Elsevier

Hepatology Research

Volume 33, Issue 2, October 2005, Pages 100-104
Hepatology Research

Effects of obstructive sleep apnea syndrome on hepatic steatosis and nonalcoholic steatohepatitis

https://doi.org/10.1016/j.hepres.2005.09.014Get rights and content

Abstract

Hepatic steatosis occasionally progresses to nonalcoholic steatohepatitis. This study was designed to examine whether non-obese patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) were prone to develop hepatic steatosis and whether repeated hypoxemia contributed to the progression of steatohepatitis.

This study included 83 OSAHS patients and 41 age-, body mass index (BMI)- and gender-matched non-OSAHS patients diagnosed by polysomnography. Hepatic steatosis was defined by a liver/spleen ratio <0.9 on abdominal computerized tomography, and latent steatohepatitis was evaluated based on serum levels of type III procollagen (P-III-P).

Visceral fat (V-fat) accumulated much more in OSAHS patients. Liver/spleen ratios in OSAHS patients correlated negatively with BMI and, especially, with the amount of visceral fat. Serum levels of P-III-P in OSAHS patients correlated negatively with the average of oxygen saturation during sleep, and positively with BMI, the apnea-hypopnea index (AHI) and the amount of V-fat. Multiple regression analysis showed that average SaO2 was the only explanatory variable for P-III-P values, but AHI, BMI and V-fat was not.

These observations confirmed that non-obese patients with OSAHS are at a risk for visceral obesity, and suggested that oxygen desaturation during sleep is a risk for developing latent steatohepatitis, especially in patients with substantial hepatic steatosis.

Introduction

Obstructive sleep apnea-hypopnea syndrome (OSAHS) attracts much attention because of emerging data on important cardiovascular sequelae [1], [2]. Obesity, male sex, and older age are recognized to be risk factors for OSAHS and obesity is known to play a major role, because many patients with this disorder are obese and obesity is the only reversible risk factor of importance [3]. In addition, obstructive sleep apnea has been shown to be associated with visceral fat accumulation [4] and thereby the risk of obesity-related disorders. Simultaneous presence of obesity and OSAHS could increase cardiovascular complications.

Obesity is also recognized as a risk factor for developing hepatic steatosis [5] and hepatic steatosis, irrespective of its etiology, could be the first step in the pathogenesis of steatohepatitis [6]. Alcohol is a well-established cause of steatohepatitis, but steatohepatitis with necroinflammation, liver fibrosis and even cirrhosis could also be induced by nonalcoholic factors (nonalcoholic steatohepatitis, NASH) [7]. The “two-hit theory” is proposed to explain the development of NASH, in which a “second hit” capable of inducing hepatocytes necrosis, inflammation, and fibrosis is indispensable in addition to simple steatosis [8].

A case of NASH with Pickwickian syndrome, also known as obesity-hypoventilation syndrome, was reported [9]. Hypoxemia associated with that syndrome, which could accelerate hepatocytes destruction, was proposed as a factor contributing to the progression of liver fibrosis since hepatocytes are very susceptible to hypoxia [10]. One of the features of OSAHS in Japan is that about 30% of the patients are non-obese [3], and the pathophysiological characteristics of this subgroup of patients have not been defined. In addition, in non-obese patients OSAHS may represent an initial stage of hepatic steatosis. Therefore, in this study, the association between non-obese (body mass index (BMI)  30) OSAHS and visceral fat accumulation, hepatic steatosis and steatohepatitis were investigated.

Section snippets

Patients

The study population consisted of 83 non-obese (BMI  30) patients with OSAHS and 41 without OSAHS. No statistically significant difference was observed between these two groups regarding age, body mass index or gender. OSAHS was diagnosed based on the findings of polysomnography (PSG). Individuals with excessive alcohol consumption (>20 g/day) and those with hepatitis virus B and/or C were excluded by systematic history taking and blood tests, since this study was designed to examine the

Patients with OSAHS versus those without OSAHS

Patients with OSAHS and those without OSAHS showed comparable data in area of S-fat, L/S ratio, serum AST and ALT, whereas the area of V-fat and V/S ratio in addition to serum levels of TG and FPG were significantly higher in patients with OSAHS (Table 1). These results confirmed the previous observation that OSAHS was associated with V-fat accumulation [4].

Factors associated with hepatic steatosis in OSAHS patients

Obese OSAHS patients were excluded from this study to match BMI between patients with OSAHS and those without OSAHS, but other factors not

Discussion

Non-alcoholic fatty liver disease has only recently become widely recognized as a source of liver injury [17]. It is often diagnosed on a presumptive basis when liver enzyme elevations are noted in overweight or obese individuals without any known identifiable etiology for liver disease, or when imaging studies suggest hepatic steatosis. For this reason, the term includes a spectrum of disorders ranging from simple fatty liver to NASH. Indeed, NASH is the most progressive form of this syndrome

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      Previous studies have postulated a relationship between OSA and liver disease since 2005. A study of 83 people with OSA and matched controls suggested a relationship between OSA and the progression of steatosis to steatohepatitis [29]. In a larger study of 218 people with OSA, severe OSA (defined as >50 apneic/hypopneic episodes/h [AHI]) was associated with increased liver enzymes (OR 5.9, p < 0.02).

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