Link between weight-adjusted waist size and fatty liver disease and liver scarring

Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease affecting approximately 2 billion people worldwide (with a prevalence of 25%) [1]. As research progresses, fatty liver disease is thought to be associated with metabolic dysfunction and all-cause mortality is much higher in patients with fatty liver disease than in the general population [2]. NAFLD is characterised by excessive lipid accumulation in the liver in the absence of alcohol abuse and may progress further to more advanced non-alcoholic steatohepatitis, fibrosis, cirrhosis and ultimately hepatocellular carcinoma [3]. Even so, the current gold standard for assessing the degree of steatosis and fibrosis in the liver is still liver biopsy. Because liver puncture is an invasive procedure that can be harmful to the human body, it needs to be used with caution in clinical practice [4]. Liver ultrasound transient elastography (LUTE) is a test that can assess the degree of liver fibrosis and fatty liver and is used in a large number of clinical applications due to its non-invasive [5].

The risk factors for NAFLD are complex, but previous studies have demonstrated that the prevalence of NAFLD was usually associated with obesity, but a significant proportion of patients are thin, which poses a challenge for screening for NAFLD [6].

Body mass index (BMI) is a traditional indicator for determining obesity, but its inability to distinguish between lean and fat body mass [7] has led to its accuracy being questioned in recent years [8, 9]. In recent years, it has been proposed that visceral fat more accurately reflects an unfavourable metabolic profile, which is often associated with abdominal obesity [10]. WWI is a simple anthropometric indicator based on BMI, calculated as WC (cm) divided by the square root of weight (kg) [11]. WWI mainly reflects the actual situation of central obesity due to the adjustment of body weight. While the central obese group is mainly the accumulation of visceral fat, the accumulation of visceral fat can cause more endocrine and metabolic diseases [12, 13]. A strong relationship between WWI and abdominal aortic calcification was demonstrated, with a near linear relationship between them [14]. It was also found that WWI was correlated with the development of hypertension, and the higher the WWI classification, the higher risk of hypertension [15]. In addition, WWI is strongly associated with all-cause mortality and cardiovascular mortality [16, 17]. However, there are still no studies correlating WWI with NAFLD and liver fibrosis.

In the present study, we aimed to assess the association of WWI with NAFLD and liver fibrosis in US adults. To achieve these objectives, we analysed data from the 2017–2020.03 cycle of the National Health and Nutrition Examination Survey (NHANES), where waist circumference and body weight were used to assess WWI and LUTE was used for liver steatosis and fibrosis.

As mentioned earlier, the accuracy of BMI as a traditional indicator for assessing obesity has been questioned. In order to better reflect the true reality of obesity, a new obesity index was proposed and named the Weight Adjusted Waist Index (WWI) [11]. As weight is adjusted in the calculation of the WWI, this index mainly reflects weight-independent central obesity. The WWI has been shown to have better accuracy compared to BMI [15, 17, 27]. Based on the BMI formula, changes in body weight were often used to reflect fat accumulation and obesity alone in the adult population due to the stability of height. However, in recent years this notion has been questioned by researchers [28, 29]. Even more notably, when the concept of the muscle–fat–liver axis was introduced, researchers recognised that weight loss was also likely to be caused by a loss of muscle mass and that this process was often accompanied by the accumulation of visceral fat, which may reflect a more accurate level of obesity [30]. It is undeniable that NAFLD [31] is a disease closely associated with inflammation, and chronic inflammatory stimulation of the liver in particular is key to the progression of NAFLD into liver fibrosis [32]. Furthermore, obesity has been demonstrated as a low-grade inflammatory state of the organism [33, 34]. Therefore, it would be accepted that inflammation may be a key factor mediating the link between obesity and NAFLD as well as liver fibrosis. More studies have shown that central obesity was more closely associated with inflammation and metabolic disorders [11, 35]. This was therefore an advantage that our study had.

In addition, we confirmed sensitive populations with positive correlations between WWI and the dependent variables, either with NAFLD or liver fibrosis as the dependent variable. The first population characteristic that was validated was male. It is known from previous epidemiological studies that male have higher rates of NAFLD and liver fibrosis compared to female when holding other covariates constant [36, 37]. In addition, when BMI was used as a criterion for determining obesity, previous studies reported that obesity was more prevalent in women worldwide [38, 39]. However, women are predominantly peripherally obese, as they are characterised by fat deposits in the buttocks, thighs and limbs and subcutaneous tissue, and have a pear-shaped body, in contrast to men who are predominantly obese with increased visceral fat (central obesity) [9]. In fact, visceral fat is more active than subcutaneous fat, and there is a closer link between it and metabolic inflammation [40]. In addition to this, recent studies have shown that the increased fat may be more significant in the incidence of liver fibrosis in women in the abdominal obesity pattern [41]. Typically, older people have increased fat deposits in tissues such as the heart, liver and skeletal muscle [42]. However, in one study, Amdanee N performed dual-energy X-ray absorptiometry (DXA) measurements on 102 men aged 31–83 years to assess the effect of age on fat distribution (both subcutaneous and visceral fat). The results showed that the rate of subcutaneous and visceral fat accumulation was negatively correlated with age [43]. We agree that older age groups have higher rates of obesity, NAFLD and liver fibrosis, and in Table 1 our results also suggested a higher proportion of participants with a WWI > 11.11 with increasing age. However, younger groups appear to be more sensitive to increases in WWI [43]. In addition, in the elderly, there is essentially a linear relationship between WWI and LSM. This is due to the fact that liver fibrosis is already at a higher level in the elderly and therefore its changes are flatter, as demonstrated by Klisic's study [44]. Kim D reported racial differences in NAFLD and liver fibrosis in the US population. Between 2013 and 2016, the prevalence of NAFLD and liver fibrosis steadily increased in non-Hispanic whites, but the late prevalence was flat in non-Hispanic blacks [45]. Epidemiological studies suggested that adult obesity rates in the United States have steadily increased over the past decade and have stabilised at a prevalence of approximately 35%, compared with 43% and 48% for Hispanics and non-Hispanic blacks, respectively [46]. However, according to Staiano et al. they found that fat distribution characteristics differed by race, with white people being more likely to have fat distribution in the visceral organs than black people [47].

This study has important clinical value. It was the first study to use the new obesity index (WWI) to explore the association of obesity with NAFLD and liver fibrosis, and our study sample size was adequate and representative. Through subgroup analysis, we further understand the characteristics of different ages, genders and ethnicities in this correlation, which could guide us in giving different recommendations to different populations in clinical practice. However, there were still several limitations to our study. Firstly, the age of the participants in this study was above 20 years old, which leads to the possibility that our findings may not apply to participants under 20 years old. Therefore, further exploration of those under 20 years of age is needed. Secondly, this study included a number of covariates from the questionnaire which may be influenced by individual subjective factors. Third, our study was a cross-sectional study, which cannot explain causal relationships. In addition, there are numerous potential influences on obesity, NAFLD and liver fibrosis, and even though we included as many covariates as possible in our study to adjust for them in the model, there was still no guarantee that there were potential confounders leading to bias in the results. Therefore, more prospective studies are needed. Finally, the diagnosis of NAFLD and liver fibrosis in this study was not confirmed by liver biopsy, so the current conclusions need to be confirmed by follow-up studies.

In this study, WWI was positively correlated with both NAFLD and liver fibrosis in US adults, with NAFLD and liver fibrosis after LUTE discrimination as the dependent variables. The positive relationship between WWI and NAFLD was non-linear, and this positive correlation was more pronounced for WWI less than 11.44. The positive association of WWI with either NAFLD or liver fibrosis was more pronounced in white participants younger than 40 years of age.