|
1
|
Wang L, Liu H, Zhou L, Zheng P, Li H, Zhang H, Liu W. Association of Obstructive Sleep Apnea with Nonalcoholic Fatty Liver Disease: Evidence, Mechanism, and Treatment. Nat Sci Sleep 2024; 16:917-933. [PMID: 39006248 PMCID: PMC11244635 DOI: 10.2147/nss.s468420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/22/2024] [Indexed: 07/16/2024] Open
Abstract
Obstructive sleep apnea (OSA), a common sleep-disordered breathing condition, is characterized by intermittent hypoxia (IH) and sleep fragmentation and has been implicated in the pathogenesis and severity of nonalcoholic fatty liver disease (NAFLD). Abnormal molecular changes mediated by IH, such as high expression of hypoxia-inducible factors, are reportedly involved in abnormal pathophysiological states, including insulin resistance, abnormal lipid metabolism, cell death, and inflammation, which mediate the development of NAFLD. However, the relationship between IH and NAFLD remains to be fully elucidated. In this review, we discuss the clinical correlation between OSA and NAFLD, focusing on the molecular mechanisms of IH in NAFLD progression. We meticulously summarize clinical studies evaluating the therapeutic efficacy of continuous positive airway pressure treatment for NAFLD in OSA. Additionally, we compile potential molecular biomarkers for the co-occurrence of OSA and NAFLD. Finally, we discuss the current research progress and challenges in the field of OSA and NAFLD and propose future directions and prospects.
Collapse
Affiliation(s)
- Lingling Wang
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Huiguo Liu
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Ling Zhou
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Pengdou Zheng
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Hai Li
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Huojun Zhang
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Wei Liu
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| |
Collapse
|
|
2
|
Terziev D, Terzieva D. Experimental Data on the Role of Melatonin in the Pathogenesis of Nonalcoholic Fatty Liver Disease. Biomedicines 2023; 11:1722. [PMID: 37371817 DOI: 10.3390/biomedicines11061722] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/11/2023] [Accepted: 06/14/2023] [Indexed: 06/29/2023] Open
Abstract
Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide, its complex pathogenesis remains incompletely understood. The currently stated hypotheses cannot fully clarify the interrelationships between individual pathogenetic mechanisms of the disease. No appropriate health strategies have been developed for treating NAFLD. NAFLD is characterized by an accumulation of triglycerides in hepatic cells (steatosis), with the advanced form known as nonalcoholic steatohepatitis. In the latter, superimposed inflammation can lead to fibrosis. There are scientific data on NAFLD's association with components of metabolic syndrome. Hormonal factors are thought to play a role in the development of metabolic syndrome. Endogenous melatonin, an indoleamine hormone synthesized by the pineal gland mainly at night, is a powerful chronobiotic that probably regulates metabolic processes and has antioxidant, anti-inflammatory, and genomic effects. Extrapineal melatonin has been found in various tissues and organs, including the liver, pancreas, and gastrointestinal tract, where it likely maintains cellular homeostasis. Melatonin exerts its effects on NAFLD at the cellular, subcellular, and molecular levels, affecting numerous signaling pathways. In this review article, we discuss the experimental scientific data accumulated on the involvement of melatonin in the intimate processes of the pathogenesis of NAFLD.
Collapse
Affiliation(s)
- Dimitar Terziev
- Second Department of Internal Medicine, Gastroenterology Section, Faculty of Medicine, Medical University, 4002 Plovdiv, Bulgaria
| | - Dora Terzieva
- MDL "Bioiv", Medical University, 4002 Plovdiv, Bulgaria
| |
Collapse
|
|
3
|
The association between obstructive sleep apnea and lung nodule, carcinoembryonic antigen. Eur Arch Otorhinolaryngol 2023; 280:2025-2032. [PMID: 36481978 DOI: 10.1007/s00405-022-07776-y] [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: 09/10/2022] [Accepted: 12/01/2022] [Indexed: 12/13/2022]
Abstract
PURPOSE The association between obstructive sleep apnea (OSA) and cancer risks gaining more and more attention. Data on the association between OSA and lung cancer risk are limited. This study is to investigate whether a link exists between low-dose computed tomography (LDCT) scanning of the chest findings, carcinoembryonic antigen (CEA) and OSA in patients suspected of OSA. METHODS The cross-sectional study included patients aged 18 years or older who underwent continuous nocturnal polysomnography at our sleep center between February 2019 and November 2020. All subjects underwent chest LDCT and CEA. Patients with an apnea-hypopnea index (AHI) of ≥ 15/h were classified as clinically significant OSA group, whereas patients with an AHI < 15/h were classified as control group. RESULTS A total of 277 patients were enrolled in the study. 176 patients were categorized into the OSA group, while 101 patients were categorized into the control group. There is no relationship between any OSA-related parameter and presence of lung nodule or presence of ≥ 6 mm lung nodule in the binary logistic regression analysis. OSA group demonstrated a significant higher value of CEA than control group. Stepwise multiple linear regression analysis showed that lowest O2 saturation (β = - 0.256, p < 0.001), smoking status (β = 0.156, p = 0.007) and age (β = 0.153, p = 0.008) were independent predictors of elevated CEA. CONCLUSIONS OSA was independently related to the elevated of serum CEA level, but not with presence of pulmonary nodule or ≥ 6 mm pulmonary nodule in LDCT. Further well-designed longitudinal studies with pathology available are needed to identify the association between OSA and risk of lung cancer.
Collapse
|
|
4
|
Chen LD, Huang JF, Lin XJ, Huang YP, Xu QZ, Chen GP, Lin QC. Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury. Front Physiol 2022; 13:972407. [PMID: 36187780 PMCID: PMC9515621 DOI: 10.3389/fphys.2022.972407] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 08/23/2022] [Indexed: 11/13/2022] Open
Abstract
Intermittent hypoxia (IH) is a prominent feature of obstructive sleep apnea (OSA) which is increasingly recognized as a key risk factor for liver injury. Circular RNAs (circRNAs) has been suggested to act as a regulator of multiple biological processes. However, there is no study evaluating circRNAs alterations and potential role of circRNAs in OSA-related liver injury. The present study aimed to investigate circRNA expression profiles in vitro model of IH-induced liver injury, as well as potential functional characterization of the differentially expressed circRNAs (DE circRNAs). BRL-3A cells were exposed to IH or normoxia. Cell apoptosis and cell viability were evaluated using flow cytometry and cell counting kit-8, respectively. The expression profile of circRNAs was depicted by circRNA sequencing. The selected circRNAs were verified by quantitative real-time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were employed to predict DE circRNAs functions. The circRNA-miRNA-mRNA regulatory network was constructed. IH treatment caused cell injury in BRL-3A cells. 98 circRNAs were identified as being dysregulated in IH-treated BRL-3A cells. Among them, 58 were up-regulated and 40 were down-regulated. Go and KEGG analyses suggested that the DE circRNAs were predominantly enriched in the biological process such as positive regulation of NF−kappaB transcription factor activity and pathways such as circadian entrainment, Wnt signaling pathway, MAPK signaling pathway, and protein export. 3 up-regulated circRNAs and 3 down-regulated circRNAs with high number of back-splicing sites were chosen for qRT-PCR validation and were consistent with the sequencing data. CircRNA1056 and circRNA805 were predicted to interact with microRNAs that might thereby regulate downstream genes. The study characterized a profile of dysregulated circRNAs in IH-induced BRL-3A cell injury. DE circRNAs may play vital roles in the pathophysiology of IH-induced liver injury. Our findings provide preliminary support for further research in mechanisms and a new theory for the pathogenesis of OSA-related liver injury.
Collapse
Affiliation(s)
- Li-Da Chen
- Department of Respiratory and Critical Care 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
- Fujian Provincial Sleep-disordered Breathing Clinic Center, Fuzhou, China
- Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, China
| | - Xue-Jun Lin
- Department of Laboratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Ya-Ping Huang
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Qiao-Zhen Xu
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Gong-Ping Chen
- 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
- *Correspondence: Gong-Ping Chen, ; Qi-Chang Lin,
| | - 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
- *Correspondence: Gong-Ping Chen, ; Qi-Chang Lin,
| |
Collapse
|
|
5
|
Ji Y, Liang Y, Mak JC, Ip MS. Obstructive sleep apnea, intermittent hypoxia and non-alcoholic fatty liver disease. Sleep Med 2022; 95:16-28. [DOI: 10.1016/j.sleep.2022.04.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 04/10/2022] [Accepted: 04/11/2022] [Indexed: 12/15/2022]
|
|
6
|
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.
Collapse
Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
| |
Collapse
|
|
7
|
Lian N, Wu J, Wang B, Lin S, Huang J, Chen J, Lin Q. Risk Factors of Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Non-Obese Patients with Obstructive Sleep Apnea. Nat Sci Sleep 2022; 14:2143-2149. [PMID: 36507312 PMCID: PMC9733560 DOI: 10.2147/nss.s388203] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 11/24/2022] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Liver injury in non-obese obstructive sleep apnea (OSA) patients has received much attention in recent years. This study aimed to investigate risk factors of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis in non-obese patients with OSA. METHODS A retrospective study was conducted in the Sleep Center of the First Affiliated Hospital of Fujian Medical University. All consecutive non-obese patients with suspected sleep apnea admitted to the center were enrolled. The clinical characteristics of patients with simple snoring and with different severity OSA were compared. Multivariate logistic regression models were used to analyze the risk factors of NAFLD and liver fibrosis. RESULTS A total of 410 patients were enrolled. The levels of triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased with the aggravation of OSA (All p<0.05). Among non-obese patients with OSA, 17 (5%) were diagnosed with liver fibrosis and 228 (65%) with NAFLD; Apnea‑hyponea index (AHI) was an independent predictor for NAFLD and liver fibrosis [OR (95% CI): 1.02 (1.00-1.03), 1.04 (1.00-1.07), both p<0.05]; hypertriglyceridemia was an independent predictor for NAFLD [OR (95% CI): 1.13 (1.12-1.99), p<0.05]. CONCLUSION NAFLD and liver fibrosis were common in non-obese OSA patients and the severity of OSA was an independent risk factor for them.
Collapse
Affiliation(s)
- Ningfang Lian
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University; Fujian Provincial Sleep-Disordered Breathing Clinic Center; National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University; Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People's Republic of China
| | - Jiawei Wu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University; Fujian Provincial Sleep-Disordered Breathing Clinic Center; National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University; Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People's Republic of China
| | - Biying Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University; Fujian Provincial Sleep-Disordered Breathing Clinic Center; National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University; Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People's Republic of China
| | - Su Lin
- Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
| | - Jiefeng Huang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University; Fujian Provincial Sleep-Disordered Breathing Clinic Center; National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University; Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People's Republic of China
| | - Jia Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University; Fujian Provincial Sleep-Disordered Breathing Clinic Center; National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University; Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People's Republic of China
| | - Qichang Lin
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University; Fujian Provincial Sleep-Disordered Breathing Clinic Center; National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University; Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People's Republic of China
| |
Collapse
|
|
8
|
Perez-Carreras M, Casis-Herce B, Rivera R, Fernandez I, Martinez-Montiel P, Villena V. Non-alcoholic fatty liver disease in patients with intestinal, pulmonary or skin diseases: Inflammatory cross-talk that needs a multidisciplinary approach. World J Gastroenterol 2021; 27:7113-7124. [PMID: 34887631 PMCID: PMC8613653 DOI: 10.3748/wjg.v27.i41.7113] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/04/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently considered the most common cause of liver disease. Its prevalence is increasing in parallel with the obesity and type 2 diabetes mellitus (DM2) epidemics in developed countries. Several recent studies have suggested that NAFLD may be the hepatic manifestation of a systemic inflammatory metabolic disease that also affects other organs, such as intestine, lungs, skin and vascular endothelium. It appears that local and systemic proinflammatory/anti-inflammatory cytokine imbalance, together with insulin resistance and changes in the intestinal microbiota, are pathogenic mechanisms shared by NAFLD and other comorbidities. NAFLD is more common in patients with extrahepatic diseases such as inflammatory bowel disease (IBD), obstructive syndrome apnea (OSA) and psoriasis than in the general population. Furthermore, there is evidence that this association has a negative impact on the severity of liver lesions. Specific risk characteristics for NAFLD have been identified in populations with IBD (i.e. age, obesity, DM2, previous bowel surgery, IBD evolution time, methotrexate treatment), OSA (i.e. obesity, DM2, OSA severity, increased transaminases) and psoriasis (i.e. age, metabolic factors, severe psoriasis, arthropathy, elevated transaminases, methotrexate treatment). These specific phenotypes might be used by gastroenterologists, pneumologists and dermatologists to create screening algorithms for NAFLD. Such algorithms should include non-invasive markers of fibrosis used in NAFLD to select subjects for referral to the hepatologist. Prospective, controlled studies in NAFLD patients with extrahepatic comorbidities are required to demonstrate a causal relationship and also that appropriate multidisciplinary management improves these patients’ prognosis and survival.
Collapse
Affiliation(s)
- Mercedes Perez-Carreras
- Gastroenterology and Hepatology Unit, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
| | - Begoña Casis-Herce
- Gastroenterology and Hepatology Unit, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
| | - Raquel Rivera
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
- Dermatology Department, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
| | - Inmaculada Fernandez
- Gastroenterology and Hepatology Unit, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
| | - Pilar Martinez-Montiel
- Gastroenterology and Hepatology Unit, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
| | - Victoria Villena
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
- Pneumology Service, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
| |
Collapse
|
|
9
|
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.
Collapse
|
|
10
|
Sukahri S, Mohamed Shah FZ, Ismail AI, Koshy M, Johari B, Mohd Razali M, Abdul Rahman TH, Isa MR, Abdul Ghani R. Significantly higher atherosclerosis risks in patients with obstructive sleep apnea and non-alcoholic fatty liver disease. PLoS One 2021; 16:e0253298. [PMID: 34191823 PMCID: PMC8244858 DOI: 10.1371/journal.pone.0253298] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 06/01/2021] [Indexed: 01/11/2023] Open
Abstract
INTRODUCTION There is limited data on the relationship between Obstructive Sleep Apnea (OSA) and Non-Alcoholic Fatty Liver Disease (NAFLD), each associated with increased cardiovascular risk. This study aimed to determine the relationships between severity of OSA, degree of steatosis in NAFLD and cardiovascular risk via CIMT and atherosclerosis markers ie intracellular adhesion molecule-1 (ICAM-1) an Lipoprotein-a (Lp(a)) in a group of patients with OSA. MATERIALS AND METHODS This was a cross-sectional, single center study. A total of 110 subjects between 18 to 65 years of age and diagnosed with OSA following sleep study examinations were recruited. Exclusion criteria included seropositive Hepatitis B or Hepatitis C, and significant alcohol intake. RESULT The prevalence of NAFLD was 81.8%. The mean CIMT (0.08±0.03 vs 0.06±0.01 cm, p = 0.001), ICAM-1 (334.53±72.86 vs 265.46±102.92 ng/mL, p = 0.001) and Lp(a) (85.41±52.56 vs 23.55±23.66 nmol/L, p<0.001) were significantly higher in the NAFLD group compared to the non-NAFLD group. Comparisons between the different groups showed significantly increasing levels of CIMT, ICAM-1 and Lp(a), lowest within the non-NAFLD, followed by the NAFLD 1 and NAFLD 2+3 groups. There was a significant positive correlation between degree of steatosis and the severity of OSA (r = 0.453, p<0.001). Logistic regression analysis revealed that patients with apnea/hypopnea index (AHI) of >30 were 52.77 (CI 6.34, 439.14) times more likely to have NAFLD compared to those with mild AHI (p<0.001). CONCLUSION The prevalence of NAFLD is alarmingly high in this group of OSA patients. The degree of steatosis in patients with NAFLD was significantly correlated with severity of OSA, CIMT measurements, ICAM-1 and Lp(a). Our findings underscore screening for NAFLD in patients with OSA to ensure prompt risk stratification and management.
Collapse
Affiliation(s)
- Samshol Sukahri
- Faculty of Medicine, Dept of Internal Medicine, Universiti Teknologi MARA (UiTM), Sg Buloh, Selangor, Malaysia
| | | | - Ahmad Izuanuddin Ismail
- Faculty of Medicine, Dept of Internal Medicine, Universiti Teknologi MARA (UiTM), Sg Buloh, Selangor, Malaysia
| | - Marymol Koshy
- Faculty of Medicine, Dept of Radiology, Universiti Teknologi MARA (UiTM), Sg Buloh, Selangor, Malaysia
| | - Bushra Johari
- Faculty of Medicine, Dept of Radiology, Universiti Teknologi MARA (UiTM), Sg Buloh, Selangor, Malaysia
| | - Mazuin Mohd Razali
- Faculty of Medicine, Dept of Radiology, Universiti Teknologi MARA (UiTM), Sg Buloh, Selangor, Malaysia
| | | | - Mohamad Rodi Isa
- Faculty of Medicine, Dept of Public Health, Universiti Teknologi MARA (UiTM), Sg Buloh, Selangor, Malaysia
| | - Rohana Abdul Ghani
- Faculty of Medicine, Dept of Internal Medicine, Universiti Teknologi MARA (UiTM), Sg Buloh, Selangor, Malaysia
- Laboratory and Forensic Medicine (I-PPerForM), Institute of Pathology, Sg Buloh Campus, Universiti Teknologi MARA (UiTM), Selangor, Malaysia
| |
Collapse
|
|
11
|
Chen R, Huang ZW, Lin XF, Lin JF, Yang MJ. Effect of continuous positive airway pressure on albuminuria in patients with obstructive sleep apnea: a meta-analysis. Sleep Breath 2021; 26:279-285. [PMID: 33990909 DOI: 10.1007/s11325-021-02393-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 04/27/2021] [Accepted: 04/28/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE A relationship between albuminuria and obstructive sleep apnea (OSA) has been documented in previous studies. Nevertheless, the impact of continuous positive airway pressure (CPAP) treatment on albuminuria in subjects with OSA is debated. This meta-analysis was carried out to investigate whether or not CPAP treatment affected urinary albumin-to-creatinine ratio (UACR) in subjects with OSA. METHODS A comprehensive literature search was conducted on Web of Science, Embase, and PubMed from January 1990 to December 2020. Information on patients' characteristics, features of the studies, and UACR of pre- and post-CPAP treatment was collected. For estimation of the pooled effects, standardized mean difference (SMD) was applied. RESULTS This meta-analysis included 6 articles and 211 subjects. The pooled analysis suggested that CPAP therapy exerted a favorable effect on the decrease of UACR in subjects with OSA (SMD = 0.415, 95% CI = 0.026 to 0.804, z = 2.09, p = 0.037). Subgroup analyses revealed that the CPAP treatment effect was not influenced by sample size, BMI, age, or AHI. CONCLUSION The present meta-analysis indicated that UACR was significantly reduced by CPAP therapy in subjects with OSA. Further well-designed randomized controlled trials with large sample size are required to confirm the benefits.
Collapse
Affiliation(s)
- Ru Chen
- Department of Urology, The First Hospital of Putian City, Putian, Fujian, China
| | - Zhi-Wei Huang
- Department of Otolaryngology, Quanzhou First Hospital Affiliated to Fujian Medical University, Dongjie Road, Licheng District, Quanzhou, Fujian, 362000, People's Republic of China.
| | - Xiao-Fen Lin
- Department of Cadre Ward, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China
| | - Jin-Fang Lin
- Department of Urology, The First Hospital of Putian City, Putian, Fujian, China
| | - Mei-Juan Yang
- Department of Obstetrics & Gynecology, Nanri Branch of the First Hospital of Putian City, Putian, Fujian, China
| |
Collapse
|
|
12
|
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.
Collapse
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
| |
Collapse
|
|
13
|
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.
Collapse
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
| |
Collapse
|
|
14
|
Abstract
Purpose of review Sleep is intimately involved in overall health and wellbeing. We provide a comprehensive report on the interplay between systemic diseases and sleep to optimize the outcomes of systemic disorders. Recent findings Spanning the categories of endocrinologic disorders, metabolic/toxic disturbances, renal, cardiovascular, pulmonary, gastrointestinal, infectious diseases, autoimmune disorders, malignancy, and critical illness, the review highlights the prevalent coexisting pathology of sleep across the spectrum of systemic disorders. Although it is rare that treating a sleep symptom can cure disease, attention to sleep may improve quality of life and may mitigate or improve the underlying disorder. Recent controversies in assessing the cardiovascular relationship with sleep have called into question some of the benefits of treating comorbid sleep disorders, thereby highlighting the need for an ongoing rigorous investigation into how sleep interplays with systemic diseases. Summary Systemic diseases often have sleep manifestations and this report will help the clinician identify key risk factors linking sleep disorders to systemic diseases so as to optimize the overall care of the patient.
Collapse
Affiliation(s)
- Eric M. Davis
- Division of Pulmonary and Critical Care, Department of Medicine, University of Virginia, Charlottesville, VA USA
| | - Chintan Ramani
- Division of Pulmonary and Critical Care, Department of Medicine, University of Virginia, Charlottesville, VA USA
| | - Mark Quigg
- Department of Neurology, University of Virginia, Charlottesville, VA USA
| |
Collapse
|
|
15
|
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: 37] [Impact Index Per Article: 7.4] [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.
Collapse
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.
| |
Collapse
|
|
16
|
Validation of fatty liver index and hepatic steatosis index for screening of non-alcoholic fatty liver disease in adults with obstructive sleep apnea hypopnea syndrome. Chin Med J (Engl) 2020; 132:2670-2676. [PMID: 31765354 PMCID: PMC6940109 DOI: 10.1097/cm9.0000000000000503] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a contributing factor for non-alcoholic fatty liver disease (NAFLD). Non-invasive algorithms including fatty liver index (FLI) and hepatic steatosis index (HSI) have been used as a screening test for NAFLD in epidemiologic studies. The aim of this study is to compare the diagnostic accuracy of FLI and HSI for NAFLD detection in adults with OSAHS. Methods: We enrolled consecutive adult subjects who were newly diagnosed with OSAHS from March 2016 to January 2018. NAFLD was diagnosed by ultrasonography. The accuracy and cut-off point of the FLI and HSI to detect NAFLD were assessed by analyzing the area under the receiver operating characteristic (AUROC) curve and the maximum Youden index analysis, respectively. Results: The 326 subjects were diagnosed as NAFLD according to ultrasound findings, while 105 subjects who had normal abdominal ultrasonography were grouped as controls. Both FLI and HSI values were significantly higher in patients with NAFLD compared with controls. The AUROC of FLI and HSI for predicting NAFLD was 0.802 (95% confidence interval [CI] 0.762–0.839) and 0.753 (95% CI 0.710–0.793), respectively. The AUROC of FLI was significantly higher than that of HSI (P = 0.0383). The optimal cut-off value of FLI and HSI was 60 (sensitivity 66% and specificity 80%) and 35 (sensitivity 81% and specificity 60%), respectively. Conclusions: Both FLI and HSI can serve as screening tools for NAFLD in OSAHS adults. The FLI shows better performance in diagnosing NAFLD than HSI. Trial registration: Chinese Clinical Trial Registry (No. ChiCTR-OOB-15007253), http://www.chictr.org.cn/showproj.aspx?proj=11606.
Collapse
|
|
17
|
Obstructive sleep apnea and liver injury in severely obese patients with nonalcoholic fatty liver disease. Sleep Breath 2020; 24:1515-1521. [PMID: 32002742 DOI: 10.1007/s11325-020-02018-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 12/26/2019] [Accepted: 01/15/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) are common in subjects with severe obesity. It has been suggested that insulin resistance and systemic inflammation may play a role in the development of nonalcoholic steatohepatitis (NASH), but the mechanisms remain controversial. The aim of this study was to explore the influence of OSA on liver injury and its potential mechanisms in severely obese patients with NAFLD. METHODS Severely obese patients requiring bariatric surgery were consecutively recruited between November 2017 and June 2018. Demographic, biochemical, liver ultrasound, and ambulatory polygraph data were collected. RESULTS One hundred fifty-three subjects with liver ultrasound-verified NAFLD were classified into three groups according to the apnea-hypopnea index (AHI). The level of serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) tended to increase with more severe OSA (P = 0.024 and P = 0.004, respectively). In the unadjusted analysis, both ALT and GGT were positively correlated with AHI, oxygen desaturation index, percentage of total sleep time spent with oxyhemoglobin saturation below 90%, male sex, homeostasis model assessment of insulin resistance (HOMA-IR), and total cholesterol, while liver enzymes were negatively related to lowest oxygen saturation. In multiple regression analysis, AHI (odds ratio (OR) = 1.052, P = 0.044) and HOMA-IR (OR = 1.135, P = 0.001) were independent risk factors for an elevated ALT level. High-sensitivity C-reactive protein (hs-CRP) was positively associated with BMI and GGT (r = 0.349 and r = 0.164 (P < 0.05), respectively), and no correlation was found between hs-CRP and AHI or other parameters of hypoxia. hs-CRP and GGT remained significantly correlated after adjusting for confounding parameters (OR = 2.509, P = 0.013). CONCLUSIONS OSA may play a role in liver injury among severely obese individuals with NAFLD. Insulin resistance and systemic inflammation were possible contributing factors in this process.
Collapse
|
|
18
|
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: 165] [Impact Index Per Article: 33.0] [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.
Collapse
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
| |
Collapse
|
|
19
|
Mohamed AS, Hosney M, Bassiony H, Hassanein SS, Soliman AM, Fahmy SR, Gaafar K. Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats. Sci Rep 2020; 10:378. [PMID: 31942001 PMCID: PMC6962368 DOI: 10.1038/s41598-019-57252-7] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 12/16/2019] [Indexed: 01/11/2023] Open
Abstract
Rodents are widely used for animal research in Egypt. Pentobarbital is the most common anesthetic agent; however overdoses may affect the experimental outcomes and limit the use of tissues. To investigate the effects of sodium pentobarbital overdoses during exsanguination, three groups (6 rats/group) of male and female rats were injected i.p. with 50, 100 and 150 mg/kg of sodium pentobarbital, then carotid exsanguination was performed immediately after loss of consciousness. Hypoxia-inducible factor 1-alpha (Hif1a) and tumor necrosis factor-alpha (Tnfa) mRNA expressions in liver and kidney organs were evaluated. As well as, serum aminotransferase activities (AST&ALT), glucose, urea, creatinine, malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) levels were determined. The histological alterations in liver, kidney and spleen were studied. It was found that Hif1a and Tnfa were significantly overexpressed in the studied organs and serum AST, glucose, creatinine and urea levels were significantly increased after sodium pentobarbital overdoses (100 and 150 mg/kg) compared to 50 mg/kg dose. Similarly, significant increase in MDA and GSH levels of liver, kidney and spleen were noticed. Results showed gender difference where Hif1a and Tnfa levels were significantly overexpressed at high dose of sodium pentobarbital of liver and kidney organs in female more than male rats. Since euthanasia protocol may influence the physiological variables and affect genes' expression, it is recommended to avoid sodium pentobarbital overdose during euthanasia as it may interfere with the biochemical, molecular and histological measurements.
Collapse
Affiliation(s)
- Ayman S Mohamed
- Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt
| | - Mohamed Hosney
- Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt
| | - Heba Bassiony
- Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt.
| | - Sarah S Hassanein
- Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt
| | - Amel M Soliman
- Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt
| | - Sohair R Fahmy
- Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt
| | - Khadiga Gaafar
- Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt
| |
Collapse
|
|
20
|
Trzepizur W, Boursier J, Berréhare A, Le Vaillant M, Andriantsitohaina R, Ducluzeau PH, Dubois S, Henni S, Abraham P, Calès P, Aubé C, Paisant A, Gagnadoux F. Obstructive sleep apnoea severity and liver steatosis measured by magnetic resonance imaging. Eur Respir J 2020; 55:13993003.01514-2019. [PMID: 31649063 DOI: 10.1183/13993003.01514-2019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 09/11/2019] [Indexed: 01/21/2023]
Affiliation(s)
- Wojciech Trzepizur
- Département de Pneumologie et Médecine du Sommeil, Centre Hospitalier Universitaire, Angers, France .,INSERM UMR 1063 SOPAM, Université d'Angers, Angers, France
| | - Jérôme Boursier
- Département d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Angers, France.,HIFIH, EA3859, Université d'Angers, Angers, France
| | - Anna Berréhare
- Département de Pneumologie et Médecine du Sommeil, Centre Hospitalier Universitaire, Angers, France
| | - Marc Le Vaillant
- Institut de Recherche en Santé Respiratoire des Pays de la Loire, Beaucouzé, France
| | | | - Pierre-Henri Ducluzeau
- Unité d'Endocrinologie-Diabétologie-Nutrition, Pole de Médecine, Centre Hospitalier Universitaire, Tours, France
| | - Séverine Dubois
- INSERM UMR 1063 SOPAM, Université d'Angers, Angers, France.,Département d'Endocrinologie, Diabétologie et Nutrition, Centre Hospitalier Universitaire, Angers, France
| | - Samir Henni
- Service de Médecine Vasculaire, Centre Hospitalier Universitaire, Angers, France.,Institut MITOVASC, UMR CNRS 6015, INSERM 1083, Université d'Angers, Angers, France
| | - Pierre Abraham
- Service de Médecine Vasculaire, Centre Hospitalier Universitaire, Angers, France.,Institut MITOVASC, UMR CNRS 6015, INSERM 1083, Université d'Angers, Angers, France
| | - Paul Calès
- Département d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Angers, France.,HIFIH, EA3859, Université d'Angers, Angers, France
| | - Christophe Aubé
- HIFIH, EA3859, Université d'Angers, Angers, France.,Département de Radiologie, Centre Hospitalier Universitaire, Angers, France
| | - Anita Paisant
- HIFIH, EA3859, Université d'Angers, Angers, France.,Département de Radiologie, Centre Hospitalier Universitaire, Angers, France
| | - Frédéric Gagnadoux
- Département de Pneumologie et Médecine du Sommeil, Centre Hospitalier Universitaire, Angers, France.,INSERM UMR 1063 SOPAM, Université d'Angers, Angers, France
| | | |
Collapse
|
|
21
|
Maâlej S, Jedidi S, Hannachi H, Gharsalli H, Sahnoun I, Neji H, El Gharbi L. Prévalence et facteurs de risque de stéatose hépatique chez les adultes tunisiens atteints de syndrome d’apnées hypopnées obstructives du sommeil. Rev Mal Respir 2020; 37:8-14. [DOI: 10.1016/j.rmr.2019.11.643] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 10/07/2019] [Indexed: 11/24/2022]
|
|
22
|
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: 93] [Impact Index Per Article: 15.5] [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.
Collapse
|
|
23
|
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.
Collapse
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.
| |
Collapse
|
|
24
|
Xin L, Fan W, Tingting D, Zuoming S, Qiang Z. 4-phenylbutyric acid attenuates endoplasmic reticulum stress-mediated apoptosis and protects the hepatocytes from intermittent hypoxia-induced injury. Sleep Breath 2018; 23:711-717. [PMID: 30324548 DOI: 10.1007/s11325-018-1739-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 09/27/2018] [Accepted: 10/08/2018] [Indexed: 12/15/2022]
Abstract
PURPOSE To investigate the effect of 4-phenylbutyric acid (4-PBA) on intermittent hypoxia (IH)-induced liver cell injury and to clarify the underlying mechanisms. METHODS L02 cells (normal human liver cells) were cultured in normoxic condition or subjected to intermittent hypoxia for 4, 8, and 12 h. A part of hypoxia-treated L02 cells was applied with 4-PBA 1 h before exposure to hypoxia. The effect of 4-PBA on liver injury, hepatocyte apoptosis, endoplasmic reticulum stress (ERS), and PERK-eIFa2-ATF4-CHOP apoptotic pathway was investigated. RESULTS (1) IH caused apoptosis in hepatocyte; (2) IH caused ERS in hepatocyte; (3) IH caused hepatic injury; (4) 4-PBA attenuated IH-induced liver cell injury; (5) 4-PBA protected liver cell from IH-induced apoptosis; (6) 4-PBA suppressed ERS-related apoptotic pathway (PERK-eIFa2-ATF4-CHOP), but did not suppress IH-induced unfold protein reaction (UPR). CONCLUSIONS 4-PBA could protect liver cells by suppressing IH-induced apoptosis mediated by ERS, but not by reducing the UPR.
Collapse
Affiliation(s)
- Liu Xin
- Geriatrics, Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China
| | - Wu Fan
- Geriatrics, Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China
| | - Du Tingting
- Geriatrics, Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China
| | - Sun Zuoming
- Beckman Research Institute of the City of Hope, Duarte, CA, USA
| | - Zhang Qiang
- Geriatrics, Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China.
| |
Collapse
|
|
25
|
Pilli VS, Datta A, Afreen S, Catalano D, Szabo G, Majumder R. Hypoxia downregulates protein S expression. Blood 2018; 132:452-455. [PMID: 29784640 PMCID: PMC6071559 DOI: 10.1182/blood-2018-04-841585] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Affiliation(s)
- Vijaya S Pilli
- Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, New Orleans, LA; and
| | - Arani Datta
- Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, New Orleans, LA; and
| | - Sadaf Afreen
- Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, New Orleans, LA; and
| | - Donna Catalano
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA
| | - Gyongyi Szabo
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA
| | - Rinku Majumder
- Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, New Orleans, LA; and
| |
Collapse
|
|
26
|
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.
Collapse
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.
| |
Collapse
|
|
27
|
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: 15] [Impact Index Per Article: 1.9] [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.
Collapse
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.
| |
Collapse
|
|
28
|
Luo B, Wang R, Li W, Yang T, Wang C, Lu H, Zhao A, Zhang J, Jia Z. Pharmacokinetic changes of norfloxacin based on expression of MRP2 after acute exposure to high altitude at 4300m. Biomed Pharmacother 2017; 89:1078-1085. [PMID: 28292016 DOI: 10.1016/j.biopha.2017.02.092] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Revised: 02/15/2017] [Accepted: 02/24/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300m. METHODS AND RESULTS The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, Ka and Cmax of norfloxacin were significantly reduced in high altitude group (p<0.05). However, the MRT, CL, t1/2 and Vd were significantly increased (p<0.05). CONCLUSIONS These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude.
Collapse
Affiliation(s)
- Bingfeng Luo
- Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China; School of Pharmacy, Lanzhou university, Lanzhou 730000, China
| | - Rong Wang
- Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China; School of Pharmacy, Lanzhou university, Lanzhou 730000, China.
| | - Wenbin Li
- Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China
| | - Tao Yang
- Department of Pharmacy, Gansu Provincial Maternity and Child Care Hospital, Lanzhou 730050, China
| | - Chang Wang
- Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China
| | - Hui Lu
- Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China
| | - Anpeng Zhao
- Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China
| | - Juanhong Zhang
- Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China; School of Pharmacy, Lanzhou university, Lanzhou 730000, China
| | - Zhengping Jia
- Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China.
| |
Collapse
|
|
29
|
Chen LD, Lin L, Zhang LJ, Zeng HX, Wu QY, Hu MF, Xie JJ, Liu JN. Effect of continuous positive airway pressure on liver enzymes in obstructive sleep apnea: A meta-analysis. CLINICAL RESPIRATORY JOURNAL 2016; 12:373-381. [PMID: 27614004 DOI: 10.1111/crj.12554] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 08/07/2016] [Accepted: 08/29/2016] [Indexed: 12/25/2022]
Abstract
BACKGROUND Previous studies have suggested that obstructive sleep apnea (OSA) was associated with nonalcoholic fatty liver disease (NAFLD). However, the impact of OSA treatment using continuous positive airway pressure (CPAP) on liver enzymes remained controversial. This meta-analysis was conducted to determine whether CPAP therapy could reduce liver enzyme levels. METHODS Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before December 2015. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of serum ALT and AST was extracted for analysis. A total of five studies with seven cohorts that included 192 patients were pooled into meta-analysis. RESULTS CPAP was associated with a statistically significant decrease on both ALT and AST levels in OSA patients (WMD = 8.036, 95% CI = 2.788-13.285, z = 3.00, P = .003 and WMD = 4.612, 95% CI = 0.817-8.407, z = 2.38, P = .017, respectively). Subgroup analyses indicated that CPAP therapy was more effective in OSA patients with treatment duration > 3 mo (WMD = 12.374, 95% CI = 2.727-22.020, z = 2.51, P = .012 for ALT and WMD = 7.576, 95% CI = 1.781-13.370, z =2.56, P = .010 for AST). CONCLUSION This meta-analysis suggested that CPAP was associated with a statistically significant decrease on liver enzymes in OSA patients. Further large-scale well-designed RCTs with long-term follow-up are required to clarify this issue.
Collapse
Affiliation(s)
- Li-Da Chen
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Li Lin
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Liang-Ji Zhang
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Hui-Xue Zeng
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Qi-Yin Wu
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Miao-Feng Hu
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Jian-Jun Xie
- Department of Radiation Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Jian-Nan Liu
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| |
Collapse
|
|
30
|
Liu C, Zhong R, Lou J, Pan A, Tang Y, Chang J, Ke J, Li J, Yuan J, Wang Y, Chen W, Guo H, Wei S, Liang Y, Zhang X, He M, Hu FB, Wu T, Yao P, Miao X. Nighttime sleep duration and risk of nonalcoholic fatty liver disease: the Dongfeng-Tongji prospective study. Ann Med 2016; 48:468-476. [PMID: 27327959 DOI: 10.1080/07853890.2016.1193787] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND To examine the association between self-reported nighttime sleep duration and nonalcoholic fatty liver disease (NAFLD) risk by comparing the incidence rates of NAFLD among healthy subjects with different sleep duration during the 5 years follow-up. METHODS 8965 eligible NAFLD-free subjects with a mean age of 61.6 years (males, 43.4%) from Dongfeng-Tongji cohort study at baseline were enrolled in the study. Logistic regression analysis was used to estimate the association between sleep duration and incident NAFLD with potential confounders adjusted. Sleep duration was categorized into five groups: <6 h, 6-7 h, 7-8 h, 8-9 h, ≥9 h. RESULT During the 5-years of follow-up, a total of 2,197 participants were newly diagnosed as NAFLD. Compared with those reported 7-8 h per day of nighttime sleep, the multivariable-adjusted odds ratio (95% confidence intervals) were 1.21 (1.07-1.38) for those who sleep 8-9 h/day, and 1.31 (1.13-1.52) for those who sleep over 9 h/day. However, no significant association was found with short nightly sleep duration (<7 h/day). CONCLUSION Long nighttime sleep duration was associated with a modestly increased risk of NAFLD in a middle-aged and elderly Chinese population. Key messages Long nighttime sleep duration was associated with a modestly increased risk of NAFLD in a middle-aged and elderly Chinese population. The effect of long nighttime sleep on the risk of incident NAFLD was attenuated greatly by body mass index (BMI) in men.
Collapse
Affiliation(s)
- Cheng Liu
- a Department of Epidemiology and Statistics, and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Rong Zhong
- a Department of Epidemiology and Statistics, and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Jiao Lou
- a Department of Epidemiology and Statistics, and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - An Pan
- a Department of Epidemiology and Statistics, and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Yuhan Tang
- b Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Jiang Chang
- c The Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Juntao Ke
- a Department of Epidemiology and Statistics, and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Jiaoyuan Li
- a Department of Epidemiology and Statistics, and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Jing Yuan
- d Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Youjie Wang
- c The Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Weihong Chen
- d Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Huan Guo
- d Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Sheng Wei
- a Department of Epidemiology and Statistics, and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Yuan Liang
- c The Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Xiaomin Zhang
- d Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Meian He
- d Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Frank B Hu
- e Department of Nutrition and Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston , USA
| | - Tangchun Wu
- d Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Ping Yao
- b Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| | - Xiaoping Miao
- a Department of Epidemiology and Statistics, and the Ministry of Education (MOE) Key Lab of Environment and Health, School of Public Health, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China
| |
Collapse
|
|
31
|
Aron-Wisnewsky J, Clement K, Pépin JL. Nonalcoholic fatty liver disease and obstructive sleep apnea. Metabolism 2016; 65:1124-35. [PMID: 27324067 DOI: 10.1016/j.metabol.2016.05.004] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Revised: 05/03/2016] [Accepted: 05/07/2016] [Indexed: 12/18/2022]
Abstract
Obstructive sleep apnea (OSA) and more importantly its hallmark, chronic intermittent hypoxia (CIH), are established factors in the pathogenesis and exacerbation of nonalcoholic fatty liver disease (NAFLD). This has been clearly demonstrated in rodent models exposed to intermittent hypoxia, and strong evidence now also exists in both paediatric and adult human populations. OSA and CIH induce insulin-resistance and dyslipidemia which are involved in NAFLD physiopathogenesis. CIH increases the expression of the hypoxia inducible transcription factor HIF1α and that of downstream genes involved in lipogenesis, thereby increasing β-oxidation and consequently exacerbating liver oxidative stress. OSA also disrupts the gut liver axis, increasing intestinal permeability and with a possible role of gut microbiota in the link between OSA and NAFLD. OSA patients should be screened for NAFLD and vice versa those with NAFLD for OSA. To date there is no evidence that treating OSA with continuous positive airway pressure (CPAP) will improve NAFLD but it might at least stabilize and slow its progression. Nevertheless, these multimorbid patients should be efficiently treated for all their metabolic co-morbidities and be encouraged to follow weight stabilization or weight loss programs and physical activity life style interventions.
Collapse
Affiliation(s)
- Judith Aron-Wisnewsky
- Institute of Cardiometabolism and Nutrition, ICAN, Assistance Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, UMR_S U1166, Nutriomics, 75013 Paris, France; INSERM, UMR_S U1166, Nutriomics, 75013 Paris, France.
| | - Karine Clement
- Institute of Cardiometabolism and Nutrition, ICAN, Assistance Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, UMR_S U1166, Nutriomics, 75013 Paris, France; INSERM, UMR_S U1166, Nutriomics, 75013 Paris, France
| | - Jean-Louis Pépin
- Institut National de la Santé et de la Recherche Médicale (INSERM), U 1042, HP2 Laboratory (Hypoxia: Pathophysiology), Grenoble Alpes Univ., Grenoble, F-38000, France;; Grenoble Alpes University Hospital, Pole Thorax et Vaisseaux, F-38000, France.
| |
Collapse
|
|
32
|
Chen X, Lin X, Chen LD, Lin QC, Chen GP, Yu YH, Huang JC, Zhao JM. Obstructive sleep apnea is associated with fatty liver index, the index of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2016; 28:650-655. [PMID: 26894633 DOI: 10.1097/meg.0000000000000598] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND OBJECTIVES The relationship between obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) is gaining increased attention. The aim of the present study was to examine the relationship of OSA with NAFLD defined by an elevated fatty liver index (FLI). MATERIALS AND METHODS A total of 319 consecutive patients who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for biological profile measurements, and demographic data were collected. Values of FLI were determined and assessed as predictors of the presence of NAFLD, as measured by ultrasound. The discriminative ability of FLI was estimated on the basis of the area under the receiver operator characteristic curve. RESULTS An FLI of 60 achieved the highest diagnostic accuracy and yielded an area under the receiver operator characteristic curve of 0.822 (95% confidence interval: 0.729-0.916) in the detection of NAFLD. Patients with an FLI of 60 or higher had a significantly lower lowest O2 saturation (73 vs. 83%, P<0.001), a lower mean nocturnal oxygen saturation (93 vs. 95%, P<0.001), a higher apnea-hypopnea index (39.7 vs. 18.4, P<0.001), a higher oxygen desaturation index (39 vs. 10.6, P<0.001), and a higher percentage of sleep time spent with SpO2 less than 90% (4.63 vs. 0.92%, P<0.001) compared with those with FLI less than 60. In multivariate analysis, the presence of OSA was independently associated with elevated FLI after adjusting for confounding factors (odds ratio: 5.141, 95% confidence interval: 1.414-18.696, P=0.013). CONCLUSION Our results suggest a positive association between the severity of OSA and NAFLD defined by an elevated FLI, which may serve as a good biomarker for detecting NAFLD in OSA patients.
Collapse
Affiliation(s)
- Xiao Chen
- aDepartment of Intensive Care Unit bLaboratory of Respiratory Disease of the Fujian Medical University, Department of Respiratory Medicine, Fujian Provincial Sleep-disordered Breathing Clinic Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou cDepartment of Respiratory Medicine, Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou dDepartment of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Paz Y Mar HL, Hazen SL, Tracy RP, Strohl KP, Auckley D, Bena J, Wang L, Walia HK, Patel SR, Mehra R. Effect of Continuous Positive Airway Pressure on Cardiovascular Biomarkers: The Sleep Apnea Stress Randomized Controlled Trial. Chest 2016; 150:80-90. [PMID: 26997243 DOI: 10.1016/j.chest.2016.03.002] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 02/26/2016] [Accepted: 03/01/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Although existing research highlights the relationship of OSA and cardiovascular disease, the effect of OSA treatment on cardiovascular biomarkers remains unclear. We evaluated the effect of OSA treatment on oxidative stress/inflammation measures. METHODS We conducted a parallel, randomized controlled trial in moderate to severe OSA (apnea-hypopnea index ≥ 15) patients to examine effects of 2-month CPAP vs sham-CPAP on the primary outcome of oxidative stress/inflammation (F2-isoprostanes: ng/mg) and myeloperoxidase: pmol/L) and secondary oxidative stress measures. Exploratory secondary analyses included vascular and systemic inflammation markers. Linear models adjusted for baseline values examined effect of CPAP on biomarker change (least squares means, 95% CI) including secondary stratified analyses examining CPAP adherence and degree of hypoxia. RESULTS Of 153 participants, 76 were randomized to CPAP and 77 to sham-CPAP. In an intent-to-treat analyses, no significant change was observed in the sham and CPAP groups respectively: F2-isoprostanes (-0.02 [-0.12 to 0.10] vs -0.08 [-0.18 to 0.03]) or myeloperoxidase (-3.33 [-17.02 to 10.37] vs -5.15 [-18.65 to 8.35]), nor other oxidative markers; findings that persisted in analyses stratified by adherence and hypoxia. Exploratory analyses revealed percentage reduction of soluble IL-6 receptor (ng/mL) levels (-0.04 [-0.08 to -0.01] vs 0.02 [-0.02 to 0.06], P = .019) and augmentation index (%) (-6.49 [-9.32 to -3.65] vs 0.44 [-2.22 to 3.10], P < .001) with CPAP compared with sham, respectively. CONCLUSIONS In moderate to severe OSA, 2-month CPAP vs sham did not reduce oxidative stress despite consideration of a broad range of measures, positive airway pressure adherence, and hypoxia burden. These findings suggest that nonoxidative stress pathways primarily modulate OSA-related cardiovascular consequences. TRIAL REGISTRATION ClinicalTrials.govNCT00607893.
Collapse
Affiliation(s)
- Hugo L Paz Y Mar
- Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH
| | - Stanley L Hazen
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | - Russell P Tracy
- Departments of Biochemistry and Pathology, University of Vermont, Burlington, VT
| | - Kingman P Strohl
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH
| | - Dennis Auckley
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, MetroHealth Medical Center, Cleveland, OH
| | - James Bena
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | - Lu Wang
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | - Harneet K Walia
- Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH
| | - Sanjay R Patel
- Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Reena Mehra
- Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH; Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
| |
Collapse
|
|
34
|
Wang S, Song J, Yang Y, Zhang Y, Wang H, Ma J. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT. PLoS One 2015; 10:e0145944. [PMID: 26717317 PMCID: PMC4696784 DOI: 10.1371/journal.pone.0145944] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 12/10/2015] [Indexed: 12/18/2022] Open
Abstract
Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18–1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7–17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom’s MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P<0.05), and found positive associations between methylation and alanine aminotransferase (ALT) levels adjusted by gender, age and BMI at the position 46801699 (r = 0.226, P = 0.007). These results suggest that HIF3A DNA methylation is associated with childhood obesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD).
Collapse
Affiliation(s)
- Shuo Wang
- Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China
| | - Jieyun Song
- Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China
| | - Yide Yang
- Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China
| | - Yining Zhang
- Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China
| | - Haijun Wang
- Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China
| | - Jun Ma
- Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China
| |
Collapse
|
|
35
|
Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease. PLoS One 2015; 10:e0142210. [PMID: 26672595 PMCID: PMC4682677 DOI: 10.1371/journal.pone.0142210] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 10/19/2015] [Indexed: 12/12/2022] Open
Abstract
Background/Aims We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. Methods Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defined as a focal thickening >1.3 mm. Results Prevalence of high OSA risk was similar in patients refusing or accepting PG (76% vs 68%, p = 0.17). Among those accepting PG, overall OSA prevalence was significantly higher in patients with F2-F4 fibrosis compared to those without (72% vs 44%; p = 0.04). Significant fibrosis was independently associated with mean nocturnal oxygen saturation (SaO2)<95% (OR 3.21, 95%C.I. 1.02–7.34; p = 0.04). Prevalence of OSA tended to be higher in patients with, than in those without, carotid plaques (64% vs 40%; p = 0.08). Carotid plaques were independently associated with %time at SaO2<90% >1 (OR 6.30, 95%C.I. 1.02–12.3; p = 0.01). Conclusions In NAFLD patients with chronically elevated ALT at low prevalence of morbid obesity, OSA was highly prevalent and indexes of SaO2 resulted independently associated with severity of liver fibrosis and carotid atherosclerosis. These data suggest to consider sleep disordered breathing as a potential additional therapeutic target in severe NAFLD patients.
Collapse
|
|
36
|
Cakmak E, Duksal F, Altinkaya E, Acibucu F, Dogan OT, Yonem O, Yilmaz A. Association Between the Severity of Nocturnal Hypoxia in Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Damage. HEPATITIS MONTHLY 2015; 15:e32655. [PMID: 26834793 PMCID: PMC4719120 DOI: 10.5812/hepatmon.32655] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/23/2015] [Revised: 09/20/2015] [Accepted: 09/22/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Obstructive sleep apnea (OSA) is a major disease that can cause significant mortality and morbidity. Chronic intermittent hypoxia is a potential causal factor in the progression from fatty liver to nonalcoholic steatohepatitis. OBJECTIVES This study evaluated the association between the degree of liver steatosis and severity of nocturnal hypoxia. PATIENTS AND METHODS In this study, between December 2011 and December 2013, patients with ultrasound-diagnosed NAFLD evaluated by standart polysomnography were subsequentally recorded. Patients with alcohol use, viral hepatitis and other chronic liver diseases were excluded. We analyzed polysomnographic parameters, steatosis level and severity of obstructive sleep apnea (OSA) in consideration of body mass index (BMI), biochemical tests and ultrasonographic liver data of 137 subjects. Patients with sleep apnea and AHI scores of < 5, 5 - 14, 15 - 29 and ≥30 are categorized as control, mild, moderate and severe, respectively. RESULTS One hundred and thirty-seven patients (76 women, 61 men) with a mean age of 55.75 ± 10.13 years who underwent polysomnography were included in the study. Of 118 patients diagnosed with OSA, 19 (16.1%) had mild OSA, 39 (33.1%) moderate OSA and 60 (50.8%) severe OSA. Nineteen cases formed the control group. Apnea/hypopnea index and oxygen desaturation index (ODI) values were significantly higher in moderate and severe non-alcoholic fatty liver disease (NAFLD) compared to the non-NAFLD group. Mean nocturnal SpO2 values were significantly lower in mild NAFLD and severe NAFLD compared to the non-NAFLD group. Lowest O2 saturation (LaSO2) was found low in mild, moderate and severe NAFLD compared to the non-NAFLD group in a statistically significant manner. CONCLUSIONS We assessed polysomnographic parameters of AHI, ODI, LaSO2 and mean nocturnal SpO2 levels, which are especially important in the association between NAFLD and OSAS. We think that it is necessary to be attentive regarding NAFLD development and progression in patients with OSA whose nocturnal hypoxia is severe.
Collapse
Affiliation(s)
- Erol Cakmak
- Department of Gastroenterology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
- Corresponding Author: Erol Cakmak, Department of Gastroenterology, Cumhuriyet University Faculty of Medicine, P. O. Box: 58140, Sivas, Turkey. Tel: +90-3464444458, Fax: +90-3462239530, E-mail:
| | - Faysal Duksal
- Department of Chest Diseases, Sivas Numune Hospital, Sivas, Turkey
| | - Engin Altinkaya
- Department of Gastroenterology, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Fettah Acibucu
- Department of Endocrinology, Sivas Numune Hospital, Sivas, Turkey
| | - Omer Tamer Dogan
- Department of Chest Diseases, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Ozlem Yonem
- Department of Gastroenterology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Abdulkerim Yilmaz
- Department of Gastroenterology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| |
Collapse
|
|
37
|
Corey KE, Misdraji J, Gelrud L, King LY, Zheng H, Malhotra A, Chung RT. Obstructive Sleep Apnea Is Associated with Nonalcoholic Steatohepatitis and Advanced Liver Histology. Dig Dis Sci 2015; 60:2523-8. [PMID: 25840922 PMCID: PMC4499481 DOI: 10.1007/s10620-015-3650-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Accepted: 03/26/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are growing in prevalence in the USA. Existing data on the relationship between OSA and NAFLD are conflicting and limited by the use of various histologic definitions of nonalcoholic steatohepatitis (NASH). Using a robust definition of NASH in a large, well-characterized cohort, we sought to evaluate whether OSA was associated with NASH and advanced fibrosis. METHODS Two hundred and thirteen subjects undergoing weight loss surgery were queried for OSA and then underwent liver biopsy. NASH was defined, as recommended by the American Association for the Study of Liver Disease, by the presence of all of the following: >5 % macrovesicular steatosis, lobular inflammation, and hepatocyte ballooning. NAFLD activity score (NAS) was also determined for each subject. RESULTS Subjects with OSA had significantly higher alanine and aspartate aminotransferase levels than subjects without OSA (ALT 54.1 vs. 37.7 U/L, P = 0.0007; AST 31.7 vs. 20.5 U/L, P = 0.0007). OSA was associated with the presence of NASH, and this remained significant after adjusting for age, gender, race, and diabetes mellitus (P = 0.03 OR 2.01; 95 %, 1.05-3.87). Steatosis grade, lobular inflammation grade, NAS score, and fibrosis stage were all significantly associated with the presence of OSA and remained so after adjustment. CONCLUSIONS OSA is associated with elevated aminotransferase levels, the presence of NASH, and advanced NASH histology. Further studies are needed to evaluate the impact of OSA treatment on NASH.
Collapse
Affiliation(s)
- Kathleen E Corey
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA
,Harvard Medical School, Boston, MA
| | - Joseph Misdraji
- Department of Pathology, Massachusetts General Hospital, Boston, MA
,Harvard Medical School, Boston, MA
| | - Lou Gelrud
- Department of Internal Medicine, Bon Secours Richmond Health System, Richmond, VA
| | - Lindsay Y. King
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA
| | - Hui Zheng
- MGH Biostatistics Center, Massachusetts General Hospital, Boston, MA
,Harvard Medical School, Boston, MA
| | - Atul Malhotra
- Department of Pulmonary and Critical Care Medicine, University of California San Diego, San Diego, CA
| | - Raymond T Chung
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA
,Harvard Medical School, Boston, MA
| |
Collapse
|
|
38
|
Qi JC, Huang JC, Lin QC, Zhao JM, Lin X, Chen LD, Huang JF, Chen X. Relationship between obstructive sleep apnea and nonalcoholic fatty liver disease in nonobese adults. Sleep Breath 2015; 20:529-35. [PMID: 26174847 DOI: 10.1007/s11325-015-1232-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Accepted: 07/03/2015] [Indexed: 12/15/2022]
Abstract
PURPOSE Obstructive sleep apnea (OSA) is closely related to nonalcoholic fatty liver disease (NAFLD), though the mechanism is not conclusive as obesity is a confounder. The objective of this observational study was to investigate the correlation between these disorders in nonobese subjects. METHODS We consecutively enrolled nonobese individuals undergoing polysomnography and abdominal ultrasonography and analyzed differences in NAFLD patients grouped by the apnea-hypopnea index (AHI) and in OSA patients according to the presence or absence of NAFLD. Multivariate regression analysis was used to evaluate the independent risks of NAFLD in OSA patients. RESULTS A total of 175 participants were included. The 106 ultrasound-diagnosed NAFLD patients were classified into four groups by AHI. There were no significant differences in triglycerides (TG), serum aminotransferase levels of alanine aminotransferase and aspartate aminotransferase, high-sensitivity C-reactive protein, and homeostasis model assessment of insulin resistance (HOMA-IR) with worsening OSA. In both OSA patients with NAFLD and those without NAFLD, body mass index (BMI), the lowest oxygen saturation (LaSO2), HOMA-IR, and TG were significantly associated. Additionally, BMI, LaSO2, and TG independently predicted the development of NAFLD after adjustments (odds ratio [OR] = 1.562, p = 0.003; OR = 0.960, p = 0.03; OR = 3.410, p < 0.001, respectively). CONCLUSIONS In nonobese subjects, OSA itself does not appear to induce significant changes in liver enzymes. With reference to lipid metabolism, weight control and OSA-related hypoxemia are key factors in reducing the risk of NAFLD in OSA patients. Additional large-scale, prospective studies are warranted to investigate the impact of OSA on liver injury in nonobese adults.
Collapse
Affiliation(s)
- Jia-Chao Qi
- Fujian Provincial Sleep-Disordered Breathing Clinic Center, Laboratory of Respiratory Disease of the Fujian Medical University, Department of Respiratory Medicine, the First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Rd., Taijiang, Fuzhou, 350005, Fujian Province, People's Republic of China
| | - Jian-Chai Huang
- Fujian Provincial Sleep-Disordered Breathing Clinic Center, Laboratory of Respiratory Disease of the Fujian Medical University, Department of Respiratory Medicine, the First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Rd., Taijiang, Fuzhou, 350005, Fujian Province, People's Republic of China
| | - Qi-Chang Lin
- Fujian Provincial Sleep-Disordered Breathing Clinic Center, Laboratory of Respiratory Disease of the Fujian Medical University, Department of Respiratory Medicine, the First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Rd., Taijiang, Fuzhou, 350005, Fujian Province, People's Republic of China.
| | - Jian-Ming Zhao
- Fujian Provincial Sleep-Disordered Breathing Clinic Center, Laboratory of Respiratory Disease of the Fujian Medical University, Department of Respiratory Medicine, the First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Rd., Taijiang, Fuzhou, 350005, Fujian Province, People's Republic of China
| | - Xin Lin
- Fujian Provincial Sleep-Disordered Breathing Clinic Center, Laboratory of Respiratory Disease of the Fujian Medical University, Department of Respiratory Medicine, the First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Rd., Taijiang, Fuzhou, 350005, Fujian Province, People's Republic of China
| | - Li-Da Chen
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No. 59, West Shengli Rd., Xiangcheng, Zhangzhou, 363000, Fujian Province, People's Republic of China
| | - Jie-Feng Huang
- Fujian Provincial Sleep-Disordered Breathing Clinic Center, Laboratory of Respiratory Disease of the Fujian Medical University, Department of Respiratory Medicine, the First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Rd., Taijiang, Fuzhou, 350005, Fujian Province, People's Republic of China
| | - Xiao Chen
- Fujian Provincial Sleep-Disordered Breathing Clinic Center, Laboratory of Respiratory Disease of the Fujian Medical University, Department of Respiratory Medicine, the First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Rd., Taijiang, Fuzhou, 350005, Fujian Province, People's Republic of China
| |
Collapse
|
|
39
|
Multiscale Entropy Analysis of Heart Rate Variability for Assessing the Severity of Sleep Disordered Breathing. ENTROPY 2015. [DOI: 10.3390/e17010231] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
|