J Obes Metab Syndr 2023; 32(3): 279-283
Published online September 30, 2023 https://doi.org/10.7570/jomes23035
Copyright © Korean Society for the Study of Obesity.
1The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul; Departments of 2Internal Medicine, 3Outpatient Nursing, 4Healthcare, Armed Forces Goyang Hospital, Goyang, Korea
Department of Internal Medicine, Armed Forces Goyang Hospital, 215 Hyeeum-ro, Deogyang-gu, Goyang 10267, Korea
The first two authors contributed equally to this study.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Sarcopenia has been associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the correlation between liver fibrosis and muscle mass in young adults with NAFLD.
Methods: We conducted a retrospective review of 88 Korean soldiers <35 years of age who underwent bioelectrical impedance analysis and liver stiffness measurements. A FibroScan-aspartate aminotransferase score >0.35 was used to determine the presence of liver fibrosis.
Results: Among the 88 patients, 38 were classified as having significant fibrosis. In the univariate analysis, muscle mass percentage (MMP), muscle-to-fat ratio (MFR), waist-to-hip ratio (WHR), body mass index, impaired fasting glucose or diabetes mellitus, and alanine transaminase (ALT) level were all significantly associated with fibrosis (P<0.001). After adjusting for ALT level, height, and age, MMP and WHR were associated with fibrosis.
Conclusion: In young adults, MMP and MFR were significantly associated with hepatic fibrosis.
Keywords: Non-alcoholic fatty liver disease, Sarcopenia, Liver fibrosis, Muscle mass, Young adult
A recent study using a Swedish nationwide cohort demonstrated that patients with NAFLD and fibrosis have a 5.88-fold higher mortality rate than do patients without NAFLD or fibrosis.6,7 These findings highlight the importance of identifying patients with liver fibrosis, particularly young patients.
Sarcopenia, which is associated with increased risk of NAFLD and fibrosis, has been extensively studied over the last decade.8-10 Although it is widely accepted that sarcopenia is a key factor in the management of NAFLD, it is unclear whether sarcopenia causes NAFLD, or
Since the relationship between NAFLD and sarcopenia has not been studied in younger populations, this study sought to elucidate the correlation between liver fibrosis and muscle mass in young adults with NAFLD. The correlation was evaluated using total muscle mass adjusted for body weight (muscle mass percentage [MMP]) and muscle-to-fat ratio (MFR).
This study was approved by the Institutional Review Board of the Korean Armed Forces Medical Command (AFMC-202212-HR-061-01) and was performed in accordance with the Declaration of Helsinki. We retrospectively reviewed the medical records of patients diagnosed with NAFLD by abdominal ultrasonography between July 2022 and September 2022. Patients between 18 and 35 years of age were included. Patients with transaminase level >300 U/L were excluded because of the possibility of transient elastography (TE) overestimation. Informed consent was not required because this research was retrospective.
Liver stiffness was measured by vibration-controlled TE using the FibroScan 502 (Echosens). Muscle mass, fat mass, body mass index (BMI), and waist-to-hip ratio (WHR) were measured using a bioelectrical impedance analyzer (T-Scan Plus; Jawon Medical). Additionally, we used the controlled attenuation parameter scores, measured by FibroScan 502, to identify hepatic steatosis.
Significant fibrosis (F2 or higher in the META-analysis of histological data in VIRal hepatitis [METAVIR] scoring system) was determined using the FibroScan-aspartate aminotransferase (FAST) score and was considered absent with a score <0.35.11 To reduce bias, the following two additional cut-offs were adopted to define significant fibrosis and reveal its associated factors: FAST score ≥0.67 and TE ≥7.0 kPa.12 We applied the cut-off value proposed by Karlas et al.13 to classify the degree of steatosis. Severe obesity was defined as BMI ≥30 kg/m2, while nonsevere obesity was defined as BMI <30 kg/m2.
All statistical analyses were performed using R statistical software version 4.0.3 (R Foundation Inc.). Detailed statistical methods are described in the Supplementary Methods.
The total number of participants was 88, among whom 38 had a FAST score >0.35, which was classified as significant fibrosis (Table 1). Differences in the MMP, WHR, BMI, and MFR between the two groups were significant (
In the univariate analysis, MMP, MFR, WHR, BMI, impaired fasting glucose (IFG)/diabetes mellitus (DM), and alanine transaminase (ALT) level were all associated with significant fibrosis (Table 2). Two models were established in the multivariate analysis. Age and height were adjusted as covariates for model 1, whereas ALT level was added as an adjustment for model 2. All included variables in model 1 were associated with significant fibrosis. In contrast, only MMP, WHR, and IFG/DM were associated with significant fibrosis in model 2 (MMP: odds ratio [OR] 0.685,
Subgroup analyses were performed for non-severely obese and severely obese patients with NAFLD (Supplementary Table 3). After adjusting for height and age as covariates, MMP, MFR, WHR, IFG/DM, and ALT were significantly associated with fibrosis in the obese NAFLD subgroup (MMP: OR 0.705,
In this study, the MMP and MFR were significantly correlated with fibrosis, as were WHR and BMI. Both MMP and MFR were associated with significant fibrosis in nonsevere obese patients with NAFLD.
Another study similarly found that NAFLD seems to share diverse mechanisms with sarcopenic obesity, and the correlation between them is widely accepted.9 The prevalence of NAFLD and the proportion of cirrhosis caused by NAFLD are both increasing.14 Considering that NAFLD at younger ages is related to increased mortality,7 the modifiable factors of NAFLD, such as the MFR, need to be identified.
To the best of our knowledge, this is the first study revealing the relationship between muscle mass and liver fibrosis in young adults. Due to the lack of consideration for sarcopenia in younger groups, BMI has been considered the only correctable factor for young patients with NAFLD. In this study, we suggest that not only fat mass, but also muscle mass needs to be corrected to ameliorate fibrotic changes in NAFLD. In addition, the relationship between liver fibrosis, MFR, and MMP was validated in the nonsevere obese group, emphasizing a role of these possible correctable factors in NAFLD in young patients.
This study has several limitations, such as the small number of patients enrolled. Also, technical limitations of the bioelectrical impedance analyzer prevented us from calculating the skeletal muscle mass.
In conclusion, our findings indicate that MMP and MFR are correlated with liver fibrosis in (both obese and non-obese) young patients with NAFLD. Further analysis, including biopsy-proven data and skeletal muscle mass, will better explain this correlation.
The authors declare no conflict of interest.
This study was supported by the Korean Military Medical Research Project, which is funded by the Ministry of National Defense (grant number 2023-KMMRP-004).
Study concept and design: JL and SN; acquisition of data: all authors; analysis and interpretation of data: JL; drafting of the manuscript: JL and SN; critical revision of the manuscript: all authors; statistical analysis: JL and SN; obtained funding: JL; administrative, technical, or material support: JL and SN; and study supervision: JL and SHB.
Baseline patient characteristics
|Characteristic||Non-fibrosis (n=50)||Significant fibrosis (n=38)||Total (n=88)|
|Age (yr)||21.0 (20.0–22.0)||20.0 (20.0–21.0)||21.0 (20.0–21.0)||0.155|
|Male sex||50 (100)||38 (100)||88 (100)||NA|
|Muscle mass (kg)||56.7 ±7.0||64.3 ±6.8||59.9 ±7.9||< 0.001|
|Fat mass (kg)||18.3 ±7.2||29.2 ±6.4||23.0 ±8.8||< 0.001|
|MFR||3.13 (2.42–4.39)||2.23 (1.97–2.52)||2.61 (2.14–3.49)||< 0.001|
|MMP (%)||72.2 ±5.5||65.0 ±4.1||69.1 ±6.1||< 0.001|
|WHR (%)||82.1 ±6.2||88.4 ±5.2||85.0 ±5.9||< 0.001|
|BMI (kg/m2)||26.1 ±3.8||32.0 ±3.6||28.7 ±4.7||< 0.001|
|IFG/DM||12 (24.0)||30 (78.9)||42 (47.7)||< 0.001|
|HTN||12 (24.0)||10 (26.3)||22 (25.0)||1.000|
|Dyslipidemia||13 (26.0)||12 (31.6)||25 (28.4)||0.737|
|WBC (1,000/μL)||6,254.2 ±1,627.1||7,513.7 ±2,252.4||6,798.1 ±2,010.5||0.003|
|PLT (109/L)||255.4 ±46.4||285.4 ±46.6||268.4 ±48.6||0.004|
|TB (mg/dL)||0.9 (0.7–1.0)||0.9 (0.7–1.2)||0.9 (0.7–1.1)||0.843|
|AST (IU/L)||22.5 (18.6–27.7)||61.9 (50.3–91.5)||32.0 (21.8–54.8)||< 0.001|
|ALT (IU/L)||27.0 (17.5–52.3)||141.0 (100.3–209.5)||65.5 (24.0–131.5)||< 0.001|
|GGT (IU/L)||24.5 (18.0–31.5)||61.5 (45.0–84.8)||33.5 (22.0–64.3)||< 0.001|
|Albumin (mg/dL)||5.0 ±0.2||5.1 ±0.2||5.1 ±0.2||0.284|
|INR||1.0 ±0.1||1.0 ±0.0||1.0 ±0.1||0.060|
|Cr (mg/dL)||0.88 (0.82–0.95)||0.88 (0.80–0.94)||0.88 (0.82–0.94)||0.468|
|CAP (dB/m)||250.5 (220.5–290.8)||332.0 (304.8–347.8)||297.0 (235.8–328.3)||< 0.001|
|LSM (kPa)||4.3 (3.9–5.7)||7.4 (6.0–8.6)||5.8 (4.2–7.2)||< 0.001|
Values are presented as median (interquartile range), number (%), or mean±standard deviation.
MFR, muscle mass-to-fat mass ratio; MMP, muscle mass percentage; WHR, waist-to-hip ratio; BMI, body mass index; IFG, impaired fasting glucose; DM, diabetes mellitus; HTN, hypertension; WBC, white blood cell; PLT, platelet; TB, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; INR, international normalized ratio; Cr, creatinine; CAP, controlled attenuation parameter; LSM, liver stiffness measurement.
Factors associated with significant fibrosis
|Variable||r||Univariate analysis||Model 1||Model 2|
|Crude OR (95% CI)||Adjusted OR (95% CI)||Adjusted OR (95% CI)|
|MMP||–0.58||0.743 (0.644–0.833)||< 0.001||0.714 (0.606–0.812)||< 0.001||0.685 (0.370–0.999)||0.050|
|MFR||–0.50||0.152 (0.059–0.388)||< 0.001||0.129 (0.048–0.351)||< 0.001||0.105 (0.008–1.373)||0.086|
|WHR||0.52||1.290 (1.158–1.472)||< 0.001||1.362 (1.205–1.587)||< 0.001||1.525 (1.002–2.322)||0.049|
|BMI (kg/m2)||0.62||1.496 (1.289–2.806)||< 0.001||-||-||-||-|
|BMI ≥ 30 kg/m2||0.49||8.867 (3.358–23.410)||< 0.001||-||-||-||-|
|WBC > 7,000/μL||0.25||2.304 (0.945–5.759)||0.069||2.661 (1.044–7.091)||0.044||0.949 (0.096–9.394)||0.964|
|IFG/DM||0.54||11.875 (4.495–34.678)||< 0.001||11.916 (4.457–35.338)||< 0.001||499.2 (1.67–1.49 × 105)||0.032|
|ALT||0.72||1.110 (1.106–1.201)||< 0.001||1.126 (1.066–1.247)||0.002||-||-|
Model 1 considered height and age as covariates. Model 2 considered height, age, and ALT as covariates.
OR, odds ratio; CI, confidence interval; MMP, muscle mass percentage; MFR, muscle mass-to-fat mass ratio; WHR, waist-to-hip ratio; BMI, body mass index; WBC, white blood cell; IFG, impaired fasting glucose; DM, diabetes mellitus; ALT, alanine aminotransferase.