Published online May 28, 2020. doi: 10.3748/wjg.v26.i20.2669
Peer-review started: January 27, 2020
First decision: March 6, 2020
Revised: March 26, 2020
Accepted: May 15, 2020
Article in press: May 15, 2020
Published online: May 28, 2020
The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is multifactorial and is commonly described as a two-hit model. The first hit is characterized by an increased triglyceride accumulation in the hepatocytes due to obesity and insulin resistance. The second hit is characterized by lipotoxic metabolite production, liver inflammation and steatosis progression due to oxidative stress, lipid peroxidation, mitochondrial dysfunction and some gene polymorphisms. In obstructive sleep apnea (OSA) hypoxic environment, there is an increased adipose tissue lipolysis, oxidative stress, inflammation and liver fibrosis. OSA is a well-established independent factor of insulin resistance, which may predispose to the development and the progression of liver steatosis. However, to clarify the effects of OSA on the development and progression of NAFLD is challenging due to the several comorbidities which common coexist and are independently associated with systemic inflammation.
NAFLD is an emerging liver disease. The increased mortality of patients with NAFLD is primarily a result of cardiovascular diseases and, to a lesser extent, to liver related diseases. OSA is still underdiagnosed; its prevalence is estimated to be 4% in the general population increasing up to 40% in some disease-specific populations, such as in patients suffering from cardiovascular disease or metabolic syndrome. Probably the atypical presentation, the lack of data on the criteria for identifying OSA and the lack of awareness of this entity among clinicians are important reasons. Since OSA may be linked with the pathogenesis and the severity of NAFLD, it is very important to early and better diagnose and treat OSA in NAFLD patients, in which numerous cardiovascular and metabolic comorbidities often coexist.
The aim of this systematic review is to provide a more comprehensive overview of the association between NAFLD and OSA considering also the efficacy of the gold standard treatment for the clinical management of OSA, the continuous positive airway pressure (CPAP) treatment.
A PubMed search limited to the last 5 years was conducted using the terms “non-alcoholic fatty liver disease AND (obstructive sleep apnea OR obstructive sleep disorders OR sleep apnea)”. We did not consider animal and child studies, case reports, commentaries, letters, editorials and meeting abstracts.
Initially, a total of 132 articles were retrieved on PubMed search and 77 in the last 5 years. After removal of irrelevant studies, 13 articles were included in the qualitative analysis. 2753 participants with a mean age between 42 and 58 years were included across all the studies. The proportion of males ranged from 21% to 87.9% and the mean body mass index ranged from 24.0 to 49.9 kg/m2. The results of this systematic review showed an increased prevalence of NAFLD in patients with OSA, even in the absence of coexisting comorbidities such as obesity or metabolic syndrome. Furthermore, the severity of NAFLD is associated with the increase in OSA severity. Effective CPAP treatment may stabilize or slow NAFLD progression with benefits on metabolic and cardiovascular functions.
NAFLD seems to be closely associated with OSA even in the absence of coexisting comorbidities such as obesity or MetS. Hypoxia should be considered to have a key role in the pathogenesis of NAFLD. Therefore, all OSA patients, even relatively lean, should be referred to hepatologists for specific management and all NAFLD patients, even if asymptomatic, should be screened for OSA. Effective CPAP treatment, although not always decisive, may stabilize or slow NAFLD progression with benefits on metabolic and cardiovascular functions. The systematic use of polysomnography in NAFLD patients, although asymptomatic, will help clinicians to early diagnose OSA and better treat it before the development of potentially life threatening systemic dysfunctions.
The association between NAFLD and OSA has been reviewed. A strong collaboration between gastroenterology and sleep medicine will have a key role in the management of these two conditions. Future research is needed to validate the efficacy of CPAP treatment on liver steatosis with longer longitudinal studies.