Metabolism-associated fatty liver disease (MAFLD) is a multifaceted disease that involves complex interactions between various organs, including the gut and heart. It is defined by hepatic lipid accumulation and is related to metabolic dysfunction, obesity, and diabetes. Understanding the intricate interplay of the gut–liver–heart crosstalk is crucial for unraveling the complexities of MAFLD and developing effective treatment and prevention strategies. The gut–liver crosstalk participates in the regulation of the metabolic and inflammatory processes through host–microbiome interactions. Gut microbiota have been associated with the development and progression of MAFLD, and its dysbiosis contributes to insulin resistance, inflammation, and oxidative stress. Metabolites derived from the gut microbiota enter the systemic circulation and influence both the liver and heart, resulting in the gut–liver–heart axis playing an important role in MAFLD. Furthermore, growing evidence suggests that insulin resistance, endothelial dysfunction, and systemic inflammation in MAFLD may contribute to an increased risk of cardiovascular disease (CVD). Additionally, the dysregulation of lipid metabolism in MAFLD may also lead to cardiac dysfunction and heart failure. Overall, the crosstalk between the liver and heart involves a complex interplay of molecular pathways that contribute to the development of CVD in patients with MAFLD. This review emphasizes the current understanding of the gut–liver–heart crosstalk as a foundation for optimizing patient outcomes with MAFLD.

Alcohol-associated liver disease (ALD) includes a spectrum from steatosis and steatohepatitis to cirrhosis and hepatocellular carcinoma driven by oxidative stress, immune activation, and systemic inflammation. Ethanol metabolism through alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P450 2E1 generates reactive oxygen and nitrogen species, leading to mitochondrial dysfunction, hepatocellular injury, and activation of inflammatory and fibrogenic pathways. Beyond hepatic effects, ALD engages the gut–liver–brain axis, where microbial dysbiosis, blood–brain barrier disruption, and neuroinflammation contribute to cognitive impairment and cerebrovascular risk. The emerging concept, metabolic dysfunction-associated steatotic liver disease and increased alcohol intake (MetALD), presents the synergistic impact of alcohol and metabolic comorbidities, enhancing oxidative injury and fibrosis. This review summarizes key mechanisms connecting oxidative stress to multisystem pathology and highlights the need for precision therapies targeting redox imbalance, immune dysregulation, and gut–brain–liver interactions to improve outcomes in ALD and MetALD.

Chronic alcohol consumption induces oxidative stress not only in the liver but also in the gastrointestinal tract, where prolonged intestinal ethanol absorption plays a pivotal and underrecognized role. This review reframes ethanol pharmacokinetics to emphasize sustained jejunal and ileal uptake, which maintains elevated blood alcohol levels and perpetuates redox imbalance across the gut–liver axis. We integrate recent findings on ethanol-induced barrier dysfunction, CYP2E1-mediated ROS production, microbial dysbiosis, and mitochondrial disruption, proposing that the intestine is an active site of injury and a driver of systemic inflammation. Key mechanistic insights reveal that gut-derived endotoxins, compromised epithelial integrity, and microbiome–mitochondria interactions converge to exacerbate hepatic and extrahepatic damage. We further explore emerging therapeutic strategies—ranging from NAD⁺ repletion and probiotics to fecal microbiota transplantation—that target this upstream pathology. Recognizing prolonged intestinal ethanol absorption as a clinically meaningful phase offers new directions for early intervention and redox-based treatment in alcohol-associated disease.

This study examines the impact of glucosamine on the progression and outcomes of metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction and alcohol-associated liver disease (MetALD) using a large scale cohort. Present study utilized inverse probability of treatment weighting (IPTW) to adjust for confounders in this cohort study. Participants were classified based on glucosamine use, and primary and secondary outcomes included all-cause mortality, liver cirrhosis, cardiovascular disease, cerebrovascular disease, and chronic kidney disease (CKD) incidences. Cox proportional hazards models were used to assess hazard ratios and 95 % confidence intervals. We found that glucosamine significantly reduces all-cause mortality in MASLD and MetALD cohorts after IPTW adjustment (P < 0.001). Additionally, glucosamine use was associated with lower liver cirrhosis incidence in MASLD both before (P = 0.003) and after IPTW adjustment (P = 0.046). Glucosamine also decreased cardiovascular disease risk in MASLD (P < 0.001) and MetALD (P = 0.037) cohorts, though it showed no significant impact on cerebrovascular disease incidence. Furthermore, glucosamine use was associated with a significantly lower incidence of CKD in the MASLD cohort (P = 0.034) and the entire cohort (P = 0.030), but not in the No steatotic liver disease cohort or MetALD cohort. The findings suggest that glucosamine could be a beneficial supplementary therapy for managing steatotic liver diseases, particularly for patients at high risk for cardiovascular and renal complications. Further clinical trials are required to validate these potential benefits.

Alcohol-associated liver disease (ALD) has become a major global concern, but the development of effective drugs remains a challenge despite numerous preclinical and clinical pieces of research on the effects of natural compounds. To address this, a meta-analysis was conducted on the efficacy of Panax ginseng for ALD based on preclinical studies. We identified 18 relevant studies from PubMed, Web of Science, and Cochrane Library database and evaluated their methodological quality using the Systematic Review Centre for Laboratory animal Experimentation tool. We analyzed the data using I², p-values, and fixed effects models to assess overall efficacy and heterogeneity. The results of the meta-analysis suggested that Panax ginseng treatment is effective in reducing the levels of inflammatory markers associated with hepatic injury caused by ALD in animal experiments. Additionally, the administration of Panax ginseng was found to down-regulate inflammatory cytokines and attenuate lipid metabolism in ALD. Moreover, Panax ginseng markedly improved the antioxidant systems in ALD. Therefore, we concluded that Panax ginseng has the potential to be a promising therapeutic agent for ALD. Further research is needed to confirm these findings and to determine the optimal dosage and duration of treatment for patients with ALD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern with limited therapeutic options. Multivitamins, widely consumed dietary supplements, have been proposed to modulate oxidative stress and inflammation, potentially impacting MASLD progression. However, their efficacy in reducing mortality and other complications in MASLD remains unclear. Using data from the UK Biobank with 7 years of median follow-up period, this study assessed the association between multivitamin use and health outcomes, including all-cause mortality, liver-related mortality, cardio-cerebrovascular disease (CVD), and chronic kidney disease (CKD), in individuals with MASLD and those without steatotic liver disease. Inverse probability of treatment weighting (IPTW) was employed to adjust for confounders. Multivitamin users showed a significantly lower all-cause mortality risk in the MASLD cohort both before (HR: 0.88, 95% CI 0.81–0.95, P = 0.034) and after (HR: 0.94, 95% CI 0.88–1.00, P = 0.037) IPTW adjustment. Multivitamin use was also associated with the lower risk of CVD (HR: 0.72, 95% CI 0.68–0.76, P < 0.001) and CKD (HR: 0.73, 95% CI 0.67–0.81, P < 0.001) in the MASLD cohort. No significant reduction was found for liver-related mortality or liver cirrhosis incidence. These findings suggest that multivitamins might provide broader protective effects in populations with metabolic dysfunction. Further research is needed to clarify their role in liver-specific outcomes.