP, IL-6, TNF-α, Il-8, HCY, ICAM-1, VCAM-1, VEGF, TC, LDLc, HDLc, TG, leptin, MDA, ALT, AST, IGF-1, adiponectin, and cortisol. This review summarizes the evidence for OSA-associated potential biomarkers and demonstrates that the quality of available studies, as measured by AMSTAR2, is often low and associated with a high risk of bias.
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Sheng W, Ji G, Zhang L. Management of non-alcoholic fatty liver disease patients with sleep apnea syndrome. World J Gastroenterol 2022; 28:6099-6108. [PMID: 36483151 PMCID: PMC9724487 DOI: 10.3748/wjg.v28.i43.6099] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 10/20/2022] [Accepted: 11/06/2022] [Indexed: 11/16/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is strongly associated with sleep apnea syndrome (SAS). Many NAFLD patients have SAS, and obstructive sleep apnea hypopnea syndrome is also considered to be an independent risk factor for NAFLD, as it contributes to the progression of NAFLD via oxidative stress, lipid peroxidation, inflammation, and insulin resistance. This review aims to provide some recommendations for the management of NAFLD patients with SAS, including diet, exercise, weight loss, and continuous positive airway pressure. This review also highlights the importance of effective strategies in NAFLD prevention and treatment.
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Affiliation(s)
- Wei Sheng
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Guang Ji
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Li Zhang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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9
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Yu L, Lin C, Chen X, Teng Y, Zhou S, Liang Y. A Meta-Analysis of Sleep Disorders and Nonalcoholic Fatty Liver Disease: Potential Causality and Symptom Management. Gastroenterol Nurs 2022; 45:354-363. [PMID: 35913418 DOI: 10.1097/sga.0000000000000658] [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: 08/07/2021] [Accepted: 11/29/2021] [Indexed: 01/10/2023] Open
Abstract
Nonalcoholic fatty liver disease is a type of metabolic disease, and recent research indicates that it may be associated with sleep disorders. We conducted a meta-analysis of current studies to estimate the associations between nonalcoholic fatty liver disease and sleep situation, including sleep duration, daytime sleepiness, and sleep disorder. This study follows the checklist of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Articles in the recent 10 years were searched from five databases. Eighteen articles, which met the eligibility criteria, were included in this meta-analysis. The results show that patients with nonalcoholic fatty liver disease have a shorter sleep duration and higher Epworth Sleepiness Scale score. Patients with short sleep duration (≤6 hours per night) or with obstructive sleep apnea have a higher risk of nonalcoholic fatty liver disease. In conclusion, there is a significant association between nonalcoholic fatty liver disease and sleep disorders in the included studies. In addition, patients with nonalcoholic fatty liver disease may have more severe daytime sleepiness and shorter sleep duration. More attention should be paid to the sleep situation of nonalcoholic fatty liver disease patients to potentially slow the disease progression.
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Affiliation(s)
- Lebing Yu
- Lebing Yu, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Chenli Lin, PhD, MD, is an associate professor, School of Medicine, Jinan University, Guangzhou, China
- Xinhe Chen, is BS MED candidate, School of Stomatology, Jinan University, Guangzhou, China
- Yuxin Teng, BSN, RN, is MPH candidate, School of Nursing, Jinan University, Guangzhou, China
- Shuang Zhou, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Yinji Liang, PhD, MD, RN, is an associate professor, School of Nursing, Jinan University, Guangzhou, China
| | - Chenli Lin
- Lebing Yu, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Chenli Lin, PhD, MD, is an associate professor, School of Medicine, Jinan University, Guangzhou, China
- Xinhe Chen, is BS MED candidate, School of Stomatology, Jinan University, Guangzhou, China
- Yuxin Teng, BSN, RN, is MPH candidate, School of Nursing, Jinan University, Guangzhou, China
- Shuang Zhou, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Yinji Liang, PhD, MD, RN, is an associate professor, School of Nursing, Jinan University, Guangzhou, China
| | - Xinhe Chen
- Lebing Yu, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Chenli Lin, PhD, MD, is an associate professor, School of Medicine, Jinan University, Guangzhou, China
- Xinhe Chen, is BS MED candidate, School of Stomatology, Jinan University, Guangzhou, China
- Yuxin Teng, BSN, RN, is MPH candidate, School of Nursing, Jinan University, Guangzhou, China
- Shuang Zhou, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Yinji Liang, PhD, MD, RN, is an associate professor, School of Nursing, Jinan University, Guangzhou, China
| | - Yuxin Teng
- Lebing Yu, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Chenli Lin, PhD, MD, is an associate professor, School of Medicine, Jinan University, Guangzhou, China
- Xinhe Chen, is BS MED candidate, School of Stomatology, Jinan University, Guangzhou, China
- Yuxin Teng, BSN, RN, is MPH candidate, School of Nursing, Jinan University, Guangzhou, China
- Shuang Zhou, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Yinji Liang, PhD, MD, RN, is an associate professor, School of Nursing, Jinan University, Guangzhou, China
| | - Shuang Zhou
- Lebing Yu, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Chenli Lin, PhD, MD, is an associate professor, School of Medicine, Jinan University, Guangzhou, China
- Xinhe Chen, is BS MED candidate, School of Stomatology, Jinan University, Guangzhou, China
- Yuxin Teng, BSN, RN, is MPH candidate, School of Nursing, Jinan University, Guangzhou, China
- Shuang Zhou, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Yinji Liang, PhD, MD, RN, is an associate professor, School of Nursing, Jinan University, Guangzhou, China
| | - Yinji Liang
- Lebing Yu, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Chenli Lin, PhD, MD, is an associate professor, School of Medicine, Jinan University, Guangzhou, China
- Xinhe Chen, is BS MED candidate, School of Stomatology, Jinan University, Guangzhou, China
- Yuxin Teng, BSN, RN, is MPH candidate, School of Nursing, Jinan University, Guangzhou, China
- Shuang Zhou, BSN, RN, is MSN candidate, School of Nursing, Jinan University, Guangzhou, China
- Yinji Liang, PhD, MD, RN, is an associate professor, School of Nursing, Jinan University, Guangzhou, China
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Chi ZC. Research status and progress of metabolic associated fatty liver disease. Shijie Huaren Xiaohua Zazhi 2022; 30:1-16. [DOI: 10.11569/wcjd.v30.i1.1] [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: 02/06/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD) is a more appropriate general predicate to describe non-alcoholic fatty liver disease. The new definition lists metabolic dysfunction as an important cause of liver disease, demonstrates the high heterogeneity of this condition, and speeds up the transformation path to new treatment. The incidence of extrahepatic complications and related diseases of MAFLD far exceed that of the liver disease itself, which seriously threatens human health. In view of the current insufficient understanding of its severity, and the imperfect understanding of the disease scope, pathogenesis, and diagnosis of extrahepatic complications, especially the lack of effective drug treatment, this paper introduces and reviews the research status and progress of extrahepatic complications of MAFLD.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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11
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The Snoring Index Identifies Risk of Non-Alcoholic Fatty Liver Disease in Patients with Obstructive Sleep Apnea Syndrome. BIOLOGY 2021; 11:biology11010010. [PMID: 35053008 PMCID: PMC8772878 DOI: 10.3390/biology11010010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 12/17/2021] [Accepted: 12/20/2021] [Indexed: 12/16/2022]
Abstract
Simple Summary Obstructive sleep apnea syndrome (OSA) and non-alcoholic fatty liver disease (NAFLD) are very common and share underlying metabolic risk factors. It remains unclear how exactly the two diseases are related. In this study, patients with obstructive sleep apnea were evaluated for the presence of NAFLD with the aim of finding parameters in polysomnography that may indicate NAFLD. The snoring index turned out to be the most valuable and a very reliable screening tool for the presence of NAFLD—independent of other metabolic risk factors. Abstract Background: The aim of this observational cohort study was to explore the severity of liver disease in patients with suspected obstructive sleep apnea in Germany. Methods: Patients undergoing polysomnography or home sleep apnea testing (HSAT) as an evaluation for the presence of OSA were screened using vibration-controlled transient elastography (VCTE) and continuous attenuation parameter (CAP) with a Fibroscan ® Mini 430. Clinical and laboratory data were collected following the overnight exam. Results: In total, 78 patients (28 female (35.9%), mean age 54.2 years) with OSA defined by an apnea-hypopnea-index >5 events/hour were included between OCT 2020 and APR 2021. Patients exhibited a high metabolic risk profile with 17% known diabetes mellitus type 2 (T2D), 62% arterial hypertension, 14% hyperlipidemia and 36% BMI > 30 kg/m2. The prevalence of steatosis defined by a CAP > 280 dB/m was 54%. The prevalence of at least significant fibrosis was 16% (E > 9.0 kPa). Interestingly, patients with a snoring index above the median of 278/h showed significantly higher CAP-values (p = 0.0002). In addition, the proportion of oxygen saturations below 90% (t90) correlated with CAP-values (p = 0.02), as well as metabolic risk factors including increased waist circumference (p = 0.005) and body mass index (BMI) (p = 0.035). On the other hand, the apnea-hypopnea-index (AHI) as a marker of OSA severity did not correlate with VCTE, CAP or laboratory parameters. Conclusion: Patients with moderate to severe OSA have a high prevalence of hepatic steatosis. The snoring index is an easy-to-use clinical tool to identify patients at risk for relevant liver disease within the larger group of patients with OSA.
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12
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Anatomical Brain Changes and Cognitive Abilities in Patients with Obstructive Sleep Apnea Syndrome and Nonalcoholic Fatty Liver Disease. Can J Gastroenterol Hepatol 2021; 2021:8873652. [PMID: 34722411 PMCID: PMC8550849 DOI: 10.1155/2021/8873652] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 06/14/2021] [Accepted: 09/25/2021] [Indexed: 12/26/2022] Open
Abstract
Obstructive sleep apnea (OSA) is characterized by repetitive complete or partial collapse of the upper airway and reduction of airflow during sleep. It is associated with significantly increased daytime muscle sympathetic nerve activity thought to result from the repetitive intermittent periods of hypoxemia during sleep and brain alterations that are likely to result. Different brain regions are affected by subsequent hypoxia/anoxia. Neurodegenerative processes result in measurable atrophy of cortical gray matter in the temporal lobes and posterior cingulate cortex, as well as in subcortical structures such as the hippocampus, amygdala, and thalamus. This study involved a group of firstly diagnosed, therapy-naive, nonalcoholic fatty liver disease (NAFLD) patients, out of which 144 (96 males and 48 females), aged 34-57 (mean 47.88 ± 6.07), satisfied the recruiting criteria for the study and control groups. All the patients underwent MRI scanning, polysomnography testing, and cognitive evaluation. Cognitively, worse results were obtained in the group with OSA (p < 0.05) and NAFLD (p=0.047). A significant decrease in volumes of cortical and subcortical structures was revealed (p < 0.001). In conclusion, brain deterioration followed by cognitive impairment is, most likely, the result of intermittent hypoxia and anoxia episodes that initiate the domino process of deteriorating biochemical reactions in the brain.
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13
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Hirono H, Watanabe K, Hasegawa K, Kohno M, Terai S, Ohkoshi S. Impact of continuous positive airway pressure therapy for nonalcoholic fatty liver disease in patients with obstructive sleep apnea. World J Clin Cases 2021; 9:5112-5125. [PMID: 34307562 PMCID: PMC8283589 DOI: 10.12998/wjcc.v9.i19.5112] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/28/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Obstructive sleep apnea (OSA) has been suggested as an independent risk factor for nonalcoholic fatty liver disease (NAFLD), and continuous positive airway pressure (CPAP) is the first-line therapy for OSA.
AIM To clarify the efficacy of effective CPAP therapy on NAFLD of OSA patients by serum markers and transient elastography (TE) using FibroScan® (Echosens, Paris, France).
METHODS We prospectively enrolled 123 consecutive patients with OSA who met the indications for CPAP. Liver fibrosis and steatosis were assessed using TE. Before and after 6 mo of CPAP therapy, serum markers and TE were assessed for all patients. The mean usage rate of CPAP therapy for 6 mo was arbitrarily calculated in each patient and expressed as “mean compliance index” (m-CI).
RESULTS In 50 OSA patients with NAFLD, both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly decreased after 6 mo of CPAP therapy. Univariate analysis showed that decreased body weight (BW), decreased body mass index (BMI), decreased AST level, decreased hemoglobin A1c, and high m-CI were significantly related with improved ALT level. In multivariate regression model adjusted for quantities of BW change during 6 mo of CPAP therapy, high m-CI tended to improve ALT level (P = 0.051). All 17 OSA patients with NAFLD, high m-CI and no BMI changes showed significant improvements in AST and ALT levels. Meanwhile, no significant changes in TE data or serum fibrosis markers were seen.
CONCLUSION Some NAFLD could be associated with chronic intermittent hypoxia due to OSA independent of BW changes. In those cases, adequate reoxygenation from effective CPAP therapy may improve NAFLD.
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Affiliation(s)
- Haruka Hirono
- Department of Internal Medicine, The Nippon Dental University School of Life Dentistry at Niigata, Niigata 951-8580, Japan
| | - Kazuhiko Watanabe
- Department of Internal Medicine, The Nippon Dental University School of Life Dentistry at Niigata, Niigata 951-8580, Japan
| | - Katsuhiko Hasegawa
- Department of Internal Medicine, The Nippon Dental University School of Life Dentistry at Niigata, Niigata 951-8580, Japan
| | - Masaki Kohno
- The Center for Dental Sleep Medicine, The Nippon Dental University Niigata Hospital, Niigata 951-8580, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan
| | - Shogo Ohkoshi
- Department of Internal Medicine, The Nippon Dental University School of Life Dentistry at Niigata, Niigata 951-8580, Japan
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14
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Chen LD, Chen MX, Chen GP, Lin XJ, Huang JF, Zeng AM, Huang YP, Lin QC. Association between obstructive sleep apnea and non-alcoholic fatty liver disease in pediatric patients: a meta-analysis. Pediatr Obes 2021; 16:e12718. [PMID: 32881371 DOI: 10.1111/ijpo.12718] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 07/02/2020] [Accepted: 08/07/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Some studies have reported a relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in pediatric population. However, this issue remains controversial. OBJECTIVES The purpose of the present study was to investigate the association between OSA and NAFLD in pediatric population. METHODS We systematically searched PubMed, Web of Science, Embase for eligible studies. The data involving markers of NAFLD including alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic inflammation, hepatic fibrosis of both OSA group and control group were extracted. Pooled standardised mean difference (SMD) and weighted mean difference (WMD) were appropriately calculated through a fixed or random-effect model. RESULTS Nine cross-sectional studies with 1133 children and adolescents were included. OSA was significantly associated with ALT, AST, and NAFLD fibrosis stage, but not NAFLD inflammation grade. Subgroup analysis indicated that both mild OSA and severe OSA were significantly associated with elevated ALT and AST. Furthermore, in the studies with all main confounding factors (age, gender, and BMI) matched, OSA group had higher ALT and AST levels than control group. CONCLUSIONS This meta-analysis suggested that OSA was associated with NAFLD evidenced by elevated liver enzymes and progressive hepatic fibrosis in pediatric population. Screening and monitoring of NAFLD in pediatric patients with obesity-related OSA are necessary.
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Affiliation(s)
- Li-Da Chen
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Meng-Xue Chen
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Gong-Ping Chen
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Xue-Jun Lin
- Department of Laboratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Jie-Feng Huang
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Ai-Ming Zeng
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Ya-Ping Huang
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Qi-Chang Lin
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Provincial Sleep-disordered Breathing Clinic Center, Fuzhou, China.,Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, China
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15
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Plotogea OM, Ilie M, Bungau S, Chiotoroiu AL, Stanescu AMA, Diaconu CC. Comprehensive Overview of Sleep Disorders in Patients with Chronic Liver Disease. Brain Sci 2021; 11:brainsci11020142. [PMID: 33499194 PMCID: PMC7911845 DOI: 10.3390/brainsci11020142] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/16/2021] [Accepted: 01/19/2021] [Indexed: 12/12/2022] Open
Abstract
The impact of sleep disorders (SDs) on patients with chronic liver diseases (CLD) is tremendous. SDs are frequently encountered among these patients and interfere with their quality of life. This review aims to present the data available so far about the prevalence, phenotypes, and proposed pathophysiological mechanisms of SDs in CLD. Moreover, we proposed to search the literature regarding the most reliable methods to assess SDs and the possible therapeutic options in patients with CLD. The main results of this review show that when it comes to prevalence, the percentages reported vary widely between studies performed among populations from the USA or Europe and those coming from Asian countries. Furthermore, it has been proven that SDs may also be present in the absence of neurocognitive disorders attributable to hepatic encephalopathy (HE), which contradicts traditional suppositions where SDs were considered part of the clinical scenario of HE. Currently, there are no specific recommendations or protocols to assess SDs in CLD patients and data about the therapeutic management are limited. Taking into consideration their impact, a protocol for diagnosing and managing SDs should be developed and included in the daily practice of hepatologists.
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Affiliation(s)
- Oana-Mihaela Plotogea
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Correspondence: (O.-M.P.); (C.C.D.)
| | - Madalina Ilie
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
| | | | | | - Camelia Cristina Diaconu
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Correspondence: (O.-M.P.); (C.C.D.)
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Shah NM, Malhotra AM, Kaltsakas G. Sleep disorder in patients with chronic liver disease: a narrative review. J Thorac Dis 2020; 12:S248-S260. [PMID: 33214928 PMCID: PMC7642630 DOI: 10.21037/jtd-cus-2020-012] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Sleep disturbance is a common feature of chronic liver disease (CLD) with impact on health-related quality of life; 60-80% of patients with CLD report subjective poor sleep; frequent presentations of sleep disturbance include insomnia, reduced sleep efficiency, increased sleep latency, reduced time in rapid eye movement (REM) sleep, restless leg syndrome and excessive daytime sleepiness (EDS). Key contributors to sleep disturbance include hepatic encephalopathy (HE) and circadian rhythm imbalance due to altered melatonin metabolism. Specific conditions causing CLD, such as non-alcoholic fatty liver disease (NAFLD), chronic viral hepatitis and primary biliary cholangitis (PBC) result in different types of sleep disturbance, and the treatment of these conditions can often also lead to sleep disturbance. There are currently limited management options for sleep disturbance in CLD. Obstructive sleep apnoea (OSA) is a common condition that causes chronic intermittent hypoxia due to airway collapse during sleep. This chronic intermittent hypoxia appears to contribute to the development of NAFLD. The presence of reactive oxygen species and the overexpression of hypoxia inducible factor 1-alpha secondary to hypoxia may be responsible for the second 'hit' of the 'two-hit' hypothesis of NAFLD. Treatment of the intermittent hypoxia with continuous positive airway pressure therapy has limited efficacy against liver dysfunction. There remain many outstanding areas of investigation in the management of sleep disturbance in CLD, and of liver dysfunction in OSA.
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Affiliation(s)
- Neeraj Mukesh Shah
- Lane Fox Respiratory Service, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Lane Fox Clinical Respiratory Physiology Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Centre for Human and Applied Physiological Sciences (CHAPS), King's College London, London, UK
| | - Akanksha Mimi Malhotra
- Lane Fox Respiratory Service, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Georgios Kaltsakas
- Lane Fox Respiratory Service, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Lane Fox Clinical Respiratory Physiology Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Centre for Human and Applied Physiological Sciences (CHAPS), King's College London, London, UK
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17
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Orr WC, Fass R, Sundaram SS, Scheimann AO. The effect of sleep on gastrointestinal functioning in common digestive diseases. Lancet Gastroenterol Hepatol 2020; 5:616-624. [DOI: 10.1016/s2468-1253(19)30412-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 09/25/2019] [Accepted: 11/12/2019] [Indexed: 02/07/2023]
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18
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Chen LD, Wu RH, Huang YZ, Chen MX, Zeng AM, Zhuo GF, Xu FS, Liao R, Lin QC. The role of ferroptosis in chronic intermittent hypoxia-induced liver injury in rats. Sleep Breath 2020; 24:1767-1773. [PMID: 32361960 DOI: 10.1007/s11325-020-02091-4] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 04/16/2020] [Accepted: 04/17/2020] [Indexed: 11/26/2022]
Abstract
PURPOSE Obstructive sleep apnea (OSA) has been related to an increased risk of liver injury. Ferroptosis is a form of programmed cell death implicated in multiple physiological and pathological processes. This study aimed to explore the role of ferroptosis in chronic intermittent hypoxia (CIH)-induced liver injury as well as to uncover the underlying mechanisms using a CIH rat model. METHODS Fourteen male Sprague-Dawley rats were randomly allocated to either the normal control (NC) (n = 7) or the CIH group (n = 7). Rats were exposed to intermittent hypoxia for 8 weeks in CIH group. Liver function, histological changes, and markers of oxidative stress were evaluated. The protein levels of hypoxia-inducible factor-1α, nuclear factor E2-related factor 2 (Nrf2), Acyl-CoA synthetase long-chain family member 4 (ACSL4), and glutathione peroxidase 4 (GPX4) in liver were examined by Western blot analysis. RESULTS CIH treatment caused significant increase of serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde (MDA). Liver MDA was significantly higher in CIH group than that in NC group. Histology showed that CIH treatment induced discernible swelled, disordered hepatocytes, necrosis, and infiltrated inflammatory cells. CIH treatment significantly reduced the expression of GPX4, while markedly up-regulated expression of ACSL4, indicating elevation in hepatic ferroptosis. In addition, the protein expression of Nrf2 in CIH group was significantly lower than that in NC group. CONCLUSIONS Ferroptosis played a crucial role in CIH-induced liver injury. The hepatic ferroptosis in CIH rat model might be mediated by the dysregulation of Nrf2. This highlights a potential therapeutic target for the treatment of OSA-related liver injury.
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Affiliation(s)
- Li-Da Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No 20, Chazhong road, Taijiang district, Fuzhou, Fujian Province, 350005, People's Republic of China
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China
| | - Run-Hua Wu
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People's Republic of China
| | - Yu-Zhen Huang
- Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China
| | - Meng-Xue Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No 20, Chazhong road, Taijiang district, Fuzhou, Fujian Province, 350005, People's Republic of China
| | - Ai-Ming Zeng
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No 20, Chazhong road, Taijiang district, Fuzhou, Fujian Province, 350005, People's Republic of China
| | - Gui-Feng Zhuo
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People's Republic of China
| | - Feng-Sheng Xu
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People's Republic of China
| | - Ran Liao
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People's Republic of China
| | - Qi-Chang Lin
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No 20, Chazhong road, Taijiang district, Fuzhou, Fujian Province, 350005, People's Republic of China.
- Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou, Fujian Province, People's Republic of China.
- Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China.
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19
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Mesarwi OA, Loomba R, Malhotra A. Obstructive Sleep Apnea, Hypoxia, and Nonalcoholic Fatty Liver Disease. Am J Respir Crit Care Med 2020; 199:830-841. [PMID: 30422676 DOI: 10.1164/rccm.201806-1109tr] [Citation(s) in RCA: 152] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Recent studies have demonstrated that obstructive sleep apnea (OSA) is associated with the development and evolution of nonalcoholic fatty liver disease (NAFLD), independent of obesity or other shared risk factors. Like OSA, NAFLD is a prevalent disorder associated with major adverse health outcomes: Patients with NAFLD may develop cirrhosis, liver failure, and hepatocellular carcinoma. One major finding that has emerged from these studies is that the OSA-NAFLD association is related to the degree of nocturnal hypoxemia in OSA. Animal models have therefore largely focused on intermittent hypoxia, a key manifestation of OSA, to shed light on the mechanisms by which OSA may give rise to the complex metabolic disturbances that are seen in NAFLD. Intermittent hypoxia leads to tissue hypoxia and can result in oxidative stress, mitochondrial dysfunction, inflammation, and overactivation of the sympathetic nervous system, among many other maladaptive effects. In such models, intermittent hypoxia has been shown to cause insulin resistance, dysfunction of key steps in hepatic lipid metabolism, atherosclerosis, and hepatic steatosis and fibrosis, each of which is pertinent to the development and/or progression of NAFLD. However, many intriguing questions remain unanswered: Principally, how aggressively should the clinician screen for NAFLD in patients with OSA, and vice versa? In this review, we attempt to apply the best evidence from animal and human studies to highlight the relationship between these two disorders and to advocate for further trials aimed at defining these relationships more precisely.
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Affiliation(s)
- Omar A Mesarwi
- 1 Division of Pulmonary, Critical Care, and Sleep Medicine
| | - Rohit Loomba
- 2 Division of Gastroenterology, Department of Medicine, and.,3 Department of Family Medicine and Public Health, University of California San Diego School of Medicine, La Jolla, California
| | - Atul Malhotra
- 1 Division of Pulmonary, Critical Care, and Sleep Medicine
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20
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Chen Q, Chen LD, Chen MX, Wu YH, Zeng HX, Hu MF, Zhang WL, Zheng YF, Lin QC. The effect of continuous positive airway pressure on circulating malondialdehyde among obstructive sleep apnea patients: a meta-analysis. Sleep Breath 2019; 24:1407-1415. [PMID: 31873838 DOI: 10.1007/s11325-019-01998-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 11/11/2019] [Accepted: 12/09/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND Obstructive sleep apnea (OSA) has been demonstrated to be associated with an increase of oxidative stress. However, whether circulating malondialdehyde (MDA), a widely used biomarker of oxidative stress, could be reduced by the treatment of OSA by continuous positive airway pressure (CPAP) is debated. The present meta-analysis was performed to determine the effect of CPAP treatment on circulating MDA among patients with OSA. METHODS A systematic search of PubMed, Embase, and Web of Science was performed for literature covering the period between 1967 and August 2019. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy. RESULTS A total of 10 studies with 220 patients were included in this meta-analysis. A significant decrease in circulating MDA was observed after CPAP treatment (SMD = 1.164, 95% CI = 0.443 to 1.885, z = 3.16, p = 0.002) in OSA patients. Subgroup analyses revealed that CPAP therapy was associated with a significant decrease of circulating MDA in elder (SMD = 1.629, 95% CI = 0.265 to 2.994, z = 2.34, p = 0.019), more obese patients (SMD = 0.954, 95% CI = 0.435 to 1.473, z = 3.61, p = 0.000), more severe OSA patients (SMD = 0.879, 95% CI = 0.421 to 1.336, z = 3.76, p = 0.000), patients with therapeutic duration ≥ 3 months (SMD = 1.867, 95% CI = 0.563 to 3.172, z = 2.80, p = 0.005), and patients with good compliance (SMD = 1.004, 95% CI = 0.703 to 1.305, z = 6.54, p = 0.000). CONCLUSIONS This meta-analysis suggested that CPAP therapy exerted significant lowering effects on circulating MDA, especially in elder, more obese, and more severe OSA patients and patients with good compliance as well as longer duration of CPAP application.
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Affiliation(s)
- Qin Chen
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People's Republic of China
| | - Li-Da Chen
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China
| | - Meng-Xue Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No 20, Chazhong road, Taijiang district, Fuzhou, 350005, Fujian Province, People's Republic of China
| | - Yan-Hua Wu
- Medical Intensive Care Unit, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China
| | - Hui-Xue Zeng
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China
| | - Miao-Fen Hu
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China
| | - Wei-Liang Zhang
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China
| | - Yi-Feng Zheng
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China
| | - Qi-Chang Lin
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No 20, Chazhong road, Taijiang district, Fuzhou, 350005, Fujian Province, People's Republic of China. .,Fujian Provincial Sleep-disordered Breathing Clinic Center, Fuzhou, Fujian Province, People's Republic of China. .,Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China.
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21
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NAFLD and Extra-Hepatic Comorbidities: Current Evidence on a Multi-Organ Metabolic Syndrome. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16183415. [PMID: 31540048 PMCID: PMC6765902 DOI: 10.3390/ijerph16183415] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/06/2019] [Accepted: 09/08/2019] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its incidence is definitely increasing. NAFLD is a metabolic disease with extensive multi-organ involvement, whose extra-hepatic manifestations include type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, chronic kidney disease, osteoporosis, and polycystic ovarian syndrome. Recently, further evidence has given attention to pathological correlations not strictly related to metabolic disease, also incorporating in this broad spectrum of systemic involvement hypothyroidism, psoriasis, male sexual dysfunction, periodontitis, and urolithiasis. The most common cause of mortality in NAFLD is represented by cardiovascular disease, followed by liver-related complications. Therefore, clinicians should learn to screen and initiate treatment for these extra-hepatic manifestations, in order to provide appropriate multidisciplinary assessments and rigorous surveillance. This review evaluates the current evidence regarding extra-hepatic associations of NAFLD, focusing on the pathogenic hypothesis and the clinical implications.
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Mashaqi S, Badr MS. The Impact of Obstructive Sleep Apnea and Positive Airway Pressure Therapy on Metabolic Peptides Regulating Appetite, Food Intake, Energy Homeostasis, and Systemic Inflammation: A Literature Review. J Clin Sleep Med 2019; 15:1037-1050. [PMID: 31383242 DOI: 10.5664/jcsm.7890] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 04/04/2019] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Sleep-related breathing disorders are very common and highly associated with many comorbid diseases. They have many metabolic consequences that impact appetite, energy expenditure, and systemic inflammation. These consequences are mediated through peptides (eg, ghrelin, leptin, adiponectin, resistin, apelin, obestatin, and neuropeptide Y). METHODS We searched the literature (PubMed) for sleep-disordered breathing (SDB) and metabolic peptides and included 15, 22, 14, 4 and 2 articles for ghrelin, leptin, adiponectin, resistin, and apelin respectively. RESULTS Our review of the published literature suggests that leptin levels seem to correlate with body mass index and adiposity rather than obstructive sleep apnea. Conversely, levels of adiponectin and ghrelin are influenced by obstructive sleep apnea alone. Finally, resistin and apelin seem to be not correlated with obstructive sleep apnea. Regarding positive airway pressure (PAP) impact, it seems that PAP therapy affected the levels of these peptides (mainly ghrelin). CONCLUSIONS There is significant controversy in the literature regarding the impact of SDB and PAP therapy on these metabolic peptides. This could be due to the lack of randomized clinical trials and the variability of the methodology used in these studies. Further research is needed to assess the impact of SDB and PAP therapy on the levels of these peptides and whether this impact is also related to body mass index and body fat composition.
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Affiliation(s)
- Saif Mashaqi
- Division of Sleep Medicine, University of North Dakota School of Medicine - Sanford Health, Fargo, North Dakota
| | - M Safwan Badr
- Department of Internal Medicine, Wayne State University, Detroit, Michigan
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Abstract
Nonalcoholic fatty liver disease (NAFLD), a disorder of altered metabolic pathways, is increasing worldwide. Recent studies established obstructive sleep apnea (OSA) and chronic intermittent hypoxia (CIH) as NAFLD risk factors. Studies have ascertained that CIH is independently related to NAFLD. Continuous positive airway pressure (CPAP) shows inconsistent results regarding its efficacy in improving NAFLD. Observational, longer duration CPAP therapy studies have shown positive outcomes, whereas shorter duration, randomized controlled trials have shown no benefit. A multifaceted approach to NAFLD management with sufficiently longer duration of CPAP therapy may be beneficial in patients with moderate to severe OSA.
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Affiliation(s)
- Malav P Parikh
- Department of Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, M2 Annex, Cleveland, OH 44114, USA
| | - Niyati M Gupta
- Department of Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, M2 Annex, Cleveland, OH 44114, USA
| | - Arthur J McCullough
- Department of Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, M2 Annex, Cleveland, OH 44114, USA; Department of Inflammation and Immunity, Cleveland Clinic Lerner College of Medicine, Case Western University, Cleveland, OH 44195, USA.
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Kim D, Ahmed A, Kushida C. Continuous Positive Airway Pressure Therapy on Nonalcoholic Fatty Liver Disease in Patients With Obstructive Sleep Apnea. J Clin Sleep Med 2018; 14:1315-1322. [PMID: 30092894 DOI: 10.5664/jcsm.7262] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 04/04/2018] [Indexed: 12/22/2022]
Abstract
STUDY OBJECTIVES Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD) and related advanced fibrosis. We studied the treatment of OSA with continuous positive airway pressure (CPAP) in a population with NAFLD. METHODS Using an institutional database (2010-2014), we identified patients with NAFLD and OSA and studied changes in serum aminotransferases before and after CPAP use. We defined suspected NAFLD (sNAFLD) as serum alanine aminotransferase (ALT) > 30 U/L for men and > 19 U/L for women in the absence of known causes of chronic liver disease. The aspartate aminotransferase (AST) to platelet ratio index (APRI) was used to determine significant fibrosis. Consistent CPAP use for more than 3 months with adequate adherence parameters defined good adherence. RESULTS Of 351 patients with OSA on CPAP treatment, majority (mean age 57.6 years, 59.3% male) had abnormal ALT, and 89.4% met the criteria for sNAFLD. The prevalence of sNAFLD was higher among patients with moderate to severe OSA (90.6%) versus mild OSA (86.3%). There was a statistically significant improvement in AST, ALT, and APRI with CPAP therapy (all P < .01). There was an apparent dose-response relationship: patients with good adherence to CPAP showed a significantly larger decrease in AST and ALT than did those with poor adherence (P < .01). Multivariable logistic regression analysis showed CPAP treatment with adequate adherence (odds ratio = 3.93, 95% confidence interval = 1.29-11.94) was an independent predictor of regression of sNAFLD after adjusting for obesity class and severity of OSA. CONCLUSIONS OSA treatment with CPAP was associated with significant biochemical improvement and reduction in NAFLD-related fibrosis.
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Affiliation(s)
- Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Clete Kushida
- Division of Sleep Medicine, Stanford Hospital and Clinics, Redwood City, California
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Treating Obstructive Sleep Apnea and Chronic Intermittent Hypoxia Improves the Severity of Nonalcoholic Fatty Liver Disease in Children. J Pediatr 2018; 198:67-75.e1. [PMID: 29752170 DOI: 10.1016/j.jpeds.2018.03.028] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 02/27/2018] [Accepted: 03/14/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To determine the effects of treating obstructive sleep apnea/nocturnal hypoxia on pediatric nonalcoholic fatty liver disease (NAFLD) severity and oxidative stress. STUDY DESIGN Biopsy proven participants (n = 9) with NAFLD and obstructive sleep apnea/hypoxia were studied before and after treatment with continuous positive airway pressure (CPAP) for sleep disordered breathing, including laboratory testing and markers of oxidative stress, urine F(2)-isoprostanes. RESULTS Adolescents (age 11.5 ± 1.2 years; body mass index, 29.5 ± 3.8 kg/m2) with significant NAFLD (mean histologic necroinflammation grade, 2.3 ± 0.9; fibrosis stage, 1.4 ± 1.3; NAFLD Activity Score summary, 4.8 ± 1.6) had obstructive sleep apnea/hypoxia by polysomnography. At baseline, they had severe obstructive sleep apnea/hypoxia, elevated aminotransferases, the metabolic syndrome, and significant oxidative stress (high F(2)-isoprostanes). Obstructive sleep apnea/hypoxia was treated with home CPAP for a mean 89 ± 62 days. Although body mass index increased, obstructive sleep apnea/hypoxia severity improved on CPAP and was accompanied by reduced alanine aminotransferase, metabolic syndrome markers, and F(2)-isoprostanes. CONCLUSIONS This study provides strong evidence that treatment of obstructive sleep apnea/nocturnal hypoxia with CPAP in children with NAFLD may reverse parameters of liver injury and reduce oxidative stress. These data also suggest CPAP as a new therapy to prevent progression of NAFLD in those children with obesity found to have obstructive sleep apnea/nocturnal hypoxia.
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Bajantri B, Lvovsky D. A Case of Concomitant Obstructive Sleep Apnea and Non-Alcoholic Steatohepatitis Treated With CPAP Therapy. Gastroenterology Res 2018; 11:252-259. [PMID: 29915639 PMCID: PMC5997478 DOI: 10.14740/gr1033w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 05/09/2018] [Indexed: 12/12/2022] Open
Abstract
Obstructive sleep apnea syndrome is a disorder of sleep breathing that is a result of recurrent and intermittent hypoxia during sleep induced by the repeated partial or complete collapse of the upper airway, eventually causing chronic intermittent hypoxia. Non-alcoholic fatty liver disease is divided into non-alcoholic fatty liver and non-alcoholic steatohepatitis. Animal and human studies showed that obesity is associated with chronic liver hypoxia, even in the presence of systemic normoxia causing inflammation and release of cytokines. A "two-hit" model has been proposed. The first hit is characterized by insulin resistance and excess hepatic lipid accumulation secondary to abnormal fatty acid metabolism. Oxidative stress and inflammation are thought to comprise the second hit. Gold standard for the diagnosis of non-alcoholic steatohepatitis is a liver biopsy. Many clinical scores and non-invasive tools are used for the diagnosis of non-alcoholic steatohepatitis. Conservative management with lifestyle modifications including diet, exercise and weight loss remains the therapy of choice today. We present a case report of a 39-year-old man who was diagnosed with concomitant non-alcoholic steatohepatitis and severe obstructive sleep apnea. He was started treatment with continuous positive airway pressure and demonstrated excellent adherence to therapy for 6 years, with concomitant obstructive sleep apnea and non-alcoholic steatohepatitis which reversed with prolonged optimal continuous positive airway pressure therapy. Physical examination remained unremarkable except for morbid obesity. His abdominal girth, as well as body mass index, remained unchanged. After 6 years of optimal continuous positive airway pressure therapy, liver enzymes and relevant lipid panel normalized, suggesting reversal of non-alcoholic steatohepatitis.
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Affiliation(s)
- Bharat Bajantri
- Division of Pulmonary Critical Care, Department of Medicine, Bronx Care Health System, Bronx, NY 10457, USA
| | - Dmitry Lvovsky
- Division of Pulmonary Critical Care, Department of Medicine, Bronx Care Health System, Bronx, NY 10457, USA.,Division of Pulmonary and Critical Care Medicine, Bronx Lebanon Hospital Center, Bronx, NY 10457, USA
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27
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Labarca G, Cruz R, Jorquera J. Continuous Positive Airway Pressure in Patients With Obstructive Sleep Apnea and Non-Alcoholic Steatohepatitis: A Systematic Review and Meta-Analysis. J Clin Sleep Med 2018; 14:133-139. [PMID: 29151428 DOI: 10.5664/jcsm.6900] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 09/14/2017] [Indexed: 12/13/2022]
Abstract
STUDY OBJECTIVES Several studies have reported an association between obstructive sleep apnea (OSA) and several extra-pulmonary issues, such as arterial hypertension and insulin resistance. In recent years, the associations between OSA, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis (NASH) have been published; however, there is a gap between experimental and clinical studies regarding the efficacy of continuous positive airway pressure (CPAP) treatment in patient populations with these conditions. This issue should be considered when deciding on CPAP treatment in patients with OSA, especially in patients with moderate OSA. METHODS We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) using the following databases: MEDLINE, Lilacs, and CENTRAL. Two independent reviewers performed the search, analysis, data extraction, and critical analysis. RESULTS From 622 identified studies, we included 5 RCTs that involved patients with OSA and NASH and who were treated with a CPAP device. After CPAP treatment, no changes in liver steatosis, liver fibrosis, and aminotransferase levels (alanine aminotransferase and aspartate aminotransferase) were found. Finally, the quality of evidence using the GRADE approach was low and very low for several outcomes. CONCLUSIONS According to the current analysis, no data regarding the efficacy of CPAP in patients with NASH are available to make recommendations. SYSTEMATIC REVIEW REGISTRATION PROSPERO; ID: CRD42015027981; URL: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42015027981.
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Affiliation(s)
- Gonzalo Labarca
- Universidad San Sebastián, Concepción, Chile.,Departamento de Medicina Interna, Complejo Asistencial Víctor Ríos Ruiz, Los Ángeles, Chile
| | - Rodrigo Cruz
- Gastroenterology, Hospital Dipreca, Santiago, Chile
| | - Jorge Jorquera
- Sleep Center and Respiratory Disease, Clinica Las Condes, Santiago, Chile
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Jin S, Jiang S, Hu A. Association between obstructive sleep apnea and non-alcoholic fatty liver disease: a systematic review and meta-analysis. Sleep Breath 2018; 22:841-851. [PMID: 29335916 DOI: 10.1007/s11325-018-1625-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 01/03/2018] [Accepted: 01/05/2018] [Indexed: 12/23/2022]
Abstract
The relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) has been an issue of great concern. The primary purpose of this study was to determine the influence of OSA on the levels of liver enzymes including alanine transaminase (ALT) and aspartate transaminase (AST). The secondary purpose was to estimate the effect of OSA on the histological lesions of NAFLD, such as steatosis, lobular inflammation, ballooning degeneration, fibrosis, as well as NAFLD activity score (NAS). A systematic literature review using PubMed, Cochrane Library, Embase, and Ovid technologies from January 2007 to April 2017 was performed, and 9 studies (2272 participants) that met the selection criteria were evaluated. The present study demonstrated that OSA was related to ALT levels, but no significant correlation was found with AST levels. The subgroup analysis showed that the severity of OSA was associated with ALT levels, not with AST levels. The meta-regression analysis showed that age, sex, homeostasis model assessment, diabetes mellitus, body mass index, and waist circumference did not have a significant effect on the levels of ALT and AST. OSA was also found to be significantly correlated with steatosis, lobular inflammation, ballooning degeneration, and fibrosis, but was not correlated with NAS. OSA was independently related to the development and progression of NAFLD in terms of liver enzyme level and histological alterations. Future studies should investigate the possible relevant mechanisms, thereby guiding the exploration of potential therapeutic implications to prevent the progression of disease.
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Affiliation(s)
- Shanshan Jin
- Ningbo University School of Medicine, Ningbo City, Zhejiang Province, China
| | - Suwen Jiang
- Institute of Liver Diseases, Ningbo No. 2 Hospital, 41 Xibei Street, Haishu District, Ningbo City, Zhejiang Province, 315010, China
| | - Airong Hu
- Ningbo University School of Medicine, Ningbo City, Zhejiang Province, China. .,Institute of Liver Diseases, Ningbo No. 2 Hospital, 41 Xibei Street, Haishu District, Ningbo City, Zhejiang Province, 315010, China.
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29
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Liu X, Miao Y, Wu F, Du T, Zhang Q. Effect of CPAP therapy on liver disease in patients with OSA: a review. Sleep Breath 2018; 22:963-972. [PMID: 29327118 DOI: 10.1007/s11325-018-1622-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 12/15/2017] [Accepted: 01/05/2018] [Indexed: 12/15/2022]
Abstract
Obstructive sleep apnea (OSA) may play an important role in the progression of nonalcoholic fatty liver disease (NAFLD).The effect of continuous positive airway pressure (CPAP) treatment, the first-line therapy for OSA, on liver disease in OSA patients is still debated. We provide this review of previous studies to summarize the effects of CPAP treatment on liver disease in OSA patients in aspects of liver function, liver steatosis, fibrosis, and incidence of liver disease. CPAP treatment may be beneficial to liver disease in subjects with OSA independent of metabolic risk factors, but a sufficiently long therapeutic duration (perhaps greater than 3 months) may be needed to achieve these positive effects. Though the mechanism of impact of CPAP treatment on liver in OSA patients is unclear, the influence of CPAP treatment on the factors of the "Two-hit" hypothesis (insulin resistance, fatty acids dysregulation, oxidative stress, and inflammation) may be a reasonable explanation.
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Affiliation(s)
- Xin Liu
- Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China
| | | | - Fan Wu
- Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China
| | - Tingting Du
- Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China
| | - Qiang Zhang
- Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China.
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Chen LD, Zhang LJ, Lin XJ, Qi JC, Li H, Wu Z, Xu QZ, Huang YP, Lin L. Association between continuous positive airway pressure and serum aminotransferases in patients with obstructive sleep apnea. Eur Arch Otorhinolaryngol 2017; 275:587-594. [PMID: 29224042 DOI: 10.1007/s00405-017-4840-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 12/04/2017] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Obstructive sleep apnea (OSA) has been suggested to be a potential contributing factor for nonalcoholic fatty liver disease (NAFLD). Studies on the association between continuous positive airway pressure (CPAP) and NAFLD in OSA patients are limited and controversial. OBJECTIVES The aim of this study was to assess the relationship between OSA and NAFLD and the effect of CPAP therapy on serum aminotransferase levels in OSA patients. METHODS A total of 160 consecutive patients who underwent standard polysomnography were enrolled. Blood samples were obtained in the morning after sleep for biological profile measurements. Non-invasive ultrasound techniques were used to assess liver steatosis and fibrosis. Within the OSA group, serum aminotransferases were detected before and after CPAP treatment. RESULTS Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, and liver steatosis score increased significantly with an increase in OSA severity. Stepwise multiple regression with liver steatosis score, ALT, AST as dependent variable, respectively, apnea-hypopnea index (β = 0.447, p = 0.020; β = 0.266, p = 0.001; β = 0.351, p = 0.020, respectively) significantly predicted the liver steatosis score, ALT, AST after adjustment for confounders. After 3 months of CPAP treatment, there was a significant decrease in both ALT (54.20 ± 24.34 vs. 46.52 ± 24.95, p = 0.000) and AST (31.82 ± 8.91 vs. 29.00 ± 8.34, p = 0.039). CONCLUSIONS OSA severity was independently associated with liver steatosis and elevation of serum aminotransferases. 3 months of CPAP therapy were associated with a statistically significant improvement on liver injury in OSA patients.
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Affiliation(s)
- Li-Da Chen
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No 59, Shenglixi road, Xiangcheng district, Zhangzhou, 363000, Fujian, People's Republic of China
| | - Liang-Ji Zhang
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No 59, Shenglixi road, Xiangcheng district, Zhangzhou, 363000, Fujian, People's Republic of China
| | - Xue-Jun Lin
- Department of Laboratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, People's Republic of China
| | - Jia-Chao Qi
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No 59, Shenglixi road, Xiangcheng district, Zhangzhou, 363000, Fujian, People's Republic of China
| | - Hao Li
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No 59, Shenglixi road, Xiangcheng district, Zhangzhou, 363000, Fujian, People's Republic of China
| | - Zhi Wu
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No 59, Shenglixi road, Xiangcheng district, Zhangzhou, 363000, Fujian, People's Republic of China
| | - Qiao-Zhen Xu
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No 59, Shenglixi road, Xiangcheng district, Zhangzhou, 363000, Fujian, People's Republic of China
| | - Ya-Ping Huang
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No 59, Shenglixi road, Xiangcheng district, Zhangzhou, 363000, Fujian, People's Republic of China
| | - Li Lin
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No 59, Shenglixi road, Xiangcheng district, Zhangzhou, 363000, Fujian, People's Republic of China.
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Toyama Y, Murase K, Azuma M, Hamada S, Tachikawa R, Tanizawa K, Handa T, Kubo T, Hitomi T, Oga T, Hirai T, Chin K. Impact of long-term continuous positive airway pressure on liver fat in male obstructive sleep apnea patients with fatty liver. Sleep Biol Rhythms 2017. [DOI: 10.1007/s41105-017-0133-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Gu C, Younas H, Jun JC. Sleep apnea: An overlooked cause of lipotoxicity? Med Hypotheses 2017; 108:161-165. [PMID: 29055392 DOI: 10.1016/j.mehy.2017.09.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Accepted: 09/08/2017] [Indexed: 02/07/2023]
Abstract
Obstructive sleep apnea (OSA) is a common sleep disorder associated with diabetes and cardiovascular disease. However, the mechanisms by which OSA causes cardiometabolic dysfunction are not fully elucidated. OSA increases plasma free fatty acids (FFA) during sleep, reflecting excessive adipose tissue lipolysis. In animal studies, intermittent hypoxia simulating OSA also increases FFA, and the increase is attenuated by beta-adrenergic blockade. In other contexts, excessive plasma FFA can lead to ectopic fat accumulation, insulin resistance, vascular dysfunction, and dyslipidemia. Herein, we propose that OSA is a cause of excessive adipose tissue lipolysis contributing towards systemic "lipotoxicity". Since visceral and upper-body obesity contributes to OSA pathogenesis, OSA-induced lipolysis may further aggravate the consequences of this metabolically harmful state. If this hypothesis is correct, then OSA may represent a reversible risk factor for cardio-metabolic dysfunction, and this risk might be mitigated by preventing OSA-induced lipolysis during sleep.
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Affiliation(s)
- Chenjuan Gu
- Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haris Younas
- Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Jonathan C Jun
- Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
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