Exercise is the cornerstone of metabolic-associated fatty liver disease(MAFLD) management and a core approach to reversing hepatic steatosis and reducing cardiovascular risk. Currently, there are no effective therapeutic drugs approved by regulatory authorities for MAFLD, thus patients with MAFLD need more precise exercise prescription guidance. However, there are relatively few exercise guidelines specifically for MAFLD patients at present. With the continuous exploration of this field by experts and scholars, in the past two years, American College of Sports Medicine (ACSM) and Exercise and Sport Science Australia (ESSA) respectively released expert consensuses on exercise guidance recommendations for patients with MAFLD: American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable Report on Physical Activity and Nonalcoholic Fatty Liver Disease and Exercise in the Management of Metabolic-associated Fatty Liver Disease (MAFLD) in Adults: a Position Statement from Exercise and Sport Science Australia. These two expert consensuses comprehensively put forward guiding opinions from the perspectives of the mechanism by which exercise improves hepatic steatosis, the impact of different types of exercise on MAFLD, the benefits of exercise for MAFLD patients, and the formulation of exercise prescriptions. This article interpreted the main contents of the expert consensus, aiming to provide more scientific exercise guidance for domestic MAFLD patients.
Metabolic associated fatty liver disease (MAFLD) and hypertension are prevalent chronic conditions in older adults, with accumulating evidence linking both to metabolic dysfunction. The cardiometabolic index (CMI) is a composite parameter that evaluates visceral adipose distribution and metabolic status, yet its association with incident hypertension among elderly MAFLD patients remains to be elucidated.
To investigate the association of CMI with incident hypertension in elderly patients with MAFLD, and to evaluate the predictive value of CMI for hypertension development in this population.
Elderly non-hypertensive patients diagnosed with MAFLD during health check-ups at Yingzhong and Zijin Community Health Centers affiliated with Changzhi People's Hospital between January and December 2021 were enrolled. Follow-up investigations were conducted from January 2022 to December 2024, and 426 elderly MAFLD patients who completed follow-up were ultimately included in this study. Baseline characteristics and relevant clinical data were collected, and CMI was calculated. Participants were stratified into three tertile groups based on CMI: T1 (CMI<0.467, n=141), T2 (0.467≤CMI<0.758, n=142), and T3 (CMI≥0.758, n=143). They were further categorized into non-hypertension (n=355) and hypertension (n=71) groups based on incident hypertension during follow-up. Kaplan-Meier survival analysis was performed to estimate the cumulative incidence of hypertension across CMI groups, with between-group differences assessed using the Log-rank test. Multivariate Cox proportional hazards regression and restricted cubic spline (RCS) analysis were used to evaluate the association between CMI and incident hypertension. Sex-stratified analysis and sensitivity analysis were performed to examine the robustness of this association.Furthermore, time-dependent receiver operating characteristic (ROC) curves were constructed to assess the predictive performance of CMI for hypertension development in elderly MAFLD patients.
During a median follow-up period of 36.00 (27.75, 38.00) months, 71 patients (16.7%) developed incident hypertension. There were statistically significant differences between the non-hypertension and hypertension groups in age, waist circumference, BMI, CMI, TC, TG, LDL-C, and HDL-C (P<0.05). Log-rank test demonstrated that the cumulative incidence of hypertension increased significantly across T1 to T3 groups with elevated CMI levels (χ2=26.468, P<0.001). Multivariate Cox proportional hazards regression analysis revealed that when analyzed as a continuous variable, CMI was significantly and positively associated with incident hypertension in elderly MAFLD patients after adjusting for relevant confounders (HR=1.927, 95%CI=1.381-2.689, P<0.001). When CMI was analyzed as a categorical variable with the T1 group as the reference, the risk of developing hypertension was significantly higher in the T3 group after adjusting for confounders (HR=5.453, 95%CI=2.268-13.109, P<0.001). Interaction analysis showed no statistically significant interaction between CMI and gender (Pinteraction=0.557). Sensitivity analysis demonstrated that the association between CMI and hypertension remained significant after excluding participants with MAFLD remission. RCS analysis showed a non-linear dose-response relationship between CMI and the risk of hypertension in elderly MAFLD patients (Pnon-linearity=0.005). The risk of hypertension exhibited a continuous upward trend with increasing CMI levels, which plateaued when CMI exceeded 1.185. Time-dependent ROC curve analysis showed that CMI demonstrated optimal predictive performance for hypertension at 24 months of follow-up, with an AUC of 0.722 (95%CI=0.618-0.827). Over time, the AUC decreased to 0.648 (95%CI=0.537-0.759) and 0.652 (95%CI=0.542-0.763) at 30 and 36 months, respectively.
CMI is significantly positively associated with incident hypertension in elderly MAFLD patients, and its measurement can be used to assess the short-term (24-month) risk of hypertension development in this population.
Metabolic associated fatty liver disease (MAFLD), as the most prevalent chronic liver disease worldwide, features a complex and multifactorial pathogenesis, and no targeted therapeutics are currently available. This review focuses on the E3 ubiquitin ligase Parkin, providing a systematic analysis of its classical and non-classical functions during MAFLD progression. We particularly highlight Parkin's pivotal roles in multiple pathological processes, including the regulation of apoptosis and pyroptosis, mediation of endoplasmic reticulum-mitochondria crosstalk, reprogramming of lipid metabolism, and modulation of hepatic stellate cell activation. It is well established that Parkin-mediated mitophagy via the PINK1/Parkin pathway serves as a central mechanism for maintaining hepatic metabolic homeostasis and suppressing inflammatory responses. However, growing evidence from cross-disease model studies suggests that under lipotoxic stress, Parkin's functional repertoire extends far beyond mitochondrial quality control. Building on this evidence, we propose that Parkin likely participates may potentially participate in multiple MAFLD pathogenic pathways through a series of non-canonical ubiquitination events. Consequently, future therapeutic strategies in MAFLD should aim at coordinated multi-pathway intervention. This perspective opens new avenues for innovative drug discovery targeting Parkin.
