Association Between Mental Health and Metabolic Dysfunction–Associated Fatty Liver Disease

By Ji Hyeon Park¹, Yoo Jeong Lee², In Cheol Hwang³, Hong Yup Ahn⁴

Affiliations

1. Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
2. Palliative Care Centre and Department of Family Medicine, Korea University Guro Hospital, Seoul, South Korea
3. Department of Family Medicine, Gil Medical Centre, Gachon University College of Medicine, Incheon, South Korea
4. Department of Statistics, Dongguk University, Seoul, South Korea

doi: 10.29271/jcpsp.2025.12.1633

ABSTRACT
Depression has recently been identified as a potential predisposing factor for metabolic dysfunction–associated fatty liver disease (MAFLD) among adults in the US. This cross-sectional, nationwide study examined the association between mental health and MAFLD in Korean adults. Mental state was addressed using a question for suicidal ideation and depressive mood, and MAFLD was assessed according to the criteria established by an international expert panel. A stepwise multivariate logistic regression analysis revealed that MAFLD was significantly more common in men with suicidal ideation and in women with depressive mood compared with their non- suicidal and non-depressed counterparts, respectively. These results warrant mental health screening among patients with MAFLD.

Key Words: Depression, Metabolic diseases, Fatty liver disease, Suicidal ideation.

Metabolic dysfunction–associated with fatty liver disease (MAFLD) is emerging as an attractive substitute for non-alcoholic fatty liver disease (NAFLD) because it reflects the presence of metabolic abnormalities in the setting of hepatic steatosis.¹ As there is not yet an approved medication for MAFLD, a better understanding of its reversible risk factors is needed to reduce the disease burden and healthcare costs. While depression has recently been identified as a potential predisposing factor for MAFLD among adults in the US based on previous observations linking depression to NAFLD,² a recent Italian study fails to identify the significant association between depression and MAFLD.³ Given the differences in mental health status across cultural contexts, this study examined the association between two aspects of mental health—depression and suicidality—and MAFLD in Korean adults.

Data were obtained from three years of the Korea National Health and Nutrition Examination Survey that included measurements of suicidal ideation in adults (2015, 2017, and 2019). Among 19,069 participants aged 19 years and older, 2,100 were excluded due to missing data on suicidal ideation or MAFLD. After further excluding participants with missing data for the covariates, 16,018 individuals were included in the final analysis.

According to expert panel criteria,¹ MAFLD was defined as the presence of hepatic steatosis with one or more of the following: overweight, type II diabetes mellitus, or at least two metabolic abnormalities. These abnormalities included central obesity, high blood pressure or specific medicine treatment, prediabetes, low high-density lipoprotein (HDL) cholesterol or specific medicine treatment, hypertriglyceridaemia or specific medicine treatment, increased homeostasis model assessment of insulin resistance score (HOMA-IR ≥2.5), or increased high-sensitivity C-reactive protein (hc-CRP >2 mg/dL). Depression was assessed using a single question: ‘‘Have you ever felt sadness or despair continuously for two weeks during the past year?’’ Suicidal ideation was evaluated using the question: ‘‘Have you ever thought about suicide during the recent 12 months?’’

Covariates included demographic characteristics (age, gender, education level, and household income), habits (smoking, drinking, and exercise), and depression. Problem drinking was defined as consuming ≥7 drinks (men) or 5 drinks (women) in one sitting, more than 2 days/week. Regular exercise was defined as a moderate activity ≥5 times per week or a vigorous activity ≥3 times per week.

Subject characteristics were analysed according to MAFLD through a t-test or Chi-square test. A stepwise multivariate logistic model was use to identify factors associated with MAFLD. STATA SE 9.2 (Stata Corp., TX, USA) was used for statistical analysis, and a p-value of <0.05 was regarded as statistically significant.

Approximately 21% of participants had MAFLD. The MAFLD group was more likely to be younger, to engage in healthy habits, and to have poorer mental health (Table I).

Table I: Characteristics of participants with MAFLD.

Parameters	MAFLD
	Absent (n = 12,546)	Present (n = 3,472)	p-values
Age (years)	51.5 ± 16.9	50.1 ± 15.5	<0.001
Gender
Male	5,303 (42.3)	1,791 (51.6)	<0.001
Female	7,243 (57.7)	1,681 (48.4)
Income level
Quartile 3, 4	7,159 (57.1)	1,963 (56.5)	0.581
Quartile 1, 2	5,387 (42.9)	1,509 (43.5)
Education level
High school or beyond	8,804 (70.2)	2,408 (69.4)	0.351
Middle school or less	3,742 (29.8)	1,064 (30.7)
Health-related habits
Current smoking	2,068 (16.5)	728 (21.0)	<0.001
Problem drinking	4,244 (33.8)	1,194 (34.4)	0.536
Regular exercise	5,666 (45.2)	1,478 (42.6)	0.007
Mental health
Depressive mood	1,443 (11.5)	453 (13.12)	0.013
Suicidal ideation	589 (4.7)	201 (5.8)	0.008
Data are presented as mean ± standard deviation or number (percentage). p-values were determined using the t-test or Chi-square test.

Table II: Factors associated with MAFLD.

Parameters	Men (n = 7,094)		Women (n = 8,924)
	ORa (95% CI)	p-values	ORa (95% CI)	p-values
Age (per 1-year decrease)	1.02 (1.02–1.03)	<0.001
Gender (men vs. women)
Low-income level			1.18 (1.05–1.33)	0.005
Low education level	0.74 (0.63–0.88)	<0.001	1.68 (1.49–1.89)	<0.001
Current smoking status
Problem drinking	0.86 (0.77–0.97)	0.010
Non-regular exercise	1.25 (1.12–1.40)	<0.001	1.14 (1.02–1.28)	0.018
Depression			1.16 (1.00–1.35)	0.044
Suicidal ideation	1.42 (1.09–1.86)	0.010
OR: Odds ratio; CI: Confidence interval. The factors used for diagnosing MAFLD were not included in the analysis. aThe stepwise multivariate logistic regression analysis was used with adjustment for demographics (age, gender as appropriate, income level, education level), habits (smoking, drinking, and exercise), and mental status (depressive mood and suicidal ideation).

Table II shows the factors associated with MAFLD by gender. Physical inactivity showed a similar effect in both males and females. Depression was associated with MAFLD among women, whereas suicidal ideation was associated with MAFLD among men. Specifically, men with suicidal ideation were 1.42 times more likely to have MAFLD compared with those without suicidal ideation.

This study examined the association between mental health—especially suicidal ideation and depression—and MAFLD among Korean adults. A similar Korean study⁴ reported no association between mental health and MAFLD; however, the study focused on health-related quality of life and did not perform a gender-specific analysis despite the distinct features of NAFLD by gender. Several mechanisms linked depression to fatty liver, including chronic inflam-mation, increased activity of monoamine oxidase-A, and the hypothalamic–pituitary–adrenal axis dysregulation.⁵ Clinical evidence also elucidated the associations of depressive mood with fatty liver via shared risk factors and poor lifestyle modifications.⁶

In this study, the associations differed by gender: MAFLD was more common in men with suicidal ideation and women with depressive mood compared with their non-suicidal and non-depressed counterparts, respectively. Gender-specific findings in this study could be the result of sexual dimorphism of suicidal behaviours. Although suicidal ideation and suicide attempt are more prevalent in women, suicide completion is more common in men. This suggests that men who attempt suicide may have a stronger desire to succeed, leading to more fatal behaviours and a complete higher rate of suicide than women. Thus, suicidal ideation among men is likely to be more serious and risky.

This study has several limitations. First, the cross-sectional study design prevented the ability to establish temporal causality. Second, the assessments of mental health depended on single-item questions rather than structured tests (e.g., the Beck Depression Inventory or Patient Health Questionnaire-9 for depression, and the Ask Suicide-Screening Questions for suicide). However, such single-item measurements have been used in several epidemiologic studies, with validity and reliability. Third, residual confounding factors, such as diet,⁶ may partly explain the association. Therefore, prospective cohort studies or Mendelian randomisation studies are needed to strengthen the evidence. Despite these limitations, this study is the first to identify gender differences in the relationship between mental health and MAFLD. The results suggest that suitable mental health screening in patients with MAFLD may facilitate early identification of low mood and help prevent further progression of MAFLD.

FUNDING:
This work was supported by Gachon University Gil Medical Centre (Grant No. FRD2021-14).

ETHICAL APPROVAL:
Ethical approval was obtained from the Institutional Review Board of Gachon University Gil Medical Centre (IRB No. GFIRB2022-099) and the study followed the guidelines set forth in the Declaration of Helsinki.

PATIENTS’ CONSENT:
Informed consent was obtained from the participants.

COMPETING INTEREST:
The authors declared no conflict of interest.

AUTHORS’ CONTRIBUTION:
JHP, YJL: Interpretation and manuscript preparation.
ICH: Conceptualisation, methodology, manuscript review, and editing.
HYA: Formal analysis and interpretation.
All authors have approved the final version of the manuscript to be published. Drs. Park and Lee contributed equally to this work.

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