Self-management in patients with metabolic dysfunction-associated steatotic liver disease: influencing factors and impact on readmission.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease. OBJECTIVE: This study aimed to investigate the self-management ability of patients with MASLD, analyse related factors that may affect self-management ability and evaluate the impact of this ability on readmission. METHODS: The study recruited patients with MASLD admitted to the Department of Infectious Diseases, First Affiliated Hospital of Wenzhou Medical University, between February and October 2021 using the random sampling method. The MASLD diagnosis was based on the guidelines for the prevention and treatment of MASLD. An analysis of patients' self-management ability was conducted using the self-management ability scale for patients with MASLD. Multiple linear regression analysis was used to analyse the factors influencing this self-management ability, and the readmission rate within 1 year was tracked. The patients were rediagnosed as having MASLD upon readmission to the hospital. RESULTS: A total of 241 baseline data items and self-management scale scores for patients with MASLD were collected and investigated. In our study, the normal score range for the self-management scale was 31-155 points, and the self-management scale scores for patients with MASLD was 91.24 ± 16.98, with a low level of self-management accounting for 52.7% and a medium level accounting for 44.8%. The results of the multiple linear regression analysis revealed that marital status, smoking history, fatty liver severity and education were the main factors affecting self-management ability (P < 0.05). The readmission rates were 18.25%, 7.48% and 0%, respectively, after 1 year of follow-up; the difference in survival distribution was statistically significant (P < 0.05). CONCLUSION: The self-management ability of patients with MASLD is relatively low and is primarily influenced by factors such as marital status, smoking history, the severity of fatty liver disease and level of education, which also affect the readmission rate of patients within 1 year.

Impact of Physical Activity on Overall Survival and Liver Cirrhosis Incidence in Steatotic Liver Disease: Insights from a Large Cohort Study Using Inverse Probability of Treatment Weighting.

Physical activity is a cornerstone of a healthy lifestyle, with benefits in managing chronic diseases. This study investigates the relationship between physical activity and liver-related outcomes with or without steatotic liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD and increased alcohol intake (MetALD). The primary outcomes of interest were overall survival in the entire population, individuals without steatotic liver disease, patients with MASLD, and those with MetALD. The secondary outcomes included the incidence of liver cirrhosis. Participants were categorized based on physical activity frequency and Kaplan-Meier survival curves and Cox proportional hazards models were used for analysis. Higher physical activity was associated with significantly better survival in the overall cohort and MASLD cohort before and after inverse probability of treatment weighting (IPTW). In participants without steatotic liver disease and the MetALD cohort, higher physical activity showed significant survival improvement after IPTW. For the incidence of liver cirrhosis, higher physical activity showed significant associations before IPTW in the overall cohort and MASLD cohort, but these associations were not significant after IPTW. Marginal significance was observed in the MetALD cohort before and after IPTW. In conclusion. promoting physical activity may be key in improving liver-related outcomes.

A Healthful Plant-Based Diet as an Alternative Dietary Approach in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Plant-based diets (PBDs) are gaining attention as a sustainable and health-conscious alternative for managing various chronic conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). In the absence of pharmacological treatments, exploring the potential of lifestyle modifications to improve biochemical and pathological outcomes becomes crucial. The adoption of PBDs has demonstrated beneficial effects such as weight control, increased metabolic health and improved coexisting diseases. Nonetheless, challenges persist, including adherence difficulties, ensuring nutritional adequacy, and addressing potential deficiencies. The aim of this review is to provide a comprehensive overview of the impact of PBDs on MASLD, emphasizing the need for tailored dietary interventions with professional support to optimize their effectiveness in preventing and treating metabolic diseases.

Gut microbial metabolites in MASLD: Implications of mitochondrial dysfunction in the pathogenesis and treatment.

With an increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health problem. MASLD is well-known as a multifactorial disease. Mitochondrial dysfunction and alterations in the gut bacteria are 2 vital events in MASLD. Recent studies have highlighted the cross-talk between microbiota and mitochondria, and mitochondria are recognized as pivotal targets of the gut microbiota to modulate the host's physiological state. Mitochondrial dysfunction plays a vital role in MASLD and is associated with multiple pathological changes, including hepatocyte steatosis, oxidative stress, inflammation, and fibrosis. Metabolites are crucial mediators of the gut microbiota that influence extraintestinal organs. Additionally, regulation of the composition of gut bacteria may serve as a promising therapeutic strategy for MASLD. This study reviewed the potential roles of several common metabolites in MASLD, emphasizing their impact on mitochondrial function. Finally, we discuss the current treatments for MASLD, including probiotics, prebiotics, antibiotics, and fecal microbiota transplantation. These methods concentrate on restoring the gut microbiota to promote host health.

Estimating the economic impact of comorbidities in patients with MASH and defining high-cost burden in patients with noncirrhotic MASH.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is associated with high health care costs. This US study investigated the economic burden of MASH, particularly in patients without cirrhosis, and the impact of comorbidities on health care costs. METHODS: This retrospective, observational study used data from patients diagnosed with MASH aged ≥18 years from October 2015 to March 2022 (IQVIA Ambulatory electronic medical record-US). Patients were stratified by the absence or presence of cirrhosis. Primary outcomes included baseline characteristics and annualized total health care cost after MASH diagnosis during follow-up. In addition, this study defined high costs for the MASH population and identified patient characteristics associated with increased health care costs among those without cirrhosis. RESULTS: Overall, 16,919 patients (14,885 without cirrhosis and 2034 with cirrhosis) were included in the analysis. The prevalence of comorbidities was high in both groups; annual total health care costs were higher in patients with cirrhosis. Patients with a high-cost burden (threshold defined using the United States national estimated annual health care expenditure of $13,555) had a higher prevalence of comorbidities and were prescribed more cardiovascular medications. MASH diagnosis was associated with an increase in cost, largely driven by inpatient costs. In patients without cirrhosis, an increase in cost following MASH diagnosis was associated with the presence and burden of comorbidities and cardiovascular medication utilization. CONCLUSIONS: Comorbidities, such as cardiovascular disease and type 2 diabetes, are associated with a higher cost burden and may be aggravated by MASH. Prioritization and active management may benefit patients without cirrhosis with these comorbidities. Clinical care should focus on preventing progression to cirrhosis and managing high-burden comorbidities.

Digital therapeutics lead to clinically significant body weight loss in patients with metabolic dysfunction-associated steatotic liver disease: A systematic review and meta-analysis.

BACKGROUND: Most patients with metabolic dysfunction-associated steatotic liver disease are unable to achieve clinically significant body weight loss with traditional in-person approaches. Digital therapeutic (DTx)-delivered interventions offer promise to remove barriers to weight loss success inherent to traditional resource-heavy in-person programs and at a population level, but their efficacy remains relatively unknown. METHODS: Published studies were identified through May 2023 by searching the following electronic databases: PubMed and Embase (Ovid). DTx intervention was compared to standard of care. The primary outcome was a change in body weight. Secondary outcomes included clinically significant body weight loss (≥5%) and change in liver enzymes. RESULTS: Eight studies comprising 1001 patients met inclusion criteria (mean age: 47 y; body mass index: 33.2 kg/m2). The overall rate of clinically significant body weight loss was 33%, with DTx lifestyle interventions ranging from 4 to 24 months in length. DTx lifestyle intervention achieved statistically significant body weight loss (absolute change -3.4 kg, 95% CI: -4.8 to -2.0 kg, p < 0.01, relative change -3.9%, 95% CI: -6.6 to -1.3, p < 0.01) as well as clinically significant body weight loss of ≥5% (risk ratio: 3.0, 95% CI: 1.7-5.5, p < 0.01) compared to standard of care. This was seen alongside improvement in liver enzymes. CONCLUSIONS: DTx-delivered lifestyle intervention programs lead to greater amounts of body weight loss than traditional in-person lifestyle counseling. These results further support the role of DTx in delivering lifestyle intervention programs to patients with metabolic dysfunction-associated steatotic liver disease and suggest that this scalable intervention offers promise to benefit the billions of patients worldwide with this condition.

The Effect of Mobile Lifestyle Intervention Combined with High-Protein Meal Replacement on Liver Function in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Pilot Randomized Controlled Trial.

While many studies have explored dietary substitutes and mobile apps separately, a combined approach to metabolic dysfunction-associated steatotic liver disease (MASLD) has not been investigated. This study evaluated short-term mobile interventions coupled with partial meal replacement in patients with MASLD. Sixty adults with MASLD and a body mass index ≥25 kg/m2 from a health examination center were randomized into an intervention group using a mobile app with partial meal replacements or a control group receiving standard educational materials. Liver enzyme levels, lipid profiles, and anthropometric measurements were assessed at baseline and after 4 weeks. Twenty-five participants in the intervention group and 24 in the control group completed the trial. Significant reductions were observed in the intervention group for alanine aminotransferase (-28.32 versus [vs.] -10.67, p = 0.006) and gamma-glutamyl transferase (-27.76 vs. 2.79, p = 0.014). No significant changes in aspartate aminotransferase, body weight, or waist circumference were noted in the intervention group. Four weeks of mobile lifestyle intervention incorporating partial meal replacements improved liver enzyme profiles in patients with MASLD. This strategy demonstrated the potential for mitigating elevated liver enzyme levels without altering body weight or waist circumference. Comprehensive and longer-term research is needed to substantiate and elaborate these preliminary outcomes.

Nutritional Interventions, Probiotics, Synbiotics and Fecal Microbiota Transplantation in Steatotic Liver Disease : Pediatric Fatty Liver and Probiotics.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health problem worldwide, and the strongest determinant of liver disease in children. The possible influence of high-fat/low-fiber dietary patterns with microbiota (e.g., increased Firmicutes/Bacteroidetes ratio), and ultimately with MASLD occurrence and progression has been elucidated by several association studies. The possible mechanisms through which microbes exert their detrimental effects on MASLD include gut vascular barrier damage, a shift towards non-tolerogenic immunologic environment, and the detrimental metabolic changes, including a relative reduction of propionate and butyrate in favor of acetate, endogenous ethanol production, and impairment of the unconjugated bile acid-driven FXR-mediated gut-liver axis. The impact of nutritional and probiotic interventions in children with MASLD is described.

What Not to Overlook in the Management of Patients with Type 2 Diabetes Mellitus: The Nephrological and Hepatological Perspectives.

Diabetes mellitus (DM) significantly impacts renal and hepatic function, necessitating comprehensive understanding and management strategies. Renal involvement, namely diabetic kidney disease (DKD), presents a global challenge, with increasing prevalence paralleling DM rates. Lifestyle modifications and pharmacotherapy targeting hypertension and glycemic control have pivotal roles in DKD management. Concurrently, hepatic involvement in DM, characterized by metabolic dysfunction-associated steatotic liver disease (MASLD), presents a bidirectional relationship. DM exacerbates MASLD progression, while MASLD predisposes to DM development and worsens glycemic control. Screening for MASLD in DM patients is of high importance, utilizing non-invasive methods like ultrasound and fibrosis scores. Lifestyle modifications, such as weight loss and a Mediterranean diet, mitigate MASLD progression. Promising pharmacotherapies, like SGLT2 inhibitors and GLP-1 agonists, demonstrate efficacy in both DM and MASLD management. Special populations, such as diabetic individuals undergoing hemodialysis or kidney transplant recipients, demand special care due to unique clinical features. Similarly, DM exacerbates complications in MASLD patients, elevating the risks of hepatic decompensation and hepatocellular carcinoma. Recognizing the interconnectedness of DM, renal, and hepatic diseases underscores the need for multidisciplinary approaches for optimal patient outcomes. The present review aims to present the main characteristics and crucial points not to be overlooked regarding the renal and hepatic involvement in DM patients focusing on the inter-relationships between the renal and the hepatic involvements.

The Role of Extrahepatic Features on the Development and Management of Hepatocellular Carcinoma in Steatotic Liver Disease.

As the most common type of primary liver cancer, hepatocellular carcinoma (HCC) is reportedly the third leading cause of cancer-related death globally. Advanced steatotic liver disease (SLD) emerges as the most prominent contributor to HCC worldwide. In this paper, we review the extrahepatic features of metabolic dysfunction-associated SLD that exacerbate the risk for HCC, including insulin resistance, obesity-related factors such as physical inactivity and dietary patterns, as well as influences of genetics, ethnicity, gender-specific hormonal differences, alcohol-associated liver disease (ALD), smoking habits, and alterations in gut microbiota. Additionally, the mechanisms underlying how these extrahepatic features contribute to the development, as well as the detection and surveillance of HCC, are elaborated. With a better understanding of these factors, targeted interventions can be designed to prevent HCC development or ameliorate its clinical outcomes.

Role and therapeutic perspectives of extracellular vesicles derived from liver and adipose tissue in metabolic dysfunction-associated steatotic liver disease.

The global epidemic of metabolic diseases has led to the emergence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), which pose a significant threat to human health. Despite recent advances in research on the pathogenesis and treatment of MASLD/MASH, there is still a lack of more effective and targeted therapies. Extracellular vesicles (EVs) discovered in a wide range of tissues and body fluids encapsulate different activated biomolecules and mediate intercellular communication. Recent studies have shown that EVs derived from the liver and adipose tissue (AT) play vital roles in MASLD/MASH pathogenesis and therapeutics, depending on their sources and intervention types. Besides, adipose-derived stem cell (ADSC)-derived EVs appear to be more effective in mitigating MASLD/MASH. This review presents an overview of the definition, extraction strategies, and characterisation of EVs, with a particular focus on the biogenesis and release of exosomes. It also reviews the effects and potential molecular mechanisms of liver- and AT-derived EVs on MASLD/MASH, and emphasises the contribution and clinical therapeutic potential of ADSC-derived EVs. Furthermore, the future perspective of EV therapy in a clinical setting is discussed.

Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study.

BACKGROUND: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. METHODS: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). DISCUSSION: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. TRIAL REGISTRATION: ISRCTN ISRCTN14957538. Registered in October 2022.

Hope on the Horizon: Promising Therapies for Steatotic Liver Disease.

Steatotic liver disease (SLD) is a highly prevalent chronic liver disease with significant challenges for global health. The pathophysiology of SLD involves an interplay among genetic, endocrine, and metabolic factors. Successful management of SLD entails accurate diagnosis and disease monitoring through noninvasive methods such as advanced imaging techniques and biomarkers. Many emerging pharmacotherapies for SLD are now in the pipeline, which target different pathways like collagen turnover, fibrogenesis, inflammation, and metabolism. The recent approval of resmetirom for noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) has been a milestone in addressing the unmet medical need for an efficacious SLD treatment. Finally, the potential of personalized medicine approaches and interdisciplinary cooperation in improving patient outcomes and reducing disease burden should be strongly pursued. SIGNIFICANCE STATEMENT: The healthcare burden due to steatotic liver disease (SLD) is enormous. This perspective sheds light on the recent advances in understanding the pathophysiology and diagnosis of SLD as well as promising drug development approaches.

Effect of smartphone-assisted lifestyle intervention in MASLD patients: a randomized controlled trial.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is emerging globally as a significant problem. The mainstay of treatment is lifestyle intervention (LSI). We hypothesized that providing information regarding LSI and MASLD through a social media application generally used in the respective society would improve clinical outcomes in MASLD more than standard of care (SOC). This is a randomized controlled study in noncirrhotic MASLD patients aged 18-65 years in Thailand. Eligible patients were randomly assigned to either the control (SOC) or intervention arm. Patients in both groups received standard LSI advice. Infographics about MASLD and LSI information were sent to the intervention group every 3-7 days via the LINE official account. The outcomes are changes in liver steatosis and liver stiffness by FIBROSCAN at 24 weeks, as well as weight loss, body composition, and serum alanine aminotransferase (ALT) level between the two groups. A total of 122 patients were enrolled. The median age of eligible participants was 53 years, 64.7% were female, and median body mass index was 27.3 kg/m2. After a complete 24-week study period, both groups had an improvement in weight, ALT level, liver steatosis, and fat mass, but the differences in those changes between groups were not statistically significant. Interestingly, a significant improvement in liver stiffness was observed in the intervention group than in the control group (- 0.7 ± 1.8 kPa vs. 0.1 ± 2.4 kPa, P = 0.035). Encouraging LSI and delivering MASLD information via a social media application (LINE official account) to patients with MASLD demonstrated a better outcome of liver stiffness measurement than SOC.Clinical trial number: TCTR20210304002 (04/03/2021) ( http://www.thaiclinicaltrials.org/show/TCTR20210304002 ).

Nanoformulations for the diagnosis and treatment of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive phase of metabolic dysfunction-associated steatotic liver disease (MASLD) that develops into irreversible liver cirrhosis and hepatocellular carcinoma, ultimately necessitating liver transplantation as the sole life-saving option. However, given the drawbacks of liver transplantation, including invasiveness, chronic immunosuppression, and a lack of donor livers, prompt diagnosis and effective treatment are indispensable. Due to the limitations of liver biopsy and conventional imaging modalities in diagnosing MASH, as well as the potential hazards associated with liver-protecting medicines, numerous nanoformulations have been created for MASH theranostics. Particularly, there has been significant study interest in artificial nanoparticles, natural biomaterials, and bionic nanoparticles that exhibit exceptional biocompatibility and bioavailability. In this review, we summarized extracellular vesicles (EVs)-based omics analysis and Fe3O4-based functional magnetic nanoparticles as magnetic resonance imaging (MRI) contrast agents for MASH diagnosis. Additionally, artificial nanoparticles such as organic and inorganic nanoparticles, as well as natural biomaterials such as cells and cell-derived EVs and bionic nanoparticles including cell membrane-coated nanoparticles, have also been reported for MASH treatment owing to their specific targeting and superior therapeutic effect. This review has the potential to stimulate advancements in nanoformulation fabrication techniques. By exploring their compatibility with cell biology, it could lead to the creation of innovative material systems for efficient theragnostic uses for MASH. STATEMENT OF SIGNIFICANCE: People with metabolic dysfunction-associated steatohepatitis (MASH) will progress to fibrosis, cirrhosis, or even liver cancer. It is imperative to establish effective theragnostic techniques to stop MASH from progressing into a lethal condition. In our review, we summarize the advancement of artificial, natural, and bionic nanoparticles applied in MASH theragnosis. Furthermore, the issues that need to be resolved for these cutting-edge techniques are summarized to realize a more significant clinical impact. We forecast the key fields that will advance further as nanotechnology and MASH research progress. Generally, our discovery has significant implications for the advancement of nanoformulation fabrication techniques, and their potential to be compatible with cell biology could lead to the creation of innovative materials systems for effective MASH theragnostic.

Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

Clinical improvement effect of regulating gut microbiota on metabolic dysfunction-associated steatotic liver disease: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is constantly rising globally. There are barely any effective medications or supplements for the management of MASLD. We aim to systematically evaluate the most current evidence for gut microbiota-regulating supplements in patients with MASLD. METHODS: We searched multiple electronic data for randomized controlled trials (RCTs) published from January 1, 2012, to July 15, 2023. The intervention measures included probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The control group was treated with a placebo or usual care. The intervention duration was divided into two periods (>12 weeks and ≤12 weeks). Adequate evaluation data for antibiotics and FMT have not been obtained. Therefore, the other three microbiota regulators are the primary evaluation measures in this study. RESULTS: We found that probiotics alone could not improve clinical indicators in MASLD patients. However, synbiotics exhibited an improvement in reducing liver steatosis, TNF-ɑ levels, and increasing HDL-c levels, and the inflammatory markers of liver cells (ALT and AST) were also improved. For the effective intervention duration, this systematic review suggested that around 12 weeks is an ideal intervention cycle for MASLD patients. CONCLUSIONS: This meta-analysis supported the modulation of gut microbiota with synbiotics in the management of MASLD.

BRIDGE to liver health: implementation of a group telehealth psychoeducational program through shared medical appointments for MASLD management.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significantly costly and increasingly prevalent disease, with treatment focused on lifestyle intervention. Integrating education and behavioral health into clinical care offers opportunities to engage and empower patients to prevent progression of liver disease. We describe the design and implementation of Behavioral Resources and Intervention through Digital Group Education (BRIDGE), a 6-session group telehealth program led by advanced practice providers (APPs) in 90-min shared medical appointments (SMAs) with small groups of MASLD patients in an academic outpatient hepatology clinic. The program contains multi-component group interventions, with didactic education and behavioral coaching, while leveraging peer-based learning and support. METHODS: A mixed-methods exploratory pilot study was conducted. Feasibility and acceptability of the clinical intervention were assessed by tracking recruitment, attendance, and retention of BRIDGE participants, patient interviews, and debriefing of clinician and staff views of the clinical program. Implementation metrics included program development time, workflow and scheduling logistics, and billing compliance for sustainability. Finally, patient parameters including changes in liver enzymes, FIB-4, weight, and BMI from pre- to post-BRIDGE were retrospectively analyzed. RESULTS: We included 57 participants (median age 57, interquartile range (IQR) 50 - 65 years), 38 (67%) female, 38 (67%) white, and 40% had public insurance. Thirty-three (58%) participants completed all six sessions, while 43 (75%) attended at least five sessions. Patients who completed all sessions were older (median age 61 vs 53.5; p = 0.01). Gender, race/ethnicity, and insurance type were not significantly associated with missed sessions, and patients had similar rates of completion regardless of weight, BMI, or stage of liver disease. Barriers to completion included personal illness, family reasons, work commitments, or insurance issues. Prior to BRIDGE, median BMI was 31.9 (SD 29 - 36), with a median weight loss of 2 pounds (IQR -2 - 6) after BRIDGE. CONCLUSION: The BRIDGE telehealth SMA program was feasible, well-attended, and positively reviewed. This pilot study informs future iterations of program development and evaluation of outcome measures.

Human umbilical cord mesenchymal stem cells alleviate fatty liver ischemia-reperfusion injury by activating autophagy through upregulation of IFNγ.

Liver ischemia-reperfusion injury (IRI) is an important factor affecting the prognosis of liver transplantation, and extended criteria donors (e.g., steatosis donor livers) are considered to be more sensitive to ischemia-reperfusion injury in liver transplantation. Currently, the application of human umbilical cord mesenchymal stem cells (hMSCs) has great promise in the treatment of various injuries in the liver. This study aimed to investigate the therapeutic role and mechanism of hMSCs in fatty liver IRI. After more than 8 weeks of high-fat chow feeding, we constructed a fatty liver mouse model and established ischemic injury of about 70% of the liver. Six hours after IRI, liver injury was significantly alleviated in hMSCs-treated mice, and the expression levels of liver enzyme, inflammatory factor TNF-α, and apoptotic proteins were significantly lower than those of the control group, which were also significant in pathological sections. Transcriptomics analysis showed that IFNγ was significantly upregulated in the hMSCs group. Mechanistically, IFNγ, which activates the MAPK pathway, is a potent agonist that promotes the occurrence of autophagy in hepatocytes to exert a protective function, which was confirmed by in vitro experiments. In summary, hMSCs treatment could slow down IRI in fatty liver by activating autophagy through upregulation of IFNγ, and this effect was partly direct.

Metabolic Dysfunction-Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options.

The epidemiological burden of liver steatosis associated with metabolic diseases is continuously growing worldwide and in all age classes. This condition generates possible progression of liver damage (i.e., inflammation, fibrosis, cirrhosis, hepatocellular carcinoma) but also independently increases the risk of cardio-metabolic diseases and cancer. In recent years, the terminological evolution from "nonalcoholic fatty liver disease" (NAFLD) to "metabolic dysfunction-associated fatty liver disease" (MAFLD) and, finally, "metabolic dysfunction-associated steatotic liver disease" (MASLD) has been paralleled by increased knowledge of mechanisms linking local (i.e., hepatic) and systemic pathogenic pathways. As a consequence, the need for an appropriate classification of individual phenotypes has been oriented to the investigation of innovative therapeutic tools. Besides the well-known role for lifestyle change, a number of pharmacological approaches have been explored, ranging from antidiabetic drugs to agonists acting on the gut-liver axis and at a systemic level (mainly farnesoid X receptor (FXR) agonists, PPAR agonists, thyroid hormone receptor agonists), anti-fibrotic and anti-inflammatory agents. The intrinsically complex pathophysiological history of MASLD makes the selection of a single effective treatment a major challenge, so far. In this evolving scenario, the cooperation between different stakeholders (including subjects at risk, health professionals, and pharmaceutical industries) could significantly improve the management of disease and the implementation of primary and secondary prevention measures. The high healthcare burden associated with MASLD makes the search for new, effective, and safe drugs a major pressing need, together with an accurate characterization of individual phenotypes. Recent and promising advances indicate that we may soon enter the era of precise and personalized therapy for MASLD/MASH.