Background: Previous studies have suggested that bile acids (BAs) may participate in the development and/or progression of metabolic dysfunction-associated steatotic liver disease (MASLD). The present study aimed to define whether specific BA molecular species are selectively associated with MASLD development, disease severity, or geographic region. Methods: We comprehensively identified all eligible studies reporting circulating BAs in both MASLD patients and healthy controls through 30 July 2023. The pooled results were expressed as the standard mean difference (SMD) and 95% confidence interval (CI). Subgroup, sensitivity, and meta-regression analyses were performed to address heterogeneity. Results: Nineteen studies with 154,807 individuals were included. Meta-analysis results showed that total BA levels in MASLD patients were higher than those in healthy controls (SMD = 1.03, 95% CI: 0.63–1.42). When total BAs were divided into unconjugated and conjugated BAs or primary and secondary BAs, the pooled results were consistent with the overall estimates except for secondary BAs. Furthermore, we examined each individual BA and found that 9 of the 15 BAs were increased in MASLD patients, especially ursodeoxycholic acids (UDCA), taurococholic acid (TCA), chenodeoxycholic acids (CDCA), taurochenodeoxycholic acids (TCDCA), and glycocholic acids (GCA). Subgroup analysis revealed that different geographic regions or disease severities led to diverse BA profiles. Notably, TCA, taurodeoxycholic acid (TDCA), taurolithocholic acids (TLCA), and glycolithocholic acids (GLCA) showed a potential ability to differentiate metabolic dysfunction-associated steatohepatitis (MASH) (all p < 0.05). Conclusions: An altered profile of circulating BAs was shown in MASLD patients, providing potential targets for the diagnosis and treatment of MASLD.

Whether the associations between serum vitamin D (VitD) and metabolic-associated fatty liver disease (MAFLD) vary with chronic hepatitis B (CHB) infection has not been well established. This study aims to investigate the relationships between serum VitD and metabolism, liver fat content (LFC) and fibrosis among MAFLD patients with and without CHB. Consecutive subjects (healthy controls: 360, CHB: 684, MAFLD: 521, CHB with MAFLD: 206) were prospectively enrolled between January 2015 and December 2021. Anthropometric, laboratory, imaging, and histological evaluations were conducted, with LFC measured via magnetic resonance imaging-based proton density fat fraction (MRI-PDFF). Serum VitD levels were lower in MAFLD patients than in healthy controls and patients with CHB alone or overlapping with MAFLD (24.4 ± 8.1 vs. 29.0 ± 9.5 vs. 27.4 ± 9.6 vs. 26.8 ± 8.4 ng/mL respectively; p < 0.001 in one-way ANOVA test). After adjusting for confounding factors, including season, hypersensitive C-reactive protein, insulin resistance, liver stiffness measurements, sun exposure, exercise and dietary intake, multivariate linear regression analysis revealed that VitD remained significantly negatively correlated with LFC in MAFLD patients (β = −0.38, p < 0.001), but not in CHB with MAFLD patients. Moreover, quantile regression models also demonstrated that lower VitD tertiles were inversely associated with the risk of insulin resistance and moderate–severe steatosis in the MAFLD group (p for trend <0.05) but not in the MAFLD with CHB group. VitD deficiency was associated with the severity of metabolic abnormalities and steatosis independent of lifestyle factors in MAFLD-alone subjects but not in MAFLD with CHB subjects.

Background/Objectives: Weight loss is the primary therapy for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the proportion and factors influencing therapeutic changes in the liver condition contrary to weight loss remain unclear. Methods: This observational cohort study spanned between January 2015 and January 2024, with a 48-week lifestyle modification until January 2025. The liver fat content (LFC) determined using MRI-PDFF and liver stiffness measurement (LSM) via 2D-SWE were assessed at baseline and 48 weeks. The weight loss target (WLT) was determined as a reduction of ≥3% in body weight for lean/normal-weight patients and ≥5% for patients who were overweight/obese. Results: Overall, 397 patients with MASLD (30.5% achieving WLT) were included. For participants with WLT, 24.8% presented MRI-PDFF non-response, which was associated with moderate–vigorous physical activity (MVPA) ≥ 150 min/week, indicating a lower likelihood of non-response. Alanine aminotransferase (ALT) non-response occurred in 29.6% of patients and was linked to changes in LFC (ΔLFC, calculated as the baseline minus week 48). LSM non-response was observed in 48.2%, with high free fatty acid (FFA) levels identified as a risk factor. Among individuals without WLT, 29.0% demonstrated an MRI-PDFF response that correlated with greater reductions in low-density lipoprotein cholesterol; 39.4% exhibited an ALT response, which was associated with more significant reductions in LFC. The LSM response was 37.8%, also correlating with a reduction in LFC. Conclusions: Our results identified that MVPA, baseline steatosis degree, FFA, and their responses served as significant markers for treatment response contrary to weight loss in MASLD.

Background: The 1-h post-load plasma glucose was proposed to replace the current OGTT criteria for diagnosing prediabetes/diabetes. However, it remains unclear whether it is superior in identifying progressive metabolic dysfunction-associated steatotic liver disease (MASLD), and thus we aimed to clarify this issue. Methods: Consecutive Asian participants (non-MASLD, n = 1049; MASLD, n = 1165) were retrospectively enrolled between June 2012 and June 2024. CT was used to quantify liver steatosis, while the serum liver fibrotic marker was used to evaluate liver fibrosis. Results: Compared with those with normal levels of both 1-h post-glucose (1hPG) and 2-h post-glucose (2hPG), patients with MASLD showed a significant positive association between elevated 1hPG levels and moderate to severe liver steatosis (odds ratio [OR] = 2.19, 95% confidence interval [CI]: 1.13–4.25, p = 0.02]. Elevated levels of both 1hPG and 2hPG were associated with an increased risk of liver injury (OR = 2.03, 95% CI: 1.44–2.86, p < 0.001). Elevated 2hPG levels with or without elevated 1hPG levels were associated with liver fibrosis (OR = 1.99, 95% CI: 1.15–3.45, p < 0.001; OR = 2.72, 95% CI: 1.79–4.11, p < 0.001, respectively). Additionally, either 1hPG or 2hPG levels were associated with atherosclerosis, revealing significant dose-dependent associations between glucose status and atherosclerosis risk (OR = 2.77, 95% CI: 1.55–4.96, p < 0.001 for elevated 1hPG; OR = 2.98, 95% CI = 1.54–5.78, p = 0.001 for elevated 2hPG; OR = 2.41, 95% CI = 1.38–4.21, p = 0.001 for elevated levels of both 1hPG and 2hPG). The areas under the ROC for predicting steatosis, liver injury, liver fibrosis, and atherosclerosis were 0.64, 0.58, 0.58, and 0.64 for elevated 1hPG (all p < 0.05) and 0.50, 0.60, 0.56, and 0.62 for elevated 2hPG (all p < 0.05), respectively. Conclusions: These findings underscore the necessity for clinicians to acknowledge that the screening and management of MALSD requires the monitoring of 1hPG levels.

Ling Luo, Congxiang Shao, Tingfeng Wu, Long Teng, Jiaming Lai, Shuyu Zhuo, Zhi Dong, Wei Wang, Junzhao Ye, Bihui Zhong. J Obes Metab Syndr -0001;0:0-. https://doi.org/10.7570/jomes25076