Roles of olive oil and physical exercise in non-alcoholic fatty liver disease after ultrasound-based evaluation

Abstract

Non-alcoholic fatty liver disease (NAFLD) without special drugs shows symptoms of liver fat accumulation and steatosis in patients without alcohol intake. Ultrasound evaluation is a critical method in the early diagnosis of NAFLD stages as well as image processing and should be encouraged. Olive oil is an important component of the Mediterranean diet and has a beneficial role in the prevention of NAFLD progression. Physical activity and exercise can have anti-oxidant and anti-inflammatory effects to reduce liver fat and body weight via regulation of mitochondrial capacity in the development of NAFLD. Both the Mediterranean diet and physical exercise should be combined to achieve the ideal fat content reduction and weight loss in patients with NAFLD.

Key Words: Olive oil; Non-alcoholic fatty liver disease; Mediterranean diet; Physical activity and exercise; Ultrasound analysis

Core Tip: This article is a response to the published paper by Zhu based on the track article quality report from an editorial board member/peer-reviewer. Olive oil in the Mediterranean diet was proposed to have an effective role in preventing non-alcoholic fatty liver disease progression. In addition, physical activity and exercise displayed a critical role in the prevention of non-alcoholic fatty liver disease development.

TO THE EDITOR

The Mediterranean diet in various civilizations has been associated with longevity and low cardiovascular risk and promotes health benefits in humans[1]. The geographical location of specific countries/areas as well as latitude and climate appear to have special behavioral and social features on the lifestyle of those consuming the Mediterranean diet[2]. The Mediterranean diet containing polyunsaturated fats, polyphenols, vitamins and carotenoids has anti-oxidant and anti-inflammatory effects and can alter chronic diseases such as non-alcoholic fatty liver disease (NAFLD) in terms of inflammatory progression and oxidative stress[3]. To demonstrate the corresponding components in the Mediterranean diet which affect the development of NAFLD, this article explores the topics outlined in a previous publication which require further study[4].

ROLES OF OLIVE OIL AND PHYSICAL EXERCISE IN NAFLD

NAFLD including non-alcoholic fatty liver without inflammation and non-alcoholic steatohepatitis (NASH) with inflammation can display a wide range of clinical presentations highly related to cardiovascular events[5]. NASH can easily develop into serious conditions such as hepatic fibrosis, cirrhosis and hepatocellular carcinoma, hence it is important to determine the stage of NASH during diagnosis[6]. Recently, it was reported that metabolic associated fatty liver disease had a similar presentation to NAFLD but was found in older patients with higher body mass index and metabolic syndromes[7]. Liver biopsy is used to evaluate the status of NAFLD in the clinic and is the gold standard in spite of its invasiveness and high cost for patients[8]. Ultrasound is now becoming the most appropriate assessment due to its availability and rapid detection in the primary diagnosis of NAFLD[9]. It was reported that early diagnosis and continuous monitoring are important in improving the outcomes of patients with NAFLD, while lifestyle management including diet adherence and exercise are encouraged in the early stage[10]. Although the convenience and low cost of conventional ultrasound are important factors in the clinical diagnosis of NAFLD, its sensitivity and specificity are unsatisfactory. An improved method of quantitative ultrasound using the ultrasound-estimated fat fraction parameter can determine steatosis in the diagnosis of NAFLD by magnetic resonance imaging proton density fat fraction with good accuracy[11]. Based on a meta-analysis study, both shear wave elastography and magnetic resonance elastography showed good diagnostic accuracy, sensitivity, and specificity for patients with NAFLD[12]. Currently, deep learning technique can be beneficial in screening ultrasound images for clinical diagnosis[13]. In this letter, we provide a method using Gaussian noise and Wiener denoise filters to determine the changes in mean squared error (MSE) and peak signal-to-noise ratio (PSNR) to identify NAFLD stages in patients. The associated ultrasound images of distinct stages of NAFLD were obtained from references[10] and transformed into gray images for subsequent analysis using MATLAB software in our computer platform. The filter for Gaussian noise used the following formula (1) from reference[14]:

where defined pixels of the gray image and σ was the standard deviation. The filter for Wiener denoise was then used to treat the above image with the following formula (2) based on reference[15]:

where F (×) was the Fourier transform and H (×) indicated the blurring function. The values of MSE and PSNR in the ultrasound images were obtained after the Gaussian noise and/or Wiener denoise filters were applied to perform the image processing effects using the following formula (3) and (4) in reference[16]:

where and were used to represent different filter treatments under the gray image and M and N were defined image of size M × N.

As shown in Figure 1, ultrasound images under gray level A, D, G, and J were obtained from reference[10], with primary images representing four different statuses of liver in the development of NAFLD. To overcome the background of these primary ultrasound images, image processing was used in our computer resources as described above. In Figure 1, Gaussian noise and Wiener denoise filters were applied to treat the gray ultrasound images of distinct stages in the development of NAFLD. To quantify the effects of the Gaussian noise and Wiener denoise filters under gray ultrasound images, the parameters MSE and PSNR were applied to display these changes in the different stages of NAFLD progression and are shown in Table 1. The results showed that Gaussian noise and Wiener denoise filters can decrease the MSE and increase the PSNR in ultrasound images of different stages of NAFLD compared to the gray level of corresponding images. And the Wiener denoise filter partly recovered the MSE and reduced the PSNR of ultrasound images at distinct stages in the development of NAFLD compared with the Gaussian noise filter.

Figure 1 Ultrasound of different stages of non-alcoholic fatty liver disease accompanied by image noise addition and reduction. A: Gray image of normal liver; B: Gaussian noise on A under gray level; C: Wiener denoise on B; D: Gray image of mild non-alcoholic fatty liver disease (NAFLD); E: Gaussian noise on D under gray level; F: Wiener denoise on E; G: Gray image of moderate NAFLD; H: Gaussian noise on G under gray level; I: Wiener denoise on H; J: Gray image of severe NAFLD; K: Gaussian noise on J under gray level; L: Wiener denoise on K.

Table 1 Values of mean squared error and peak signal-to-noise ratio in ultrasound images with Gaussian noise and Wiener denoise filters in different stages of non-alcoholic fatty liver disease.

NAFLD stages	Normal	Mild	Moderate	Severe
MSE values in ultrasound image under gray level	6.225 × 103	3.998 × 103	3.232 × 103	5.140 × 103
PSNR values in ultrasound image under gray level	10.189	12.112	13.036	11.021
MSE values in ultrasound image with Gaussian noise under gray level	15.255	1.698	10.128	11.063
PSNR values in ultrasound image with Gaussian noise under gray level	36.297	45.833	38.075	37.692
MSE values in ultrasound image with Gaussian noise and Wiener denoise under gray level	25.407	29.127	28.155	26.793
PSNR values in ultrasound image with Gaussian noise and Wiener denoise under gray level	34.081	33.488	33.635	33.851

NAFLD: Non-alcoholic fatty liver disease; MSE: Mean squared error; PSNR: Peak signal-to-noise ratio.

Although our image processing method had a beneficial effect on the diagnosis of different stages of NAFLD development on the ultrasound images, some limitations exist. Firstly, the statistical analysis used in our image processing method did not support the diagnosis of distinct stages of NAFLD as adequate clinical samples could not be achieved. Secondly, the sensitivity and specificity of our image processing method needs to be enhanced by a deep learning technique with enough training and testing data associated with the distinct stages of NAFLD in samples. It was reported that a “multiple-hit model” was proposed to explain the potential pathogenesis of NAFLD due to complex factors including insulin resistance, overproduction of free fatty acids, oxidative stress, hepatic inflammation, nutrition components, and gut microbiota[4,17]. Dietary intervention may be considered which could affect gut microbiota, liver enzyme activity and critical metabolic production such as bile acids[18]. Olive oil is a vegetable oil rich in polyunsaturated fatty acids, monounsaturated fatty acids, vitamins, polyphenols, and other anti-oxidant agents, and has a critical role in preventing NAFLD in patients[19]. Moreover, olive oil is considered a necessary component of the Mediterranean diet to display stable anti-oxidation and prevent chronic diseases due to high levels of polyunsaturated fatty acids and phenolic compounds with nutritional value[20]. In addition, monounsaturated fatty acids, squalene and three types of phenolic compounds with anti-oxidant properties were identified in Mediterranean diet olive oil[21]. A previous meta-analysis showed that diets with a high level of monounsaturated fatty acids decreased fasting plasma triacylglycerol levels by 19% and very-low-density lipoprotein cholesterol concentrations by 22% as well as moderately elevated high-density lipoprotein cholesterol content in patients with type 2 diabetes[22]. In a systematic review and meta-analysis it was reported that olive oil as well as other plant foods including fruits, vegetables, whole grains and nuts displayed positive effects on several markers such as central obesity, lipid profile and liver enzymes in NAFLD patients[23]. In the ideal situation, a beneficial diet for health should result in long-term weight loss with efficient reductions in steatosis and liver inflammation. The Mediterranean diet was proposed to achieve this goal and was recommended as an alternative treatment for NAFLD based on the EASL-EASD-EASO Clinical Practice Guidelines[24]. Clinically, the Mediterranean diet is rarely associated with the occurrence of NASH or metabolic syndrome in patients with NAFLD due to improvements in fat content, liver fibrosis and insulin dysfunction[25].

Besides the Mediterranean diet, physical activity and exercise have been reported to play a critical role in the treatment of NAFLD syndromes[26]. Physical exercise is usually defined as structured physical activity with a degree of intensity and frequency during planned persistence, and this type of repetitive training has become an interesting scientific subject owing to the benefits of lifestyle modification in NAFLD[27]. Physical training is considered to have better effects on weight loss compared to the Mediterranean diet while weight reductions of 5%-10% have resulted in improvements in NASH following long-term maintenance[28]. NAFLD can cause a wide range of associated complications such as obesity, insulin resistance, hypertension, etc. and these symptoms, especially obesity, also have a role in the development of NAFLD[29]. Physical activity and training are known to modulate circulating thyroid hormones such as triiodothyronine and thyroxine which could be associated with reductions in fat content, inflammation and fibrosis in the liver via insulin sensitivity[27,30]. The effects of physical exercise and activity are summarized in Figure 2, and mainly cause an increase in insulin sensitivity, energy levels and anti-oxidation, and a decrease in liver fat, body weight, inflammation and lipogenesis in NAFLD. Moreover, mitochondria are associated with the functions of reactive oxygen species, lipid metabolism and oxidation, while dysfunction of the mitochondrial network produced lipid accumulations in hepatocytes and increased fat content in the liver during the development of NAFLD[31,32]. It was proposed that appropriate hepatic mitochondrial capacity could provide anti-NAFLD effects under lipid accumulations, but over-production of activated mitochondria resulted in excessive oxidation and insulin resistance to promote NAFLD progression in obese humans[33]. Physical activity is considered to have beneficial roles in the regulation of mitochondrial function while sedentary behavior could result in the risk of NAFLD development[32]. Several animal models have shown these modulatory effects on mitochondria in the progression of NAFLD. For example, rats with high capacity running showed good aerobic capacity via elevation of hepatic mitochondrial oxidation[34]. In addition, zebrafish were used to mimic swimming exercise and alleviate the progression of NAFLD by modulating the target of mitochondria[35]. Interestingly, it has been reported that the combination of aerobic exercise and diet intervention can result in the diversification and stabilization of gut microbiota composition, while network connectivity and robustness of gut microbiota composition can be increased by a single application of exercise or diet adherence in patients with NAFLD and prediabetes[36]. Physical exercise is considered to improve gut microbiota and outcomes in patients with NAFLD similar to modulators of microecology such as probiotics, symbiotics and Mediterranean diet compositions[37].

Figure 2  Effects of physical activity and exercise on non-alcoholic fatty liver disease.

CONCLUSION

In conclusion, it is important to assess the stage of NAFLD using ultrasound with image processing as early as possible. Although conventional ultrasound is convenient and of low cost, its accuracy based on sensitivity and specificity is unsatisfactory. The Gaussian noise and Wiener denoise filters had a beneficial effect on MSE and PSNR of ultrasound images in the distinct stages of NAFLD. This method will also provide similar functions in other medical images with processing in the future. Olive oil is considered a critical component in the Mediterranean diet and has a crucial role in the prevention of NAFLD progression. Physical activity and exercise can reduce liver fat and body weight via mitochondria function. Lifestyle including dietary intervention and physical exercise can effectively manage the development of NAFLD by regulating oxidative stress, insulin resistance, and inflammation.