Abstract
We investigated the risk factors of nonalcoholic fatty liver disease (NAFLD) in healthy women. This is a cross-sectional study. Healthy women who underwent physical examination were enrolled. Their basic information and medical history [including age, height, weight, body mass index (BMI)], abdominal ultrasound results, and, serological indexes [including white blood cells, platelet count, fasting blood glucose, triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDLC), uric acid (UA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutamyl transpeptidase] were collected. Univariate and multivariate regression analysis was carried out to screen the risk factors of NAFLD. ALT/AST ratio, and BMI were significantly independent risk factors for the occurrence and severity of NAFLD. In addition, TG/HDLC ratio, and UA level also had significant independent correlation with NAFLD. ALT/AST ratio, BMI, TG/HDLC ratio, and UA are independent risk factors for the occurrence and severity of NAFLD. It is suggested that obesity, hyperlipidemia, hyperuricemia and high transaminase value are closely related to NAFLD. People with such conditions should pay more attention to early screening of NAFLD to avoid disease aggravation and the occurrence and development of other complications. In clinical practice, ALT/AST, BMI, TG/HDLC, and UA level should be closely monitored, so as to facilitate the follow-up management of the disease.
Keywords: ALT/AST ratio, metabolic syndrome, nonalcoholic fatty liver disease, risk factors
1. Introduction
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by hepatic fat accumulation (the presence of steatosis in more than 5% of hepatocytes), which is induced by factors other than the known liver injury factors such as alcohol and virus infection.[1] It is a kind of metabolic stress-induced liver injury closely associated with genetic susceptibility, metabolic syndrome and insulin resistance (IR), particularly obesity and type 2 diabetes.[2] However, NAFLD is not merely a hepatic manifestation of metabolic syndrome but rather both a consequence as well a predecessor of metabolic syndrome. Compared with the general population, NAFLD patients are at increased risk of liver related, cardiovascular and all-cause mortality.[3,4] The incidence of NAFLD has been on the rise, and NAFLD has become one of the largest chronic liver diseases in the world.[5] NAFLD includes nonalcoholic fatty liver (NAFL; steatosis with or without mild inflammation), nonalcoholic steatohepatitis (NASH; a necro inflammatory subtype characterized by the presence of hepatocellular injury e.g., hepatocyte ballooning), liver fibrosis, liver cirrhosis and hepatocellular carcinoma.[6]
Most of the patients with NAFLD have no specific symptoms or have occult symptoms or are even asymptomatic; however, there may be potentially serious liver injury (including inflammation, hepatocellular injury, even fibrosis).[7] NAFLD has been associated with a large number of extrahepatic conditions, such as type 2 diabetes mellitus, atherosclerosis, cardiovascular disease, chronic kidney disease, polycystic ovarian syndrome, obstructive sleep apnea, extrahepatic malignancies, etc.[8] NAFLD is also an independent risk factor for type 2 diabetes, cardiovascular disease, and chronic kidney disease.[9,10] If not intervened early, NAFLD may aggravate and eventually lead to adverse outcomes.[11]Therefore, early screening of NAFLD is very important for early intervention and management.
Studies on NAFLD related risk factors have suggested that hypertension, hyperglycemia, hyperlipidemia, hyperuricemia and IR are risk factors for NAFLD.[12–14] Moreover, hypothyroidism, hypopituitarism, sleep apnea syndrome, and polycystic ovary syndrome are also independent risk factors for the occurrence and development of NAFLD.[15–19] Additionally, there is sex difference in the prevalence, risk factors and clinical outcomes of NAFLD.[20] The prevalence of NAFLD is higher in young males compared to females of the same age.[21] However, this trend reverses between 50 to 60 years of age.[22] It is also shown that in older individuals (above 50 years old), the prevalence of advanced fibrosis was 56% higher in women than in men.[23] However, studies specifically focusing on the risk factors of NAFLD in women, especially healthy women, are rare.
Herein, we evaluated the risk factors of NAFLD in healthy women. The population was healthy women who received physical examination. Their basic information, medical history, imaging results, and serological indexes were collected to screen for the risk factors. Our findings may provide guidance for clinical screening and diagnosis of NAFLD.
2. Materials and methods
2.1. Study subjects
This retrospective study enrolled 3959 healthy women who underwent physical examination at the health management center of The Second Hospital of Shandong University during January to December, 2020. Inclusion criteria: subjects with abdominal ultrasound showing fatty liver (with or without abnormal liver function), and with one of the following 3 items: overweight/obesity, type 2 diabetes, and manifestations of metabolic dysfunction. Exclusion criteria: subjects with excessive drinking (female: > 70 g/w); subjects with any liver disease at baseline; subjects on medication at baseline; subjects with incomplete clinical data. All subjects signed the informed consent. This study was approved by the Ethics Committee of the Second Hospital of Shandong University (approval no. KYLL-2022LW002).
2.2. Data collection
Their basic information and medical history (including age, height, weight, body mass index [BMI]), abdominal ultrasound results, and serological indexes [including white blood cells, platelet count, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TCH), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), uric acid (UA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase, etc], were collected.
2.3. Diagnosis of NAFLD
The diagnosis of NAFLD was based on the 2018 NAFLD prevention and treatment guideline[24] and 2020 international expert consensus.[25] The abdominal ultrasound findings of NAFLD were as follows: The near-field echo of liver was diffusely enhanced (“bright liver”) and stronger than that of kidney and spleen, and the far-field echo was gradually weakened; The intrahepatic duct structure was not clearly displayed; The liver was slightly to moderately enlarged and the edge was round and blunt; CDFI color Doppler flow imaging showed that the blood flow signal in the liver was reduced or difficult to display, but the blood vessels in the liver were normal; The echo of the capsule and diaphragm in the right lobe of the liver was unclear or incomplete. If there are findings of item 1 and any one of the items 2 to 5, NAFLD can be diagnosed. The degrees of NAFLD were defined as follows. If there are findings of item 1 and any one of the items 2 to 4, mild-NAFLD can be diagnosed. If there are findings of item 1 and any 2 of the items 2 to 4, moderate-NAFLD can be diagnosed. If there are findings of item 1, any 2 of the items 2 to 4, and item 5, severe-NAFLD can be diagnosed.
2.4. Statistical analysis
STATA16.0 (Stata Corporation, College Station, TX) was used for statistical analysis. The normality test (Kolmogorov-Smirov test) and the homogeneity of variance test (Levene test) were first performed on each parameter. All data of this study were of non-normal distribution, which are represented by the median and interquartile range and compared with Kruskal-Wallis or chi-square test. The subjects were grouped according to age and disease severity. Univariate logistic regression analysis was performed to screen the risk factors of NAFLD, and multivariate logistic ordered regression analysis was further conducted to evaluate the independent risk factors closely related to the occurrence and severity of NAFLD after adjusting for confounding factors. The results are expressed as odds ratio (OR) and 95% confidence interval (CI). P < .05 indicates that the difference is statistically significant.
3. Results
3.1. The basic characteristics of the study subjects
A total of 3959 subjects were included in this study, with a median age of 45 (35–55) years old. Among them, 2510 subjects were diagnosed with NAFLD by abdominal ultrasound, accounting for 63.4% of all subjects. The basic clinical data of all subjects grouped according to disease severity is shown in Table 1. As the increase of TG, TCH, BMI, UA, and FBG, the severity of NAFLD also increased, and the difference among groups was statistically significant. The subjects with NAFLD (n = 2510) were divided into 4 groups according to age (age ≤ 35 years old, 35 years old < age ≤ 50 years old, 50 years old < age ≤ 65 years old, and, age > 65 years old). The characteristics of these subjects are shown in Table 2. The subgroups of 35 years old < age ≤ 50 years old (65%) and 50 years old < age ≤ 65 years old (79%) had relatively higher NAFLD prevalence.
Table 1.
Baseline characteristics of study subjects classified by different degrees of NAFLD.
| Parameter | Total | Non-NAFLD | Mild-NAFLD | Moderate-NAFLD | Severe-NAFLD | P value |
|---|---|---|---|---|---|---|
| (n = 3959) | (n = 1449) | (n = 1851) | (n = 612) | (n = 47) | ||
| Age (yr) | 45 (35–55) | 37 (32–48) | 49 (38–57) | 49 (40–58) | 49 (37–56) | <.001 |
| WBC (10^9/L) | 6.32 (5.35–7.42) | 5.81 (4.99–6.89) | 6.5 (5.56,7.58) | 6.78 (5.82–7.89) | 7.17 (5.84–8.59) | <.001 |
| PLT (10^9/L) | 266 (231–307) | 251 (219–289) | 272 (236–311) | 286 (246–326) | 284 (256–329) | <.001 |
| TG (mmol/L) | 1.22 (0.85–1.75) | 0.84 (0.65–1.18) | 1.39 (1.05–1.91) | 1.64 (1.19–2.37) | 1.99 (1.36–3.00) | <.001 |
| TCH (mmol/L) | 4.67 (4.1–5.34) | 4.45 (3.95–5.04) | 4.79 (4.19–5.42) | 4.96 (4.34–5.78) | 5.00 (4.19–5.73) | <.001 |
| HDLC (mmol/L) | 1.32 (1.14–1.55) | 1.51 (1.3–1.75) | 1.24 (1.1–1.42) | 1.2 (1.08–1.38) | 1.2 (1.03–1.30) | <.001 |
| LDLC (mmol/L) | 2.81 (2.31–3.41) | 2.59 (2.15–3.09) | 2.93 (2.4–3.5) | 3.13 (2.55–3.67) | 2.89 (2.39–3.64) | <.001 |
| ALT (U/L) | 15 (11–21) | 11 (9–15) | 16 (12–21) | 23 (16–32) | 27.5 (20–37) | <.001 |
| AST (U/L) | 17 (14–20) | 15 (13–18) | 17 (14–21) | 20 (16–25) | 22 (20–29) | <.001 |
| GGT (U/L) | 17 (13–24) | 13 (10–17) | 19 (15–26) | 24 (19–34) | 29 (20–36) | <.001 |
| UA (mg/dL) | 4.69 (3.93–5.48) | 3.95 (3.44–3.95) | 5.01 (4.32–5.78) | 5.49 (4.75–6.25) | 5.65 (4.79–6.47) | <.001 |
| BMI (kg/m²) | 24.84 (22.46–27.49) | 22.3 (20.43–24.37) | 25.85 (23.88–27.89) | 28.12 (25.58–30.47) | 30.11 (27.83–32.35) | <.001 |
| FBG (mmol/L) | 5.05 (4.72–5.5) | 4.88 (4.63–5.18) | 5.1 (4.77–5.57) | 5.38 (4.99–6.2) | 6.06 (5.32–7.23) | <.001 |
| ALT/AST | 0.88 (0.71–1.12) | 0.75 (0.64–0.92) | 0.93 (0.78–1.14) | 1.14 (0.92–1.38) | 1.74 (1.02–2.72) | <.001 |
| TG/HDLC | 0.92 (0.57–1.43) | 0.56 (0.40–0.85) | 1.13 (0.79–1.64) | 1.30 (0.91–2.12) | 1.2 (0.97–1.52) | <.001 |
ALT = alanine aminotransferase, AST = aspartate aminotransferase, BMI = body mass index, FBG = fasting blood glucose, GGT = glutamyl transpeptidase, HDLC = High-density lipoprotein cholesterol, LDLC = low-density lipoprotein cholesterol, NAFLD = nonalcoholic fatty liver disease, PLT = Platelet count, TCH = Total cholesterol, TG = triglycerides, UA = uric acid, WBC = white blood cells.
Table 2.
Baseline characteristics of subjects with NAFLD classified by age.
| Parameter | Total | ≤35 y | 35–50 y | 50–65 y | >65 y | P value |
|---|---|---|---|---|---|---|
| (n = 2510) | (n = 441) | (n = 968) | (n = 893) | (n = 208) | ||
| Age (yr) | 49 (38–57) | 31 (27–33) | 44 (39–48) | 57 (54–61) | 69 (67–73) | <.001 |
| BMI (kg/m²) | 26.40 (24.34–28.65) | 26.81 (25.01–29.39) | 26.49 (24.24–28.91) | 25.88 (24.26–28.19) | 26.50 (24.30–29.33) | <.001 |
| WBC (10^9/L) | 6.57 (5.64–7.7) | 7.18 (6.09–8.10) | 6.7 (5.81–7.8) | 6.16 (5.33–7.25) | 6.31 (5.3–7.7) | <.001 |
| PLT (10^9/L) | 276 (239–315) | 299 (259–327) | 288 (247–331) | 263 (226–299) | 246 (220–283) | <.001 |
| TG (mmol/L) | 1.46 (1.09–2.01) | 1.20 (0.92–1.61) | 1.38 (1.06–1.91) | 1.68 (1.24–2.26) | 1.60 (1.22–2.13) | <.001 |
| TCH (mmol/L) | 4.83 (4.23–5.52) | 4.30 (3.88–4.82) | 4.73 (4.19–5.35) | 5.24 (4.58–5.89) | 4.91 (4.2–5.54) | <.001 |
| HDLC (mmol/L) | 1.23 (1.09–1.41) | 1.20 (1.06–1.34) | 1.23 (1.08–1.39) | 1.26 (1.11–1.44) | 1.28 (1.1–1.44) | <.001 |
| LDLC (mmol/L) | 2.97 (2.46,3.56) | 2.62 (2.31–3.03) | 2.95 (2.42–3.45) | 3.26 (2.66,3.79) | 2.93 (2.32––3.56) | <.001 |
| ALT (U/L) | 17 (13–24) | 16 (11–23) | 16 (12–24) | 19 (14–25) | 16 (12–23) | <.001 |
| AST (U/L) | 18 (15–22) | 16 (14–20) | 17 (14–21) | 19 (16–23) | 19 (15–24) | <.001 |
| GGT (U/L) | 20 (16–28) | 18 (14–27) | 20 (15–27) | 21 (16–29) | 20 (16–28) | <.001 |
| UA (mg/dL) | 5.14 (4.42–5.91) | 5.31 (4.61–6.17) | 5.09 (4.35–5.83) | 5.07 (4.44–5.87) | 5.12 (4.40–6.00) | <.001 |
| FBG (mmol/L) | 5.18 (4.83–5.71) | 4.88 (4.57–5.23) | 5.09 (4.79–5.57) | 5.37 (4.96–5.94) | 5.54 (5.51–6.68) | <.001 |
| ALT/AST | 1 (0.8–1.20) | 1.05 (0.79–1.25) | 1 (0.81–1.23) | 1 (0.81–1.2) | 0.87 (0.72–1) | <.001 |
| TG/HDLC | 1.18 (0.83–1.74) | 1.02 (0.75–1.40) | 1.12 (0.83–1.66) | 1.33 (0.87–1.92) | 1.32 (0.83–1.75) | <.001 |
ALT = alanine aminotransferase, AST = aminotransferase, BMI = body mass index, CI = confidence interval, FBG = fasting blood glucose, GGT = glutamyl transpeptidase, HDLC = high-density lipoprotein cholesterol, LDLC = low-density lipoprotein cholesterol, NAFLD = nonalcoholic fatty liver disease, OR = odds ratio, PLT = platelet count, TCH = total cholesterol, TG = triglyceride, UA = uric acid, WBC = white blood cells.
3.2. Screening of risk factor for NAFLD
Univariate logistic regression analysis showed that the main risk factors of NAFLD were ALT/AST, UA, and FBG (Table 3). The OR values were 14.67 (95% CI:11.17, 19.27), 3.76 (95% CI:3.41, 4.13) and 2.15 (95% CI:1.92,2.41), respectively. This suggested that the risk of NAFLD was significantly related with high levels of ALT/AST, UA, and FBG. The levels of ALT/AST and UA were more closely related with NAFLD. The risk of NAFLD increased by nearly 14 times and 3 times for each increase of ALT/AST and UA levels.
Table 3.
Risk factors associated with occurrence of NAFLD by univariate analysis.
| Parameter | OR (95% CI) | P value |
|---|---|---|
| ALT/AST | 14.67 (11.17, 19.27) | <.001 |
| UA (mg/dL) | 3.76 (3.41, 4.13) | <.001 |
| FBG (mmol/L) | 2.15 (1.92, 2.41) | <.001 |
| LDLC (mmol/L) | 1.81 (1.65, 1.99) | <.01 |
| BMI (kg/m2) | 1.56 (1.51, 1.61) | <.001 |
| TCH (mmol/L) | 1.51 (1.41, 1.63) | <.001 |
ALT = alanine aminotransferase, AST = aspartate aminotransferase, BMI = body mass index, CI = confidence interval, FBG = fasting blood glucose, LDLC = low-density lipoprotein, OR = odds ratio, NAFLD = nonalcoholic fatty liver disease, TCH = Total cholesterol, UA = uric acid.
3.3. Screening of risk factors related to NAFLD severity
Univariate regression analysis showed that ALT/AST, TG, and LDLC were significantly associated with NAFLD severity (Table 4), suggesting that NAFLD severity was significantly related with high levels of ALT/AST, TG, and LDLC. The relationship between ALT/AST and NAFLD severity was closer. The risk of moderate and severe-NAFLD increased about 4 times for each unit of ALT/AST.
Table 4.
Univariate analysis of the risk factors associated with NAFLD severity.
| Parameter | OR (95% CI) | P value |
|---|---|---|
| ALT/AST | 5.27 (4.01, 6.92) | <.001 |
| TG (mmol/L) | 1.38 (1.25, 1.52) | <.001 |
| LDLC (mmol/L) | 1.30 (1.16, 1.46) | <.001 |
| TG/HDLC | 1.28 (1.17, 1.41) | <.001 |
| BMI (kg/m2) | 1.25 (1.21, 1.29) | <.001 |
| TCH (mmol/L) | 1.24 (1.13, 1.37) | <.001 |
| FBG (mmol/L) | 1.23 (1.17, 1.30) | <.001 |
ALT = alanine aminotransferase, AST = aspartate aminotransferase, BMI = body mass index, CI = confidence interval, FBG = fasting blood glucose, HDLC = High-density lipoprotein, LDLC = low-density lipoprotein, OR = odds ratio, NAFLD = nonalcoholic fatty liver disease, TCH = Total cholesterol, TG = triglycerides.
3.4. Screening of independent risk factors associated with NAFLD severity
Multivariate ordered logistic regression analysis was performed. The confounding factors (including age, BMI, UA, TCH, TG, HDLC, LDLC, FBG, ALT, AST, etc.) were adjusted. The results showed that the independent risk factors were different in different age groups, as shown in Table 5.
Table 5.
Multivariate logistic regression analysis of independent risk factors for NAFLD.
| Parameter | Total (n = 1942) | ≤35y (n = 281) | 35–50y (n = 686) | 50–65y (n = 787) | >65 y (n = 188) |
|---|---|---|---|---|---|
| OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | |
| BMI (kg/m2) | 1.20 (1.16, 1.24)‡ | 1.17 (1.08, 1.27)‡ | 1.23 (1.17, 1.29)† | 1.25 (1.17, 1.33)† | 1.21 (1.09, 1.36)‡ |
| FBG (mmol/L) | 1.16 (1.10, 1.23)‡ | ------- | ------- | 1.17 (1.07, 1.28)† | ------- |
| GGT (U/L) | ------- | 1.04 (1.01, 1.07)† | ------- | ------- | ------- |
| UA (mg/dL) | 1.29 (1.17, 1.42)‡ | ------- | 1.31 (1.11, 1.55)‡ | 1.34 (1.14, 1.57)‡ | ------- |
| ALT/AST | 3.71 (2.70, 5.12)‡ | 2.98 (1.31, 6.74)† | 3.03 (1.79, 5.11)† | 4.21 (2.36, 7.50)‡ | 6.97 (1.76, 27.63)† |
| TG/HDLC | 1.11 (1.07, 1.15)‡ | 1.59 (1.05, 2.40)* | 1.15 (1.05, 1.26)† | 1.09 (1.04, 1.14)‡ | ------- |
-------: means that this factor was not included in the subgroup analysis.
ALT = alanine aminotransferase, AST = aminotransferase, BMI = body mass index, CI = confidence interval, FBG = fasting blood glucose, GGT = glutamyl transpeptidase, HDLC = high-density lipoprotein cholesterol, NAFLD = nonalcoholic fatty liver disease, OR = odds ratio, TG = triglyceride, UA = uric acid.
P < .05.
P < .01.
P < .001.
For the group of ≤ 35 years old, the ALT/AST (OR 2.98, 95% CI:1.31, 6.74) and TG/HDLC (OR 1.59, 95% CI:1.05, 2.40) were identified as independent risk factors for NAFLD severity (P < .05). For each increase of ALT/AST and TG/HDLC, the risk of NAFLD severity increased by about 2 times and 59%, respectively.
For the group of 35 to 50 years old, the significant independent risk factors for NAFLD severity included ALT/AST (OR 3.03, 95% CI: 1.79, 5.11) and UA (OR 1.31, 95% CI: 1.11, 1.55) (P < .01). It is suggested that the severity of NAFLD might increase about 2 times and 31% for each increase of ALT/AST and UA, respectively.
For the group of 50 to 65 years old, the ALT/AST (OR 4.21, 95% CI: 2.36,.50), BMI (OR 1.25, 95% CI: 1.17,1.33) and UA (OR 1.34, 95% CI: 1.14, 1.57) were significantly related with NAFLD severity (P < .001). For each increase of ALT/AST, BMI, and UA, the severity of NAFLD increased by about more than 3 times, 25% and 34%, respectively.
For the group of > 65 years old, the ALT/AST (OR 6.97, 95% CI: 1.76, 7.63) was significantly associated with NAFLD severity (P < .01), suggesting that for each increase of ALT/AST, the risk of NAFLD severity increased by about 6 times.
4. Discussion
The prevalence of NAFLD in the global population is increasing day by day. It is closely related to metabolic disorders, and is a risk factor for diabetes, cardiovascular diseases and chronic kidney diseases.[9,10] NAFLD has become one of the major chronic liver diseases threatening the health of adults and adolescents and affecting the quality of life.[26] This study focused on the females selected from those underwent physical examination. The risk factors of NAFLD were evaluated in different age groups of this population. We found that ALT/AST, BMI, TG/HDLC, and UA were independent risk factors of NAFLD. In particular, the independent relationship of ALT/AST and BMI with NAFLD were more common and significant.
It is shown that ALT/AST is independently associated with hepatic steatosis.[27] In the non-obese population, ALT/AST is related to the incidence of NAFLD and it can predict the incidence of fatty liver.[28] However, the relationship between ALT/AST and NAFLD in the healthy population, especially the female population, is rarely reported. In this study, we showed that ALT/AST had a significant independent relationship with NAFLD in all age groups of healthy women, especially in the group older than 65 years old (OR: 6.97). The possible mechanisms for this relationship are as follows. First, it is reported that ALT/AST is related to fat accumulation,[29] and ALT/AST can better predict hepatic steatosis than the ALT value alone.[30] Second, ALT/AST is also closely related to IR and is an effective biomarker of IR.[31] Importantly, many studies have shown that IR plays an important role in the pathogenesis of NAFLD,[32] as well as in the aggravation of NAFLD.[33] It can be seen that ALT/AST is related to hepatic fat accumulation and IR. Thus, ALT/AST may predict and screen NAFLD.
Our study also showed that BMI had remarkably independent relationship with NAFLD severity in all age groups. Previous studies have also shown that obesity is a risk factor for NAFLD severity and advanced NAFLD (including NASH, fibrosis, hepatic cell carcinoma etc.).[34,35] Moderate weight loss can improve liver fat accumulation and BMI has been recognized as the main risk factor for NAFLD.[36] These findings suggest that weight control is very important to reduce the severity of fatty liver and avoid its progression.
In addition, we found that UA had a significant independent correlation with the incidence and severity of NAFLD, which is consistent with previous study.[37] Specifically, UA may be involved in NAFLD through the following mechanisms. First, it has been shown that hepatocytes exposed to UA had a higher tendency to develop endoplasmic reticulum stress and increased lipogenesis, leading to hepatic fat accumulation.[38] Second, a high UA level can trigger endothelial dysfunction and IR.[39] Third, hyperuricemia is related to oxidative stress, and systemic inflammation.[40] Thus, hyperuricemia is associated with fat accumulation, IR, oxidative stress and systemic inflammation, which are basic features of NAFLD.[41]
Furthermore, consistent with previous finding,[42] our present study showed that TG/HDLC was an independent risk factor of NAFLD occurrence and severity. On the 1 hand, IR may be responsible for the association between TG/HDLC and NAFLD. Hypertriglyceridemia has been suggested to accelerate IR, especially when it is accompanied by low serum HDLC concentrations.[43] TG/HDLC is found to be closely associated with IR and has been recommended as a clinical indicator of IR.[44] IR promotes NAFLD by inducing lipolysis of adipose tissue TG and de novo synthesis of TG in the liver.[45] On the other hand, adiponectin may play a role in the association between TG/HDLC and NAFLD. It is shown that adiponectin increases serum HDLC and conversely lowers serum TG,[46] thus reducing adiponectin may lead to increased TG/HDLC. Low serum adiponectin has been shown to be a predictor of progression of NAFLD.[47] Thus, increased TG/HDLC is associated with IR and lower serum adiponectin, which further promotes progression of NAFLD.
Finally, our results suggested that the risk factors related to NAFLD were different in different age groups. These findings are distinctive, implying that age and sex should be given full consideration in managing NAFLD patients. In the ≤ 35-year-old group, TG/HDLC was more closely related to the occurrence and severity of NAFLD, indicating that it is more important to reduce TG level and improve HDLC level. In the 35 to 50 and 50 to 65 age groups, BMI and UA were identified as significant independent risk factors of NAFLD severity. This suggests that it is important to control body weight and UA level in these age groups. In the age group of > 65 years old, ALT/AST had the most significant relationship with the severity of NAFLD. Therefore, clinicians should focus on different indicators for the monitoring and management of different age groups, so as to facilitate the screening, prevention and treatment of NAFLD.
There are some limitations in this study. First, liver biopsy was not performed, and thus histopathological evidence as well as classification of inflammation and fibrosis was lacking. Second, this study was a cross-sectional study and no further prospective follow-up was performed. Thus, the causal relationship between the risk factors and NAFLD cannot be indicated. Third, this study used conventional 2-dimensional ultrasound to classify the fatty liver. However, the liver fat content was not further quantified. Further studies are warranted.
In summary, we screened the independent risk factors for the occurrence and severity of NAFLD in healthy women. We found that high levels of ALT/AST, TG/HDLC, BMI, and UA were independent risk factors for the occurrence and severity of NAFLD. Among them, ALT/AST had the most significant relationship with NAFLD. These findings suggest that the occurrence and development of NAFLD are closely related to elevated hepatic enzyme, lipid metabolism dysfunction, obesity, and UA metabolism disturbance. Women with such risk factors should pay attention to NAFLD screening for early intervention and management to prevent aggravation of NAFLD.
Author contributions
Conceptualization: Hui Guan, Mei Wu.
Data curation: Hui Guan, Fang Cheng.
Formal analysis: Hui Guan, Guangrui Shao, Fang Cheng, Pingjuan Ni.
Investigation: Hui Guan, Guangrui Shao, Fang Cheng, Pingjuan Ni.
Methodology: Hui Guan.
Project administration: Mei Wu.
Software: Guangrui Shao.
Supervision: Mei Wu.
Validation: Hui Guan.
Visualization: Mei Wu.
Writing – original draft: Hui Guan.
Writing – review & editing: Mei Wu.
Abbreviations:
- ALT
- alanine aminotransferase
- AST
- aminotransferase
- BMI
- body mass index
- CI
- confidence interval
- HDLC
- high-density lipoprotein cholesterol
- IR
- insulin resistance
- LDLC
- low-density lipoprotein cholesterol
- NAFLD
- nonalcoholic fatty liver disease
- OR
- odds ratio
- TCH
- total cholesterol
- TG
- triglyceride
- UA
- uric acid
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
The authors have no funding and conflicts of interest to disclose.
This study was approved by the Ethics Committee of the Second Hospital of Shandong University (approval no. KYLL-2022LW002).
How to cite this article: Guan H, Shao G, Cheng F, Ni P, Wu M. Risk factors of nonalcoholic fatty liver disease in healthy women. Medicine 2023;102:31(e34437).
Contributor Information
Hui Guan, Email: 44072926@qq.com.
Guangrui Shao, Email: sdshgr63@sina.com.
Fang Cheng, Email: chengfang201715@163.com.
Pingjuan Ni, Email: xiaoniba669@126.com.
References
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