Liver Steatosis and Fibrosis in OSA patients After Long-term CPAP Treatment: A Preliminary Ultrasound Study

Buttacavoli, Maria; Gruttad'Auria, Claudia I.; Olivo, Mirko; Virdone, Roberto; Castrogiovanni, Alessandra; Mazzuca, Emilia; Marotta, A; Marrone, Oreste; Madonia, Salvatore; Bonsignore, Maria R.

doi:10.1016/j.ultrasmedbio.2015.08.009

Cited by 24 publications

(14 citation statements)

References 23 publications

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“…Insets are adapted with permission from References 13 and 68, as well as our unpublished data. cohorts (87,88). Though discouraging, these studies to date have been limited either by small cohorts studied or by limited time on CPAP.…”

Section: Osa Hypoxia and Hepatic Steatosismentioning

confidence: 99%

“…A few studies have examined the prevalence of OSA in patients with NAFLD and liver fibrosis (94,95), but these studies are lacking either in sample size or in definitive OSA diagnosis. In general, results of CPAP trials that have examined liver fibrosis as an outcome in subjects with OSA and NAFLD have been negative (87,88), but studies of surrogates of NASH progression such as aminotransferase concentrations have appeared more promising. Interestingly, despite mixed results in humans, the available data do suggest that rodents exposed to IH develop liver fibrosis, oxidative damage, and hepatic inflammatory injury, and when exposed to IH plus another hepatic insult (e.g., acetaminophen), they may also exhibit marked hepatocellular inflammation and necrosis (96)(97)(98).…”

Section: Osa Hypoxia and Hepatic Inflammation And Fibrosis In Nafldmentioning

confidence: 99%

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Obstructive Sleep Apnea, Hypoxia, and Nonalcoholic Fatty Liver Disease

Mesarwi

Loomba

Malhotra

2019

Am J Respir Crit Care Med

180

121

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Recent studies have demonstrated that obstructive sleep apnea (OSA) is associated with the development and evolution of nonalcoholic fatty liver disease (NAFLD), independent of obesity or other shared risk factors. Like OSA, NAFLD is a prevalent disorder associated with major adverse health outcomes: Patients with NAFLD may develop cirrhosis, liver failure, and hepatocellular carcinoma. One major finding that has emerged from these studies is that the OSA-NAFLD association is related to the degree of nocturnal hypoxemia in OSA. Animal models have therefore largely focused on intermittent hypoxia, a key manifestation of OSA, to shed light on the mechanisms by which OSA may give rise to the complex metabolic disturbances that are seen in NAFLD. Intermittent hypoxia leads to tissue hypoxia and can result in oxidative stress, mitochondrial dysfunction, inflammation, and overactivation of the sympathetic nervous system, among many other maladaptive effects. In such models, intermittent hypoxia has been shown to cause insulin resistance, dysfunction of key steps in hepatic lipid metabolism, atherosclerosis, and hepatic steatosis and fibrosis, each of which is pertinent to the development and/or progression of NAFLD. However, many intriguing questions remain unanswered: Principally, how aggressively should the clinician screen for NAFLD in patients with OSA, and vice versa? In this review, we attempt to apply the best evidence from animal and human studies to highlight the relationship between these two disorders and to advocate for further trials aimed at defining these relationships more precisely.

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Section: Osa Hypoxia and Hepatic Steatosismentioning

confidence: 99%

Section: Osa Hypoxia and Hepatic Inflammation And Fibrosis In Nafldmentioning

confidence: 99%

Obstructive Sleep Apnea, Hypoxia, and Nonalcoholic Fatty Liver Disease

Mesarwi

Loomba

Malhotra

2019

Am J Respir Crit Care Med

180

121

View full text Add to dashboard Cite

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“…Another randomized study that evaluated the effect of CPAP treatment on liver fibrosis, using the FibroMax score (non-invasive testing called biopredictive tests that work by using an algorithm based on the patients’ sex, age, weight, height and specific blood biomarkers) did not demonstrate any impact on reducing fibrosis; even though, it had more than 100 patients [ 16 ]. Contrary to the conclusions drawn from these randomized controlled trials, many observational and prospective cohort studies have associated adherence to CPAP therapy with improvement in liver enzymes and radiological steatosis [ 76 - 78 ]. Kim et al also concluded that there was a potential for reduction in liver fibrosis [ 79 ].…”

Section: Discussionmentioning

confidence: 99%

A Case of Concomitant Obstructive Sleep Apnea and Non-Alcoholic Steatohepatitis Treated With CPAP Therapy

Bajantri

Lvovsky

2018

Gastroenterol Res

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Obstructive sleep apnea syndrome is a disorder of sleep breathing that is a result of recurrent and intermittent hypoxia during sleep induced by the repeated partial or complete collapse of the upper airway, eventually causing chronic intermittent hypoxia. Non-alcoholic fatty liver disease is divided into non-alcoholic fatty liver and non-alcoholic steatohepatitis. Animal and human studies showed that obesity is associated with chronic liver hypoxia, even in the presence of systemic normoxia causing inflammation and release of cytokines. A “two-hit” model has been proposed. The first hit is characterized by insulin resistance and excess hepatic lipid accumulation secondary to abnormal fatty acid metabolism. Oxidative stress and inflammation are thought to comprise the second hit. Gold standard for the diagnosis of non-alcoholic steatohepatitis is a liver biopsy. Many clinical scores and non-invasive tools are used for the diagnosis of non-alcoholic steatohepatitis. Conservative management with lifestyle modifications including diet, exercise and weight loss remains the therapy of choice today. We present a case report of a 39-year-old man who was diagnosed with concomitant non-alcoholic steatohepatitis and severe obstructive sleep apnea. He was started treatment with continuous positive airway pressure and demonstrated excellent adherence to therapy for 6 years, with concomitant obstructive sleep apnea and non-alcoholic steatohepatitis which reversed with prolonged optimal continuous positive airway pressure therapy. Physical examination remained unremarkable except for morbid obesity. His abdominal girth, as well as body mass index, remained unchanged. After 6 years of optimal continuous positive airway pressure therapy, liver enzymes and relevant lipid panel normalized, suggesting reversal of non-alcoholic steatohepatitis.

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“…The identification of OSA in patients with NAFLD could be followed by OSA treatment, with benefits on metabolic and perhaps liver alterations. A recent longitudinal study from our group suggested that OSA treatment by continuous positive airway pressure might be associated with decreased liver steatosis [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

et al. 2015

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Background/AimsWe 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.MethodsConsecutive 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.ResultsPrevalence 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).ConclusionsIn 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.

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Liver Steatosis and Fibrosis in OSA patients After Long-term CPAP Treatment: A Preliminary Ultrasound Study

Cited by 24 publications

References 23 publications

Obstructive Sleep Apnea, Hypoxia, and Nonalcoholic Fatty Liver Disease

Obstructive Sleep Apnea, Hypoxia, and Nonalcoholic Fatty Liver Disease

A Case of Concomitant Obstructive Sleep Apnea and Non-Alcoholic Steatohepatitis Treated With CPAP Therapy

Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

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