Non-invasive Scores and Serum Biomarkers for Fatty Liver in the Era of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Comprehensive Review From NAFLD to MAFLD and MASLD.

PURPOSE OF REVIEW: The prevalence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide, making it the leading cause of liver related morbidity and mortality. Currently, liver biopsy is the gold standard for assessing individuals with steatohepatitis and fibrosis. However, its invasiveness, sampling variability, and impracticality for large-scale screening has driven the search for non-invasive methods for early diagnosis and staging. In this review, we comprehensively summarise the evidence on the diagnostic performance and limitations of existing non-invasive serum biomarkers and scores in the diagnosis and evaluation of steatosis, steatohepatitis, and fibrosis. RECENT FINDINGS: Several non-invasive serum biomarkers and scores have been developed over the last decade, although none has successfully been able to replace liver biopsy. The introduction of new NAFLD terminology, namely metabolic dysfunction-associated fatty liver disease (MAFLD) and more recently metabolic dysfunction-associated steatotic liver disease (MASLD), has initiated a debate on the interchangeability of these terminologies. Indeed, there is a need for more research on the variability of the performance of non-invasive serum biomarkers and scores across the diagnostic entities of NAFLD, MAFLD and MASLD. There remains a significant need for finding valid and reliable non-invasive methods for early diagnosis and assessment of steatohepatitis and fibrosis to facilitate prompt risk stratification and management to prevent disease progression and complications. Further exploration of the landscape of MASLD under the newly defined disease subtypes is warranted, with the need for more robust evidence to support the use of commonly used serum scores against the new MASLD criteria and validation of previously developed scores.

Non-alcoholic fatty liver disease and coexisting depression, anxiety and/or stress in adults: a systematic review and meta-analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, affecting 25-30% of the general population globally. The condition is even more prevalent in individuals with obesity and is frequently linked to the metabolic syndrome. Given the known associations between the metabolic syndrome and common mental health issues, it is likely that such a relationship also exists between NAFLD and mental health problems. However, studies in this field remain limited. Accordingly, the aim of this systematic review and meta-analysis was to explore the prevalence of one or more common mental health conditions (i.e., depression, anxiety, and/or stress) in adults with NAFLD. Methods: PubMed, EBSCOhost, ProQuest, Ovid, Web of Science, and Scopus were searched in order to identify studies reporting the prevalence of depression, anxiety, and/or stress among adults with NAFLD. A random-effects model was utilized to calculate the pooled prevalence and confidence intervals for depression, anxiety and stress. Results: In total, 31 studies were eligible for inclusion, involving 2,126,593 adults with NAFLD. Meta-analyses yielded a pooled prevalence of 26.3% (95% CI: 19.2 to 34) for depression, 37.2% (95% CI: 21.6 to 54.3%) for anxiety, and 51.4% (95% CI: 5.5 to 95.8%) for stress among adults with NAFLD. Conclusion: The present findings suggest a high prevalence of mental health morbidity among adults with NAFLD. Given the related public health impact, this finding should prompt further research to investigate such associations and elucidate potential associations between NAFLD and mental health morbidity, exploring potential shared underlying pathophysiologic mechanisms. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021288934.

Changes in lumbar muscle diffusion tensor indices with age.

Objective: To investigate differences in diffusion tensor imaging (DTI) parameters and proton density fat fraction (PDFF) in the spinal muscles of younger and older adult males. Methods: Twelve younger (19-30 years) and 12 older (61-81years) healthy, physically active male participants underwent T1W, T2W, Dixon and DTI of the lumbar spine. The eigenvalues (λ1, λ2, and λ3), fractional anisotropy (FA), and mean diffusivity (MD) from the DTI together with the PDFF were determined in the multifidus, medial and lateral erector spinae (ESmed, ESlat), and quadratus lumborum (QL) muscles. A two-way ANOVA was used to investigate differences with age and muscle and t-tests for differences in individual muscles with age. Results: The ANOVA gave significant differences with age for all DTI parameters and the PDFF (P < .01) and with muscle (P < .01) for all DTI parameters except for λ1 and for the PDFF. The mean of the eigenvalues and MD were lower and the FA higher in the older age group with differences reaching statistical significance for all DTI measures for ESlat and QL (P < .01) but only in ESmed for λ3 and MD (P < .05). Conclusions: Differences in DTI parameters of muscle with age result from changes in both in the intra- and extra-cellular space and cannot be uniquely explained in terms of fibre length and diameter. Advances in knowledge: Previous studies looking at age have used small groups with uneven age spacing. Our study uses two well defined and separated age groups.

Age-Related Differences in Trunk Kinematics and Interplanar Decoupling with the Pelvis during Gait in Healthy Older versus Younger Men.

This study investigated age-related differences in trunk kinematics during walking in healthy men. Secondary aims were to investigate the covarying effects of physical activity (PA) and lumbar paravertebral muscle (LPM) morphology on trunk kinematics, and the effect of age on interplanar coupling between the trunk and pelvis. Three-dimensional (3D) trunk and pelvis motion data were obtained for 12 older (67.3 ± 6.0 years) and 12 younger (24.7 ± 3.1 years) healthy men during walking at a self-selected speed along a 10 m walkway. Phase-specific differences were observed in the coronal and transverse planes, with midstance and swing phases highlighted as instances when trunk and pelvic kinematics differed significantly (p < 0.05) between the younger group and older group. Controlling for age, fewer significant positive correlations were revealed between trunk and pelvic ranges and planes of motion. LPM morphology and PA were not significant covariates of age-related differences in trunk kinematics. Age-related differences in trunk kinematics were most apparent in the coronal and transverse planes. The results further indicate ageing causes an uncoupling of interplanar upper body movements during gait. These findings provide important information for rehabilitation programmes in older adults designed to improve trunk motion, as well as enable identification of higher-risk movement patterns related to falling.

Effects of resistance exercise and whey protein supplementation on skeletal muscle strength, mass, physical function, and hormonal and inflammatory biomarkers in healthy active older men: a randomised, double-blind, placebo-controlled trial.

PURPOSE: To determine the individual and combined effects of 12 weeks of resistance exercise (RE) and whey protein supplementation on skeletal muscle strength (primary outcome), mass and physical function, and hormonal and inflammatory biomarkers in older adults. METHODS: Thirty-six healthy older men [(mean±SE) age: 67±1 y; BMI: 25.5±0.4 kg/m2] were randomised to either control (CON; n=9), whey protein (PRO; n=9), RE+control (EX+CON; n=9), or RE+whey protein (EX+PRO; n=9) in a double-blinded fashion. Whole-body RE (2 sets of 8 repetitions and 1 set to volitional failure at 80% 1RM) was performed twice weekly. Supplements (PRO, 25 g whey protein isolate; CON, 23.75 g maltodextrin) were consumed twice daily. RESULTS: EX+CON and EX+PRO increased leg extension (+19±3 kg and +20±3 kg, respectively) and leg press 1RM (+27±3 kg and +39±2 kg, respectively) greater than the CON and PRO groups (P<0.001, Cohen's d=1.50-1.90). RE (EX+CON and EX+PRO groups pooled) also increased fat-free mass (FFM) (+0.9±0.3 kg) and 6-min walk test distance (+21±5 m) and decreased fat mass (-0.4±0.4 kg), and interleukin-6 (-1.0±0.4 pg/mL) and tumor necrosis factor-alpha concentration (-0.7±0.3 pg/mL) greater than non-exercise (CON and PRO groups pooled; P<0.05, Cohen's f=0.37-0.45). Whey protein supplementation (PRO and EX+PRO groups pooled) increased 4-m gait speed greater than control (CON and EX+CON groups pooled) (+0.08±0.03 m/s; P=0.007, f=0.51). CONCLUSION: RE increased muscle strength, FFM and physical function, and decreased markers of systemic inflammation in healthy active older men. Whey protein supplementation alone increased gait speed. No synergistic effects were observed. This study was registered at clinicaltrials.gov as NCT03299972.

Age-related degeneration of lumbar muscle morphology in healthy younger versus older men.

AIM: The aim of this study was to evaluate age-related changes in lumbar paravertebral muscle (LPM) morphology in healthy younger and older adult men. METHODS: T2-weighted axial MRI of the lumbar spine were obtained for 12 healthy older (67.3 ± 6.0 years) and younger (24.7 ± 3.1 years) men. Normalised muscle volume (NMV) and muscle fat infiltrate (MFI) were determined bilaterally for the psoas (PS), quadratus lumborum (QL), erector spinae (ES) and multifidus (MF). MANOVA was used to compare NMV and MFI between age groups. Follow-up ANOVA compared NMV and MFI for each muscle between age groups, with physical activity (PA) as a covariate. Stepwise regression was used to explore the association between muscle morphology. RESULTS: NMV of the ES and QL were significantly lower in the older group (OG) (p = 0.040 and p < 0.001, respectively). MFI across all muscles was significantly greater in the OG (p < 0.001). PA did not moderate the relationship between aging and muscle degeneration. Non-dominant handgrip strength was associated with NMV (p = 0.003). CONCLUSIONS: Age-related atrophy is muscle specific in the lumbar spine; changes in lumbar musculature is independent of PA, handgrip strength may reflect morphological changes in the postural muscles with age. This study supports establishing effective targeted exercise interventions in the lumbar musculature.