Risk Factors and Diagnostic Markers for Fatty Liver and Metabolic Syndrome Among Young Adults: Insights from a Community-Based Investigation

doi:10.21203/rs.3.rs-4706149/v1

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Risk Factors and Diagnostic Markers for Fatty Liver and Metabolic Syndrome Among Young Adults: Insights from a Community-Based Investigation

https://doi.org/10.21203/rs.3.rs-4706149/v1

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Background

There is a growing incidences of hepatosteatosis and metabolic syndrome in young adults worldwide. This study aimed to address these gaps by systematically evaluating simple indices in clinical practice to strengthen the prediction and prevention of hepatosteatosis in young adults.

Methods

Of the 4,067 young adults (20–40 years old) who underwent a community health check-up between March and December 2022, 3,796 (93%) were eligible for analysis. The characteristics of the participants with and without moderate-to-severe fatty liver were compared using SPSS 26 with two-tailed tests. Multivariable logistic regression model and AUC were performed to assess the correlation between fatty liver and associated factors in this study.

Results

Those prevalence was significant, with 24.9%, 19.8%, and 7.1% of the participants having mild, moderate, and severe fatty liver, respectively. The alanine transaminase/aspartate transaminase ratio (ALT/AST) showed a good diagnostic performance for fatty liver (AUC = 79.1%, 95% CI = 77.8 to 80.4%) and cutoff value > 1.3 for ALT/AST ratio, whereas blood cell parameters were less effective. Multivariable analysis identified male (odds ratio [OR] 1.44, 95% CI 1.20–1.73), elder age (OR 1.06, 95% CI 1.05–1.08), ALT/AST > 1.3 (OR 6.13, 95% CI 5.15–7.30) associated with a higher risk of significant fatty liver while smoking and betel chewing additionally associated with metabolic syndrome. By contrast, regular exercise (OR 0.79, 95% CI 0.64–0.93) and dental scaling (OR 0.81, 95% CI 0.69–0.96) were significantly associated with a lower risk.

Conclusions

Beyond male, age, education, exercise and dental scaling, our study found ALT/AST ratios > 1.3 might be significantly correlated with moderate-to-severe hepatosteatosis and metabolic syndrome among young adults. Further large-scale and long-term observations are required to verify these findings and understand the underlying mechanisms.

fatty liver

hepatosteatosis

lifestyle

metabolic syndrome

transaminase

Hepatosteatosis, commonly known as fatty liver disease, is a burgeoning global health concern intricately associated with the increasing prevalence of obesity, metabolic syndrome (MetS), and related metabolic disorders [1, 2]. Taiwan has a prevalence of non-alcoholic fatty liver disease (NAFLD) of approximately 48.4% and a more substantial non-alcoholic steatohepatitis (NASH) burden than greater China, with an overall prevalence of 2.4–6.1% [3, 4] and even higher than the worldwide analysis of NAFLD, estimated to be 32.4% [5]. Due to the abnormal accumulation of triglycerides within hepatocytes, hepatosteatosis can vary in severity, ranging from benign hepatic steatosis to more ominous conditions such as NAFLD and NASH. Early detection and accurate risk stratification of hepatosteatosis are essential for the effective intervention and prevention of disease progression.

Although abdominal ultrasonography remains a cornerstone in diagnosing hepatic steatosis, its diagnostic accuracy, particularly in detecting mild-to-moderate fatty liver, may vary [6, 7]. Consequently, there is a growing interest in exploring simple, noninvasive indices derived from routine laboratory parameters as adjunctive tools for predicting hepatosteatosis and fatty liver disease. Serum biomarkers, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and various inflammatory markers have emerged as potential indicators of hepatic, hepatocellular, and systemic inflammation [8]. These simple indices offer a pragmatic approach to risk assessment and prognostication, leveraging readily available clinical data to inform clinical decision-making. The ALT/AST ratio in Chinese individuals without obesity and NAFLD at baseline was closely associated with the risk of developing new-onset NAFLD [9]. In addition, high ALT activity appears to be a predictor of mortality and cardiovascular disease [10] in community populations [11], while elevated liver enzymes are associated with higher C-reactive protein (CRP) concentrations and systemic inflammation [12]. Despite the increasing recognition of the utility of simple indices in predicting hepatosteatosis, significant knowledge gaps persist regarding their diagnostic accuracy, optimal cutoff values, and comparative performance against established imaging modalities such as ultrasonography. Furthermore, the influence of demographic, lifestyle, and clinical factors on the predictive value of these indices remains poorly understood, necessitating a comprehensive investigation within diverse patient populations.

This study aimed to address these knowledge gaps by systematically evaluating simple indices for predicting hepatosteatosis diagnosed using echography. By elucidating the diagnostic accuracy and clinical implications of AST, ALT, inflammatory markers, and other simple indices, this study aimed to inform clinical practice, optimize risk stratification strategies, and guide the development of tailored interventions for patients at risk for fatty liver disease.

This study explored the health needs of young adults after community health check-ups in rural areas. Community-based annual health check-ups were conducted in collaboration with a local hospital, and participants were selected using convenience sampling between March and December 2022 in the western coast of Yunlin County, Taiwan. The research team described the study procedures, e.g., fasting blood samples after fasting for 8 h overnight. The inclusion criteria were as follows: (1) age 20–40 years; (2) ability to complete questionnaires in Mandarin via face-to-face interviews; and (3) agreement to provide informed consent. If participants were unable to complete the health surveys, their laboratory data were excluded from the study.

Measures

(a) Demographic characteristics: sex, age, and education level.

(b) Health-related behaviors:

Adopting healthy diet was assessed using the frequency of at least three portions of vegetables and two portions of fruit per day, with responses categorized as “less: never or seldom” and “often: usually or always.”

Regular exercise was assessed using the participants’ responses that they [usually/always (often): seldom/never (less)] engaged in exercise for at least 30 min/day or three times per week.

Substance uses were assessed, including current/former using cigarette smoking, alcohol drinking, and betel nuts chewing, with responses categorized as “never” vs. “yes: former or current user.

Oral health and oral hygiene behaviors were assessed with (1) the frequency of using dental ﬂoss before bed, (2) uptake dental scaling each half or one year, with responses of “less: never or seldom” or “often: usually or always,” and (3) counting the number of natural teeth by self-reported.

(c) Cardiometabolic risk factors were assessed, including (1) central obesity was measured with waist circumference in males/females > 90/80 cm, (2) systolic/diastolic blood pressure > 130/85 mmHg, (3) fasting serum blood glucose (FBG) > 100 mg/dL, (4) fasting serum triglyceride (TG) > 150 mg/dL, and (5) fasting serum high-density lipoprotein-cholesterol (HDL-C) in males/females < 40/50 mg/dL. The presence of three or more of the above components was classified as MetS.

(d) Fatty liver was assessed using ultrasound examinations performed by a team of gastrointestinal physicians and radiologists with 6–10 years of experience in abdominal ultrasonography. The severity of fatty liver was categorized into four grades (0–3): Grade 0, normal liver; Grade 1, mild fatty liver; Grade 2, medium-grade diffuse increase in hepatic echogenicity; and Grade 3, moderate-to-severe fatty liver and marked increase in fine echoes in the parenchyma with poor or no visualization of the intrahepatic vessel borders, diaphragm, and posterior right lobe of the liver.

Statistical Analyses

The characteristics of participants with and without moderate-to-severe fatty liver were compared using the chi-square test for categorical variables and the independent sample t-test for continuous variables. The distribution of liver enzymes and blood cell parameters was skewed and was compared using the Mann–Whitney U test. The performance of liver enzymes and blood cell parameters in discriminating moderate-to-severe fatty liver from MetS was evaluated using the area under the receiver operating characteristic curve (AUC). The corresponding optimal cut-off point was determined using the Youden index. Finally, the factors associated with moderate-to-severe fatty liver and MetS were identified using a multivariable logistic regression model. All tests were 2-tailed, and P <0.05 was considered statistically significant. Data were analyzed using SPSS version 26 (IBM SPSS Inc., Chicago, Illinois, USA).

Between March and December 2022, 11,225 adult participants underwent a community health check-up. Of these, 4,067 participants were young adults aged 20–40 years. After excluding those with missing data (e.g., information on fatty liver and MetS), 3,796 (93.3%) participants were eligible for the analysis. Among the participants analyzed, 1,832 (48.3%) were diagnosed with no fatty liver, whereas 945 (24.9%), 751 (19.8%), and 268 (7.1%) were diagnosed with mild, moderate, and severe fatty liver, respectively (Data not shown).

Characteristics of the participants

Table 1 lists the characteristics of the participants. The mean age was 30.4 years, and 44.7% were male. Only 1199 (31.6%) participants exercised regularly. The prevalence rates of smoking, alcohol consumption, and betel chewing were 14.4%, 11.4%, and 2.9%, respectively. The average number of teeth was 28.8, and almost all participants (94.5%) had ≥ 24. Approximately half the participants used dental floss (52.5%) and underwent regular dental scaling (61.7%). The prevalence of MetS was 13.8% (n = 525). The distribution of liver enzymes and blood cells is also presented.

Table 1

The demographics of the participants with and without moderate/severe fatty liver
Variable	Total (n = 3,796)	Moderate/Severe (n = 1,019)	None/Mild (n = 2,777)	P value
Demographics
Male	1,698 (44.7)	620 (60.8)	1,078 (38.8)	< 0.001
Age, year	30.4 ± 6.1	32.0 ± 5.8	29.8 ± 6.1	< 0.001
Education level, year	14.8 ± 2.1	14.5 ± 2.2	14.9 ± 2.1	< 0.001
Life style
Intake vegetable ≥ 3 portions per day	2,272 (59.9)	603 (59.2)	1,669 (60.1)	0.627
Intake fruit ≥ 2 portions per day	1,931 (50.9)	496 (48.7)	1,435 (51.7)	0.107
Regular exercise	1,199 (31.6)	273 (26.8)	926 (33.3)	< 0.001
Smoking	548 (14.4)	198 (19.4)	350 (12.6)	< 0.001
Alcoholic drinking	432 (11.4)	152 (14.9)	280 (10.1)	< 0.001
Betel chewing	109 (2.9)	48 (4.7)	61 (2.2)	< 0.001
Oral hygiene
Number of teeth	28.8 ± 3.3	28.7 ± 3.6	28.9 ± 3.2	0.032
Number of teeth ≥ 24	3,589 (94.5)	949 (93.1)	2,640 (95.1)	0.024
Using dental floss	1,993 (52.5)	522 (51.2)	1,471 (53.0)	0.341
Dental scaling	2,342 (61.7)	558 (54.8)	1,784 (64.2)	< 0.001
Data of metabolic syndrome (MetS)
Waist circumference, cm	79.1 ± 12.5	91.6 ± 11.0	74.5 ± 9.6	< 0.001
Systolic blood pressure, mmHg	119.6 ± 16.9	131.2 ± 17.0	115.3 ± 14.8	< 0.001
Fasting glucose, mg/dL	94.3 ± 17.4	100.7 ± 28.0	91.9 ± 10.4	< 0.001
Triglyceride, mg/dL	100.6 ± 80.8	143.6 ± 107.7	84.8 ± 61.2	< 0.001
High–density lipoprotein, mg/dL	58.4 ± 14.6	49.3 ± 11.1	61.8 ± 14.3	< 0.001
Cardiometabolic factor
Central obesity ¹	1,161 (30.6)	728 (71.4)	433 (15.6)	< 0.001
Blood pressure ²	957 (25.2)	512 (50.2)	445 (16.0)	< 0.001
Fasting glucose ³	669 (17.6)	334 (32.8)	335 (12.1)	< 0.001
Triglyceride ⁴	558 (14.7)	344 (33.8)	214 (7.7)	< 0.001
High–density lipoprotein ⁵	577 (15.2)	307 (30.1)	270 (9.7)	< 0.001
Metabolic syndrome (MetS) ⁶	525 (13.8)	394 (38.7)	131 (4.7)	< 0.001
Number of components of MetS	1.0 ± 1.2	2.2 ± 1.3	0.6 ± 0.9	< 0.001
Liver enzymes
AST, U/L	17 [14, 21]	20 [16, 25]	16 [14, 19]	< 0.001
ALT, U/L	19 [13, 30]	33 [21, 51]	16 [12, 24]	< 0.001
ALT / AST ratio	1.14 [0.90, 1.56]	1.60 [1.25, 2.05]	1.05 [0.84, 1.33]	< 0.001
Blood cell
NLR	1.75 [1.36, 2.21]	1.84 [1.47, 2.32]	1.71 [1.34, 2.16]	< 0.001
PLR	126.5 [104.3, 153.9]	123.7 [101.2, 148.2]	127.6 [104.9, 156.2]	0.001
MLR	0.17 [0.13, 0.20]	0.17 [0.14, 0.21]	0.16 [0.13, 0.20]	0.001
WBC, count×10³	6.3 [5.4, 7.6]	7.2 [6.1, 8.4]	6.1 [5.2, 7.2]	< 0.001
Abbreviation: AST, aspartate aminotransferase; ALT, alanine transaminase; NLR, neutrophil–to–lymphocyte ratio; PLR, platelet to lymphocyte ratio; MLR, Monocyte–to–lymphocyte ratio; WBC, white blood cell;
Data are presented as frequency (percentage), mean ± standard deviation or median [25th, 75th percentiles];
¹ Waist circumference, male > 90 cm, female > 80 cm;
² Systolic blood pressure > 130 mmHg;
³ Fasting glucose ≥ 100 mg/dL;
⁴ Triglyceride ≥ 150 mg/dL;
⁵ High–density lipoprotein, male < 40 mg/dL, female < 50 mg/dL;
⁶ Number of component of MetS ≥ 3 components.

The participants’ characteristics with and without moderate-to-severe fatty liver disease were further compared. Compared to participants with no or mild fatty liver, those with moderate or severe fatty liver were more likely to be male (60.8% vs. 38.8%), older, had a lower education level, were less likely to exercise regularly, had more substance use, had fewer teeth, were less likely to receive regular dental scaling, had poor MetS data, had more abnormalities of MetS components, had greater levels of AST, ALT, and ALT/AST ratio, higher neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, and white blood cell (WBC), and lower platelet-lymphocyte ratio (Table 1).

Diagnostic properties of liver enzymes and blood cell parameters

Table S1 summarizes the diagnostic properties of liver enzymes and blood cell parameters for discriminating between moderate-to-severe fatty liver and MetS. The results showed that the ALT (AUC 78.3%, 95% confidence interval [CI] 77.0–79.6%) and ALT/AST ratios (AUC 79.1%, 95% CI 77.8–80.4%) had satisfactory performance (Figure 1A). The corresponding optimal ALT cutoff was >22 U/L, and it was >1.3 for ALT/AST ratio, which had consistent effects among different subgroups. (Table S2) In contrast, the discrimination performance of blood cell parameters was poorer than that of liver enzymes (Figure 1B). However, the performance of WBC was relatively better among the blood cell parameters (AUC 68.6%, 95% CI 67.1–70.1%) with the corresponding optimal cutoff by 6.7 count×10³. The results for MetS were generally consistent with those for moderate to severe fatty liver disease (Table 1S and Figure 2A-2B).

Association factors of moderate to severe fatty liver and MetS

The multivariable logistic regression model showed that male sex (odds ratio [OR] 1.44, 95% CI 1.20–1.73), older age (OR 1.06, 95% CI 1.05–1.08), ALT/AST > 1.3 (OR 6.13, 95% CI 5.15–7.30, p<0.001) were significantly associated with a higher risk of moderate-to-severe fatty liver. By contrast, taking regular exercise (OR 0.78, 95% 0.64–0.93, p=0.007), and undergoing regular dental scaling (OR 0.81, 95% CI 0.69–0.96, p=0.016) were significantly associated with a lower risk of moderate-to-severe fatty liver (Table 2). Factors associated with MetS were identified, including ALT/AST > 1.3, male sex, age, educational level, regular exercise, and dental scaling. However, the results further demonstrated that both smoking (OR 1.55, 95% CI 1.16–2.07, p=0.003) and betel chewing (OR 1.77, 95% CI 1.07–2.94, p=0.026) were also significantly associated with a higher risk of MetS (Table 3). The Odds ratio between subgroup analysis of MetS associated factors were insignificant. (Figure 3)

Table 2

The association between participant demographics/characteristics and the risk of moderate to severe fatty liver
	Univariate analysis		Multivariable analysis-1		Multivariable analysis-2
Variable	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Male	2.45 (2.11–2.84)	< 0.001	2.67 (2.27–3.14)	< 0.001	1.44 (1.20–1.73)	< 0.001
Age, year	1.06 (1.05–1.08)	< 0.001	1.06 (1.05–1.08)	< 0.001	1.06 (1.05–1.08)	< 0.001
Education level, year	0.92 (0.89–0.95)	< 0.001	0.964 (0.930–0.999)	0.048	0.97 (0.93–1.00)	0.076
Intake vegetable ≥ 3 portions per day	0.96 (0.83–1.11)	0.606	1.10 (0.88–1.37)	0.393	1.08 (0.85–1.36)	0.540
Intake fruit ≥ 2 portions per day	0.89 (0.77–1.02)	0.101	0.88 (0.71–1.10)	0.258	0.85 (0.68–1.07)	0.175
Regular exercise	0.73 (0.62–0.86)	< 0.001	0.69 (0.58–0.82)	< 0.001	0.78 (0.64–0.93)	0.007
Smoking	1.67 (1.38–2.03)	< 0.001	0.98 (0.77–1.24)	0.866	0.85 (0.65–1.09)	0.198
Alcoholic drinking	1.56 (1.26–1.93)	< 0.001	1.02 (0.79–1.31)	0.888	1.05 (0.79–1.38)	0.752
Betel chewing	2.20 (1.50–3.24)	< 0.001	1.06 (0.68–1.67)	0.787	1.07 (0.66–1.74)	0.773
Number of teeth	0.978 (0.958–0.998)	0.032	1.00 (0.98–1.02)	0.917	0.99 (0.97–1.02)	0.685
Number of teeth ≥ 24	0.70 (0.52–0.95)	0.020	–	–	–	–
Using dental floss	0.93 (0.81–1.08)	0.340	0.98 (0.84–1.14)	0.756	1.004 (0.851–1.183)	0.966
Dental scaling	0.67 (0.58–0.78)	< 0.001	0.80 (0.68–0.94)	0.005	0.81 (0.69–0.96)	0.016
ALT/AST ratio
> 1.3	6.98 (5.95–8.19)	< 0.001	–	–	6.13 (5.15–7.30)	< 0.001
≤ 1.3	Reference	Reference			Reference	Reference
Abbreviation: OR, odds ratio; CI, confidence interval.

Table 3

The association between participant demographics/characteristics and the risk of metabolic syndrome
	Univariate analysis		Multivariable analysis-1		Multivariable analysis-2
Variable	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Male	1.99 (1.65–2.40)	< 0.001	1.90 (1.54–2.34)	< 0.001	1.001 (0.794–1.263)	0.993
Age, year	1.08 (1.07–1.10)	< 0.001	1.08 (1.06–1.09)	< 0.001	1.07 (1.05–1.09)	< 0.001
Education level, year	0.85 (0.82–0.88)	< 0.001	0.92 (0.89–0.97)	< 0.001	0.92 (0.88–0.96)	< 0.001
Intake vegetable ≥ 3 portions per day	1.02 (0.84–1.23)	0.865	1.21 (0.91–1.60)	0.182	1.19 (0.89–1.58)	0.252
Intake fruit ≥ 2 portions per day	0.90 (0.75–1.08)	0.257	0.91 (0.69–1.19)	0.479	0.89 (0.67–1.18)	0.405
Regular exercise	0.58 (0.47–0.72)	< 0.001	0.62 (0.49–0.79)	< 0.001	0.69 (0.54–0.88)	0.003
Smoking	2.78 (2.24–3.46)	< 0.001	1.67 (1.26–2.21)	< 0.001	1.55 (1.16–2.07)	0.003
Alcoholic drinking	1.83 (1.42–2.36)	< 0.001	0.85 (0.62–1.17)	0.310	0.83 (0.60–1.16)	0.277
Betel chewing	4.33 (2.92–6.44)	< 0.001	1.67 (1.03–2.69)	0.036	1.77 (1.07–2.94)	0.026
Number of teeth	0.95 (0.93–0.98)	< 0.001	0.99 (0.96–1.02)	0.464	0.98 (0.96–1.01)	0.241
Number of teeth ≥ 24	0.51 (0.36–0.71)	< 0.001	–	–	–	–
Using dental floss	0.94 (0.78–1.13)	0.532	0.95 (0.78–1.16)	0.631	0.97 (0.79–1.19)	0.787
Dental scaling	0.54 (0.45–0.65)	< 0.001	0.70 (0.57–0.85)	< 0.001	0.70 (0.57–0.86)	0.001
ALT/AST ratio
> 1.3	6.30 (5.10–7.78)	< 0.001	–	–	5.81 (4.61–7.34)	< 0.001
≤ 1.3	Reference	Reference			Reference	Reference
Abbreviation: OR, odds ratio; CI, confidence interval.

Our study showed that simple laboratory data, such as ALT/AST ratio and WBC count, could be simple indexes for predicting hepatosteatosis. In addition, we conducted a comprehensive analysis of educational level, lifestyle, oral hygiene, and cardiometabolic characteristics in the community study. Additionally, we compared the differences between participants with moderate-to-severe hepatosteatosis and MetS with similar pathophysiology. These findings suggest that moderate-to-severe fatty liver is associated with a cluster of adverse demographics, lifestyle, dietary habits, and health-related factors, as well as biochemical abnormalities indicative of liver dysfunction and systemic inflammation [13]. Identifying and addressing these risk factors may be crucial for the prevention and management of fatty liver disease and its associated complications.

Fatty liver disease is gaining increasing attention as a metabolic disease, and its prevalence is increasing. Recent studies have revealed that fatty liver disease, also known as chronic inflammation [14], accumulation of fats, and hepatocyte injury, plays an important role in metabolic disease development [15,16]. The outcomes of fatty liver disease can be as serious as those of liver cirrhosis and even hepatocellular carcinoma (HCC) [17] and should not be ignored. The main problem is how to evaluate the severity of the disease and how to conduct follow-ups. In our study, we enrolled 3,796 young participants from a community health check-up. The study was able to determine between moderate-to-severe and non-to-mild fatty liver disease. Moderate-to-severe fatty liver disease is more common in males who are older and have lower education levels. Thus, it is easy to infer that the disease progressed over time. As a consequence of lower education levels, the ratio of substance use, including smoking, alcohol consumption, betel chewing, and even less dental scaling, appears to increase as well. Metabolic comorbidities shared similar risk factors, including less exercise and higher waist circumference, systolic blood pressure, fasting glucose, and triglycerides, but lower levels of high–density lipoprotein (Table 1).

However, one factor that needs to be considered is that the WBC count differs greatly between moderate/severe and non/mild fatty liver disease. This may indicate that the grade of systemic inflammation was also different. WBC count is known to be correlated with the severity of sepsis and other inflammatory diseases. The two groups were all within the normal WBC range (4,500–11,000 per microliter); this difference is worth considering. Chronic low-grade inflammation with an elevated WBC count is regarded as an independent marker of fatty liver disease [18,19]. An increase in WBC count is also associated with the severity of hepatic steatosis [20]. Our study shows that AUC performs well in evaluating the independent WBC count and fatty liver or MetS compared to other complete blood counts. This result is similar to ALT. Elevated serum ALT levels are also markers of inflammation and oxidative stress in MetS [21]. The overlap of these serum markers may pose a greater risk of fatty liver progression [22]. Further investigation of systemic inflammation may help better evaluate fatty liver disease.

Serum AST and ALT are common liver enzymes used to assess liver function [23] as the release of ALT and AST from liver cells indicates hepatocellular damage or death. In our study, ALT had a more acceptable predictive value than AST in evaluating AUC for severe fatty liver disease and MetS. To make a more accurate prediction of fatty liver and MetS, we introduced the ALT/AST ratio, known as the reversal De Ritis Ratio, which was used to measure the characteristics of acute and alcoholic hepatitis. However, the ratio may change over time and with the aggressiveness of the disease due to the different half-lives of AST (18 h) and ALT (36 h) [24]. Therefore, it is best matched with chronic diseases to predict long-term complications, including fibrosis and cirrhosis in chronic hepatitis, chronic alcoholism, and fatty liver disease. In our study, there was a marked elevation in the ALT/AST ratio and cut-off value > 1.3 predicting moderate-to-severe fatty liver, which may indicate not only the severity of fatty liver but also the risk of future hepatitis to potential fibrosis. A combination of the ALT/AST ratio and advanced inflammation as an oxidative stress marker scoring system may enhance the predictive value.

Limitations

Despite the strengths of this study, it has some limitations. Detailed information regarding the medication and surgical procedure for hepatosteatosis is essential; however, we were unable to obtain it during the health check-up. A repeat laboratory examination is necessary if the WBC levels are affected by subclinical infection or starvation. The CRP and ESR are also useful laboratory measurements of inflammatory diseases [25]. However, we did not have data for our study because these measurements were not routinely obtained during health examinations. The ALT value is useful for predicting hepatic inflammation or injury; however, 25% of patients with NAFLD and 19% of patients with NASH possess normal ALT values [26]. Furthermore, large-scale and longitudinal observations are required to disentangle the correlation between the ALT/AST ratio and fatty liver.

Male sex, older age, and lifestyle factors, such as substance use and poor dental hygiene, were consistently associated with risks of MetS and fatty liver burden. ALT/AST > 1.3 might be a promising diagnostic marker for moderate-to-severe hepatosteatosis. Prevention of these metabolic disorders through early detection, lifestyle interventions, and regular health monitoring is crucial. Further research is warranted to explore additional risk factors and improve diagnostic strategies for effective prevention and management.

Abbreviation	Definition
ALT	Alanine aminotransferase
ALT/AST	Alanine transaminase/aspartate transaminase ratio
AST	Aspartate aminotransferase
AUC	Area under the curve
CI	Confidence interval
CRP	C-reactive protein
FBG	Fasting serum blood glucose
HDL-C	High-density lipoprotein-cholesterol
MetS	Metabolic syndrome
MLR	Monocyte-to-lymphocyte ratio
NAFLD	Non-alcoholic fatty liver disease
NASH	Non-alcoholic steatohepatitis
NLR	Neutrophil-to-lymphocyte ratio
OR	Odds ratio
PLR	Platelet-to-lymphocyte ratio
TG	Triglyceride
WBC	White blood cell

Ethics approval and consent to participate(Human participant protection): The Institutional Review Board approved the study (IRB NO: 202000109B0C101). Written informed consent was obtained from individual or guardian participants.

Consent for publication: Not Applicable.

Availability of data and materials: The data used to support the findings of this study are available from the corresponding author upon request.

Competing interests: The authors declare that they have no competing interests.

Funding: The authors declared they do not have anything to disclose regarding conﬂicts of interest concerning this manuscript.

Author’s Contributions: All authors contributed to the statistical analysis and writing of the study. YHL, MYC, YFW, PCW, YCT, YYH and MSL, participated in study design, data acquisition, critical review, and wrote the manuscript; YHL, MSL participated in the analysis and analysis interpretation of data; MSL, MYC collected data and contributed to study direction.

Acknowledgments: We thank Alfred Hsing‑Fen Lin for the assistance with statistics. We would like to thank the participants in this study and all staffs in the Yunlin Chang Gung Memorial Hospital for support in making this study possible.

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Risk Factors and Diagnostic Markers for Fatty Liver and Metabolic Syndrome Among Young Adults: Insights from a Community-Based Investigation

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