An Optimized Strategy Based on Conventional Ultrasound for Diagnosing Metabolic Dysfunction-Associated Steatotic Liver Disease.

The inherent drawbacks of the conventional B-mode ultrasound for metabolic dysfunction-associated steatotic liver disease (MASLD) are poorly understood. We aimed to investigate the impact factors and optimize the screening performance of ultrasound in MASLD. In a prospective pilot cohort recruited from July 2020 to January 2022, subjects who had undergone magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), ultrasound, and laboratory test-based assessments were included in the deprivation cohort. A validation cohort including 426 patients with liver histologic assessments from five medical centers in South China was also recruited. A total of 1489 Chinese subjects were enrolled in the deprivation cohort, and ultrasound misdiagnosed 62.2% of the non-MASLD patients and failed to detect 6.1% of the MASLD patients. The number of metabolic dysfunction components and the alanine aminotransferase (ALT) level were associated with a missed diagnosis by ultrasound (OR = 0.67, 95% CI 0.55-0.82 p < 0.001; OR = 0.50, 95% CI 0.31-0.79, p = 0.003, respectively). Compared with ultrasound alone, the new strategy based on ultrasound, in combination with measurements of the number of metabolic dysfunction components and ALT and uric acid levels, significantly improved the AUROC both in the research cohort and the validation cohort (0.66 vs. 0.84, 0.83 vs. 0.92, respectively). The number of metabolic dysfunction components and ALT and uric acid levels improved the screening efficacy of ultrasound for MASLD.

Alterations in Circulating Bile Acids in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis.

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.

Treatment of obesity and metabolic-associated fatty liver disease with a diet or orlistat: A randomized controlled trial.

BACKGROUND: Losing weight by lifestyle interventions is the first-line treatment for metabolic-associated fatty liver disease (MAFLD) but is limited by low compliance. OBJECTIVES: This study aimed to compare the effects of orlistat or an experimental high-protein/lower-carbohydrate diet with a control diet in Asian patients with obesity and MAFLD. METHODS: A total of 118 Asian patients with obesity and MAFLD confirmed with MRI-based proton density fat fraction with Dixon sequence were enrolled and allocated to the control group, the orlistat group, or the experimental diet group for 24 wk. The primary endpoint was the relative change in liver fat content (LFC) assessed by MRI-based proton density fat fraction. RESULTS: A total of 118 subjects with obesity and MAFLD were randomly assigned to the control group (n = 39), the orlistat group (n = 40), or the experimental diet group (n = 39). All 3 groups demonstrated improvement in liver steatosis at wk 24. The absolute decrease in LFC in the orlistat group was 9.1% and 5.4% in the experimental diet group, both significantly higher than that in the control group (P < 0.05). The relative reduction in LFC was 30.2% in the experimental diet group, which was significantly higher than the 12.2% observed in the control group (P = 0.01). CONCLUSIONS: Orlistat and the experimental diet group reduced liver steatosis compared to the control group. This trial was registered at Chinese Clinical Trial Registry (ChiCTR-1900027172). http://www.chictr.org.cn.

Age patterns of nonalcoholic fatty liver disease incidence: heterogeneous associations with metabolic changes.

BACKGROUND: As the nonalcoholic fatty liver disease (NAFLD) epidemic matures, understanding how metabolic changes in NAFLD development vary over the age distribution is important to guide precise prevention. We aimed to clarify metabolic trends in age-specific NAFLD incidence. METHODS: We conducted a 4-year longitudinal retrospective cohort study enrolling 10,240 consecutive healthy individuals who received annual physical examination during 2012-2019. Baseline and dynamic changes in metabolism and hepatic steatosis determined with ultrasound were collected and analyzed stratified by age into the following groups: 20-34, 35-49, 50-64, and over 65 years. RESULTS: Overall, 1701 incident NAFLD participants (16.6%) were identified. Adjusted Cox regression analysis showed that the baseline and increased body mass index were the main risk factors for NAFLD in people ≤ 65 years old. Baseline high-density lipoprotein (HR = 0.56; 95% CI 0.39-0.78) was a protective factor for newly onset NAFLD in the 50-to-64-year-old group, while baseline SBP (HR = 1.03; 95% CI 1.01-1.05), baseline uric acid (HR = 1.04; 95% CI 1.01-1.07), triglyceride increase (HR = 4.76; 95% CI 3.69-6.14), fasting blood glucose increase (HR = 1.32; 95% CI 1.06-1.65) were independently associated with incident NAFLD in over-65-year-old group. CONCLUSIONS: NAFLD incidence attributable to potentially metabolic risk factors varied substantially across age groups in a cohort of Chinese people. The adoption of age targeted metabolic prevention strategies might reduce the burden of NAFLD.