Post-transplant immunosuppression increases malignancy risk. Gastric cancer is one of the most common post-transplant malignancies among high-risk groups including Asian patients. Helicobacter pylori is a known risk factor for gastric cancer; however, pre-transplant screening is not standard. This retrospective study assesses the frequency with which patients with end-stage liver disease, prior to liver transplant, are screened for H. pylori using endoscopic or non-endoscopic methods. We conducted a retrospective chart review of 127 patients who underwent upper endoscopy prior to liver transplant. Data were collected for age, ethnicity, indications for endoscopy, endoscopic findings, endoscopic treatment, gastric biopsy results, and antibiotic/proton pump inhibitor use. Non-endoscopic H. pylori testing within 5 years before transplant was recorded. Among 127 patients, 15 were of Asian and 9 were of Indigenous heritage. The most common indication for endoscopy was variceal surveillance (83 patients), then gastrointestinal bleeding (33 patients). Thirty-nine patients had biopsies taken for H. pylori, with four testing positive. Twenty patients had non-endoscopic testing, with three testing positive. Seventy-six patients (60%) underwent no form of testing. In Asian patients, 8 of 15 (53%) had no form of testing. Indigenous and Asian patients demonstrated high positivity rates, with 50% and 14% testing positive, respectively. H. pylori testing was performed in under 40% patients awaiting liver transplant. When tested, positivity was 10% by biopsies and 15% by other methods. Given high prevalence of H. pylori positivity, routine screening via endoscopic or non-endoscopic methods should be employed to mitigate post-transplant gastric malignancy risk. Liver transplant offers a life-saving treatment for many patients with advanced liver disease. However, patients who have received a liver transplant require long-term immunosuppressive medications. Such medications come with side effects that may increase a patient's susceptibility to infections and various cancers. Stomach cancer is one of the more common cancers after transplant, with higher incidences observed in certain ethnic groups, including Asian populations. Helicobacter pylori (H. pylori) is a well-established risk factor for stomach cancer. Currently, routine screening for this bacterium is not standard practice before liver transplant. Our study looked at patients who underwent liver transplantation over a 2-year period. We examined the frequency of testing, methods of testing, and infection rates of H. pylori in liver transplant recipients to better understand current screening practice. We identified that H. pylori infection rate was higher in Asian and Indigenous patients; however, screening remained underutilized despite these patients’ increased risks. Our findings highlight a potential gap in pre-transplant care and suggest that hospitals should consider including routine H. pylori screening as part of standard pre-transplant workup. Detection and early treatment of this infection may decrease the risk of stomach cancers and improve the long-term outcomes of people receiving liver transplants.
As global warming intensifies, heatstroke and complicated liver injury are increasingly becoming the most serious clinical manifestations of heat-related illnesses. However, effective intervention strategies are lacking. This study aims to investigate the protective effect of resveratrol against heatstroke and complicated liver injury and elucidates its molecular mechanism. In this study, a mouse heatstroke model and an AML12 hepatocyte heat exposure model were established. Resveratrol, HSF1 agonist (HSF1A), HSF1 inhibitor (KRIBB11), and HSF1 knockdown were administered in vivo and/or in vitro to investigate the role of HSF1 and validate the core mechanism by which resveratrol protects against liver injury induced by heat exposure. The results showed that resveratrol pretreatment significantly attenuated temperature dysregulation, liver morphology and function induced by heat exposure. Heat exposure upregulated HSF1 expression in both the mouse liver and hepatocytes. HSF1 activation (agonist HSF1A) caused liver injury, lipid deposition and necroptosis typically induced by heat exposure, while HSF1 inhibition and HSF1 knockout reduced these effects. Resveratrol showed the potential to bind to HSF1 and inhibit HSF1 expression in the liver. Moreover, it protected against heat-induced lipid metabolic disorders and necroptosis both in vivo and in vitro, in which necroptosis inhibition did not alter lipid metabolism in hepatocytes. Finally, HSF1 inhibitor (KRIBB11) administration protected against heat stroke and liver injury induced by heat exposure, similar to resveratrol. In conclusion, resveratrol protects against heatstroke and complicated liver injury by HSF1-mediated necroptosis, which might be triggered by lipid metabolic disorders. This study provides an intervention strategy for heatstroke and associated complicated liver injury.
Sarcopenia is associated with increased mortality in patients with cirrhosis, but this association remains unclear when adjusted for portal hypertension. We investigated the association of muscle mass and portal hypertension on liver-related events. This retrospective study (2012-2022) included adult patients with cirrhosis and available hepatic venous pressure gradient (HVPG). Total cross-sectional skeletal muscle index (SMI) and subcutaneous adipose tissue index (SATI) at the third lumbar vertebrae (L3) were measured at the time of HVPG using CT imaging. Sarcopenia is defined as L3-SMI <39 cm2/m2 in female and <50 cm2/m2 in male patients. Logistic regression analyses assessed sarcopenia predictors; Cox regression analyses assessed liver-related events and mortality predictors. A total of 121 patients were included (sarcopenia: 46%, female: 62%, mean age: 58.3 years, MASLD: 34%, median HVPG: 10 mmHg, median MELD score: 13, prior decompensation: 55%). Sarcopenia was more likely in patients with prior decompensation (70% versus 43%, p < 0.003), lower alanine aminotransferase (ALT) (21 versus 40 U/L, p < 0.001), and lower SATI (37.4 versus 76.4 cm2/m2, p < 0.001). After age, prior decompensation, and ALT adjustments, SATI remained an independent predictor of sarcopenia (adjusted odds ratio aOR 0.98 [95% CI 0.97-0.99]). Over a median follow-up of 14.5 months, 59% had liver-related events and 29% died. After HVPG and MELD adjustments, which were significant factors, L3-SMI remained a predictor of liver-related events (adjusted hazard ratio [aHR] 0.98 [95% CI 0.95-0.99]) and mortality (aHR 0.96 [95% CI 0.92-0.99]). Our study demonstrates that low muscle mass predicts liver-related events and mortality independently of portal hypertension and liver disease severity. Low muscle mass is frequent in people with cirrhosis. Our study shows that low muscle mass is linked to an increased risk of liver-related events and mortality after adjusting for the presence of portal hypertension, an important cause of liver events. This supports the need to screen and treat low muscle mass in patients with cirrhosis and prevent the occurrence of liver-related complications.
Although there is substantial clinical comorbidity between atrial fibrillation and liver fibrosis, it is still unknown what molecular processes these conditions share. This study aims to identify key co-disease genes for liver fibrosis and atrial fibrillation. This study systematically identified and validated the pivotal role of NAV2 in both liver fibrosis and atrial fibrillation by integrating multiple transcriptomic datasets from the GEO database, employing a comprehensive analytical framework including differential expression analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction networks, multi-algorithm machine learning, SHapley Additive exPlanations (SHAP), Mendelian randomization, immune infiltration profiling, single-cell sequencing, and gene set enrichment analysis Results: A total of 147 comorbid genes were identified, with machine learning pinpointing 21 core genes. Among these, NAV2 was confirmed as the sole key gene via Mendelian randomisation, partially mediating the causal effect of liver fibrosis on atrial fibrillation (mediation proportion: 24.80%). Single-cell analysis revealed that NAV2 was highly expressed in atrial fibroblasts and hepatic epithelial cells. Gene Set Enrichment Analysis (GSEA) indicated NAV2 participation in metabolic, immune, and fibrosis-related pathways. Epidemiological studies have long demonstrated the clinical comorbidity between liver fibrosis and atrial fibrillation, yet the molecular-level 'common drivers' remain unidentified. This study identifies key comorbid genes for liver fibrosis and atrial fibrillation. NAV2 is a key mediating gene in the co-morbid mechanism of liver fibrosis and atrial fibrillation, demonstrating potential as both a biomarker and therapeutic target.
Alcohol-associated liver disease (ALD) is a growing health care concern, with alcohol use disorder (AUD) being a contributor to liver-related morbidity and mortality. This study examines the practices, perspectives, and challenges faced by Canadian health care providers in managing AUD within the context of ALD. A nationally representative survey was conducted among health care providers involved in ALD management. The survey evaluated practices related to AUD screening, prescribing pharmacotherapy, addiction services referral, and perceived barriers. Alcohol use screening was common (75%), but standardized tools were rarely used (<10%), with barriers including time constraints (61%) and resource limitations (60%). Less than 15% of patients received AUD pharmacotherapy, with lack of training identified as a key barrier. Notably, 47% of providers had never prescribed AUD pharmacotherapy due to low comfort levels (78%). Early and mid-career providers were more likely to prescribe AUD pharmacotherapy compared to their senior counterparts (71% versus 61%, p = 0.02). Acamprosate and naltrexone were the most frequently prescribed medications. Behavioural therapy referrals were reported by 57% of respondents, although patient reluctance (70%) and financial barriers (53%) hindered access. Knowledge gaps regarding AUD pharmacotherapies were prevalent. This study reveals significant gaps in AUD management within ALD care, marked by insufficient screening, underuse of pharmacotherapies, and limited referrals to addiction services. Addressing these issues requires urgent attention through enhanced provider education, integration of addiction care, and systemic reforms. Collaborative efforts among all health care providers are essential to improving care delivery and outcomes for individuals with ALD and AUD. North America, including Canada, is witnessing a concerning increase in the prevalence of alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). As a result, ALD has emerged as a significant contributor to liver-related morbidity and mortality. This study aims to investigate the present state of practice in the management of ALD among health care providers across Canada. By exploring the attitudes, practices, and challenges faced by health care providers, the study seeks to identify existing gaps in the delivery of services related to ALD care and generate evidence-informed insights that address clinical practice concerns specific to the Canadian context. A nationally representative survey was conducted among health care providers involved in ALD management to evaluate practices related to AUD screening, prescribing pharmacotherapy, addiction services referral, and perceived barriers. Providers including specialists in addiction and psychiatry, gastroenterology, and hepatology, as well as social work, were included in the survey. Our results suggest alcohol use screening is common (75%) among health care providers. However, standardized tools were rarely used (<10%), with barriers including time constraints (61%) and resource limitations (60%). Notably, 47% of providers had never prescribed AUD pharmacotherapy due to low comfort levels (78%). Early and mid-career providers were more likely to prescribe AUD pharmacotherapy compared to their senior counterparts (71% versus 61%, p = 0.02). Behavioural therapy referrals were reported by 57% of respondents, although patient reluctance (70%) and financial barriers (53%) hindered access. Our study demonstrated significant gaps in AUD management within ALD care, marked by insufficient screening, underuse of pharmacotherapies, and limited referrals to addiction services. Collaborative efforts among all health care providers are essential to improve care delivery and outcomes for individuals with ALD and AUD. Our study shows that in Canada, we need to have increased provider education, integration of addiction care, and systemic reforms.
This study aimed to evaluate the effects of denosumab and alendronate on bone mineral density (BMD) and liver fibrosis markers in patients with both primary osteoporosis (OP) and metabolic dysfunction-associated steatotic liver disease (MASLD). This was a single-center, retrospective observational study. A total of 60 patients diagnosed with both OP and MASLD were identified from Zhejiang Hospital and categorized into two groups based on their actual treatment received: denosumab (n=30) or alendronate (n=30). Baseline data, including demographic information, clinical characteristics, BMD, and liver fibrosis markers, were obtained from medical records. These measures were again obtained from records after approximately one year of treatment to evaluate changes in BMD and liver fibrosis markers. In the denosumab group, marked improvements in BMD were observed at the lumbar spine (L1-4), femoral neck, and total hip (all P < 0.01). Additionally, there were notable reductions in liver fibrosis markers, such as FIB-4 and NFS (P < 0.01 and P < 0.05, respectively). In the alendronate group, only an increase in lumbar spine (L1-4) BMD was noted (P < 0.05), with no statistically significant changes observed in femoral neck or total hip BMD (P > 0.05), nor in liver fibrosis markers. Denosumab use was associated with improvements in BMD and reductions in liver fibrosis in patients with OP and MASLD, suggesting it may be a promising therapeutic option.
Liver transplantation (LT) is a critical intervention for end-stage liver disease, while complications, such as infections, graft rejection, and metabolic disturbances are common post-transplant. The gut microbiota-bile acid (GM-BA) axis plays a pivotal role in regulating liver function and overall health, influencing both the gut microbiota and bile acid metabolism. This review explored the complex interplay between the gut microbiota (GM) and bile acids during liver transplantation. It also discussed how disruptions in this axis can lead to post-transplant complications, such as infection, rejection, and liver injury. Specifically, the role of microbiota-derived bile acids was assessed in shaping immune responses and metabolic pathways that may impact liver graft function. Furthermore, therapeutic strategies aimed at modulating the GM-BA axis were reviewed to improve post-transplant outcomes, including the use of probiotics, prebiotics, and bile acid receptor modulators. Understanding the mechanisms behind GM-BA dysregulation may provide new directions for improving liver transplant survival and reducing complications.
Liver diseases, encompassing hepatocellular carcinoma, hepatic fibrosis, and metabolic dysfunction-associated steatotic liver disease, constitute a severe global health burden, for which early and accurate diagnosis is in urgent need. Conventional methods are constrained by the invasiveness of biopsy or insufficient spatial resolution of non-invasive imaging, failing to detect early micro-lesions and track pathological progression. Fluorescence imaging features high spatiotemporal resolution, real-time monitoring, and favorable compatibility with small-molecule and nanoscale fluorescent probes, yet its advancement is hampered by fragmented studies that separate probe design parameters from disease-specific requirements. This review coherently integrates two interdependent core modules. The first systematically summarizes liver-adapted probe design strategies, including molecular optimization and nanomaterial engineering, such as spectral optimization for deep hepatic tissue penetration, stimuli-responsive mechanisms for pathological microenvironment recognition, and biocompatibility enhancement for in vivo applicability. The second demonstrates probe applications in the three liver diseases, establishing solid connections between probe design features and disease-specific pathological characteristics. Key challenges and future directions are briefly addressed. This work provides a structured reference for researchers to optimize liver-specific fluorescent probes and explore disease-matched imaging applications.
Patient-partnered basic and translational research is the most productive and meaningful approach to developing informed research questions, generating high-quality data, and producing impactful work. While several organizations have published guidelines for patient-partnered research, few experiential reports in basic science are written from both the patient and researcher perspectives and comment on real-time practical challenges and approaches that ensure the establishment and maintenance of a non-tokenistic, organized, and successful research partnership with patient partners. We describe patient partners' and researchers' experiences working together in a basic science and translational research team studying the drivers of primary sclerosing cholangitis, a rare liver disease for which liver transplantation remains the only treatment to disrupt disease progression. We outline approaches used to support meaningful communication, collaboration, and shared output among project stakeholders, drawing on the perspectives of both basic science researchers and patient representatives involved in long-standing joint research projects. Several practical elements support the success of patient partnership in basic and translational science, including structured communication, clear role definition, mutual respect, sustained engagement, and intentional mechanisms to support patient partners' meaningful contributions. We highlight challenges and strategies used to address them in real time, offering insight into how patient-researcher partnerships can be maintained in an organized, authentic, and non-tokenistic way. This review highlights a patient-partnered research team's experiential insights to bridge the gap between published guidance and real-world practice, reinforcing how authentic patient-researcher partnerships can drive more inclusive and impactful basic and translational science. Involving patients as active partners in research leads to better questions, stronger data, and more meaningful results. While many organizations have created guidelines for including patients in research, there are still very few reports and reviews that describe what this looks like in real time, especially in basic science and translational research in rare liver disease. In this article, we share the experience of both patient partners and researchers working together on a project focused on primary sclerosing cholangitis, a rare liver disease for which liver transplant is the only treatment that can stop progression. We describe how we built and maintained a true partnership by using practical strategies for communication, collaboration, and shared decision making. This work offers lessons learned by both researchers and patient partners and shows how strong patient–researcher relationships can lead to better science and greater impact.
Liver cancer remains a major cause of cancer mortality, and precise CT-based liver tumor segmentation is critical for early diagnosis and personalized treatment. In practice, fully 3D‑supervised training is limited by prohibitive annotation costs and memory and compute demands. Achieving 3D segmentation from purely 2D supervision is attractive yet challenging due to through-plane context loss, inter‑slice inconsistency, weak boundaries, and low contrast and noise. We propose LiT‑WSAG, a 2D‑trained framework that reconstructs voxel‑wise 3D masks. Built upon SAM‑Med2D, it incorporates a wavelet‑guided dual‑scale channel adapter (WDSC‑Adapter) to decouple low- and high-frequency content and enhance multi-scale representations, a lightweight L2.5D neighborhood fusion to recover through‑plane context at near‑2D cost, and adversarial training with a ramped GAN weight ('mean-loss' scheduling) to enforce shape and boundary consistency. Extensive experiments demonstrate significant gains over the baseline across multiple datasets. On the LiTS dataset, LiT‑WSAG achieves slice‑wise and volumetric DSC of 89.74% and 69.27% (+ 8.85 and + 33.64 percentage points over SAM-Med2D); on the WAW‑TACE dataset, the corresponding scores are 96.08% and 82.03%. Furthermore, on the Synapse multi-organ dataset, it attains a state-of-the-art average DSC of 88.23%. These results indicate that LiT‑WSAG delivers robust 3D liver tumor segmentation from 2D supervision, balancing boundary accuracy, noise robustness, and computational efficiency.
The hepatic lobule, the basic unit of the liver, spatially organizes diverse cell types to coordinate metabolism, detoxification, and immune regulation. Yet efficiently reconstructing its hierarchical and vascular microarchitecture in vitro remains a central challenge. Here, we report a vascularized liver-on-a-microsphere (VLOM) system that recreates lobule-like structure and function within individual microscale hydrogel particles. Using a microfluidic-aerosol fabrication strategy, compartmentalized microspheres with rough-textured surface and built-in spatial addressing markers were produced to spatially localize multiple liver cell types and support endothelial barrier formation. The VLOMs exhibit uniform morphology, structural stability, and high viability, accompanied by enhanced hepatic performance, including elevated albumin and urea synthesis and upregulated CYP2B6 and CYP3A4 expression. Metabolomic profiling reveals activation of the alanine-glucose metabolic cycle, which strengthens biosynthetic and detoxification capacities. Supplementation with alanine or glucose further restores hepatic function and mitigates rifampicin-induced hepatotoxicity, underscoring the protective role of this cycle in maintaining metabolic resilience. This scalable, vascularized microsphere system unites microengineering precision and physiological fidelity, offering a high-throughput route to model liver metabolism and evaluate drug responses.
To assess the association between comorbid Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and the risk of developing severe liver disease and cardiovascular disease (CVD) in patients with Chronic Hepatitis B (CHB). CHB Patients were continuously recruited from 2012 to 2022 using the electronic medical record system, and divided into CHB-no MASLD and CHB-MASLD groups. Follow-up continued until January 2024, aiming to compare differences of cumulative incidence between the two groups and to analyze associated risk factors. 8,052 patients were included with a median follow-up of 3.9 years. Compared with CHB-no MASLD group, MASLD was independently associated with a 39% lower risk of severe liver disease (adjusted hazard ratio [aHR]=0.61, 95% confidence interval [CI] 0.49-0.76, p < 0.001), with similar effects in cirrhosis (aHR=0.61, 95% CI 0.45-0.82, p=0.001) and hepatocellular carcinoma (HCC) (aHR=0.57, 95% CI 0.41-0.80, p = 0.001). Stratified analyses indicated the protection effect was more significant in the HBsAg-positive group. Conversely, MASLD was associated with higher CVD risk (aHR=1.16, 95% CI 0.96-1.41, p=0.130), driven by coronary artery disease (aHR=1.91, 95% CI 1.34-2.74, p < 0.001) and arrhythmia (aHR=1.44, 95% CI 1.00-2.08, p=0.053). These findings remained consistent after propensity score matching (PSM). MASLD may reduce the risk of severe liver disease through certain mechanisms, yet it also constitutes a risk factor for CVD, particularly among HBsAg-positive patients.
Non - alcoholic fatty liver disease (NAFLD) is currently the most common steatosis of the liver among Chinese. Nevertheless, a large proportion of individuals go undiagnosed and receive no treatment because of the absence of dependable and efficient diagnostic methods. Given the vital part that fatty acid metabolism (FAM) dysregulation plays in the development of NAFLD, this research aimed to assess the possible worth of FAM regulators as diagnostic biomarkers for NAFLD. GSE89632 (24 normal liver tissue samples and 39 NAFLD liver tissue samples) was utilized as the training cohort. FAM regulators were extracted from the Molecular Signatures Database. The four most crucial FAM regulators, demonstrating the highest significance (FABP4, CPOX, TLR2, and OXT), as identified by the RF model, were used to develop the diagnostic nomogram. To validate the nomogram, analyses of the calibration curve, decision curve (DCA), and clinical impact curve were carried out. FAM subtypes were categorized according to crucial FAM regulators, and genes with differential expression (DEGs) associated with FAM were pinpointed between the subtypes. Further division of gene subtypes was based on FAM-related DEGs. Results: The RF model achieved a higher area under the curve (AUC) than the SVM model in diagnostic ROC analysis. FAM subtype B exhibited higher macrophage infiltration, and gene subtype B consistently exhibited higher infiltration levels of immune cells. FAM scores were also remarkably elevated in FAM subtype B and gene subtype B compared with corresponding FAM subtype A and gene subtype A. The aforementioned genes were then validated by external datasets (GSE48452, GSE66676, and GSE135251). Finally, the expression of key genes was verified in the HepG2 cells and mice. In summary, these findings support the feasibility of using FAM regulators to predict NAFLD occurrence.
This study reports on the use of human liver tissue equivalents (hLTEs) fabricated using major cell types at ratios that recapitulate native liver structure, physiology, and function, to investigate transduction efficiency, cellular tropism, functional impact, and genotoxicity of 2 adeno-associated virus (AAV) serotypes, AAV5 and AAV3b, encoding eGFP under the strong cytomegalovirus (CMV) promoter to ensure ubiquitous transgene expression in all cells. Additionally, AAV5 encoding eGFP or a bioengineered FVIII transgene (lcoET3) under the phosphoglycerate kinase (PGK) promotor was used to identify unique pathways specific to lcoET3 and/or the effects of different promoters. Overall, AAV5 yielded higher eGFP expression, both AAVs transduced endothelial and stellate cells more efficiently than hepatocytes and Kupffer cells, and both altered liver function biomarkers. Differential gene expression analysis showed that multiple genes involved in hepatotoxicity/inflammation were significantly dysregulated, with each serotype, promoter, and transgene producing a distinct pattern of transcriptional alterations. Integration site analysis identified AAV integrations throughout the human genome, with some in the vicinity of multiple genomic loci associated with oncogenesis. Interestingly, numerous integrations were also found within the human mitochondrial genome. Therefore, hLTEs are a valuable platform for human-relevant safety assessment and to gain critical insights for developing safer and more effective liver-directed AAV gene therapy.
This study aimed to investigate whether the natural flavonoid apigenin attenuates hepatocyte senescence and ameliorates high-fat diet (HFD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD) by inhibiting the transforming growth factor-β (TGF-β)/Smad signaling pathway. Both in vivo and in vitro experiments were conducted. In vivo, an HFD-induced MASLD model was established in C57BL/6J mice, which were then treated with apigenin. Hepatic steatosis, inflammation, and fibrosis were assessed by histopathological staining, and the expression of hepatocyte senescence markers (p16, p21, and γH2AX) and key proteins of the TGF-β/Smad pathway were detected by western blotting, immunohistochemistry, and immunofluorescence. Serum lipid metabolism and indicators of liver injury were evaluated using biochemical methods. In vitro, senescence was induced in AML12 mouse hepatocytes with palmitic acid (PA), and the cells were treated with apigenin; anti-senescence effects and TGF-β pathway inhibition were confirmed by senescence-associated β-galactosidase (SA-β-gal) staining and western blotting. In the HFD-induced mouse model, apigenin alleviated hepatic steatosis, inflammation, and fibrosis, and reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). It also decreased senescence markers (p16, p21, and γH2AX) in liver tissues and inhibited TGF-β expression and Smad2/3 phosphorylation. In the PA-treated AML12 cells, apigenin lowered senescence-associated proteins and SA-β-gal-positive cells while suppressing TGF-β/Smad pathway activation. Overexpression of TGF-β partially reversed the anti-senescence effect of apigenin, whereas pharmacological inhibition of TGF-β receptor I with SB431542 further reduced senescence markers and lipid accumulation. These findings indicate that apigenin may mitigate HFD/PA-induced hepatocyte senescence and MASLD-related pathological changes by inhibiting the TGF-β/Smad signaling pathway, offering new insights into its hepatoprotective effects.
Obesity drives chronic diseases such as cardiovascular disease and diabetes. Danlou tablet (DLT), a traditional Chinese medicine formula, is used to treat coronary heart disease by regulating lipid metabolism, suggesting potential for addressing obesity-related metabolic dysfunction. However, its role in obesity and insulin resistance remains unexplored. We investigated the efficacy and mechanisms of DLT against high-fat diet (HFD)-induced obesity and insulin resistance. C57BL/6N mice were fed an HFD for 22 weeks and treated with DLT. A comprehensive phenotypic assessment was conducted, including body weight, glucose tolerance, insulin sensitivity, serum biochemistry, and histopathology of key tissues. To elucidate the therapeutic mechanism, we integrated 16S rRNA gene sequencing of gut microbiota, serum metabolomics (UPLC-Q-TOF-MS), and hepatic transcriptomics. DLT treatment counteracted HFD-induced metabolic dysfunction, reducing body weight, adiposity, dyslipidemia, and insulin resistance, while ameliorating hepatic steatosis, inflammation, and oxidative stress. At the microbial level, DLT restored gut microbial diversity, corrected the Firmicutes/Bacteroidota ratio, and modulated key genera. Metabolomics linked these changes to restored fatty acid β-oxidation. In the liver, transcriptomics showed that DLT reversed HFD-induced gene expression, suppressed inflammatory pathways and enhanced fatty acid oxidation and xenobiotic metabolism. Integrated multi-omics analysis revealed a strong correlative relationship that DLT's therapeutic benefits are associated with the modulation of the gut-liver axis, where remodeling of the gut microbiome is closely linked to the reprogramming of hepatic metabolic pathways. DLT counteracts HFD-induced obesity and insulin resistance via a multi-level regulatory mechanism that is closely associated with the modulation of the gut-liver axis, which involves suppressing pathogenic gut microbes, restoring fatty acid metabolism, and enhancing hepatic lipid catabolism and antioxidant defense. This comprehensive preclinical evidence supports the clinical translation of DLT as a novel therapeutic option for obesity and type 2 diabetes mellitus.
Hepatitis B surface antigen (HBsAg) clearance is regarded as the optimal therapeutic endpoint in patients with chronic hepatitis B (CHB). Pegylated interferon-α (PegIFNα) is currently one of the most effective strategies for achieving this goal. However, the impact of concurrent nonalcoholic fatty liver disease (NAFLD) on the PegIFNα treatment response in CHB patients remains controversial. The aim of this study was to investigate the impact of NAFLD on the antiviral efficacy of PegIFNα in patients with CHB and identify baseline predictors of HBsAg clearance. In this retrospective cohort study, 201 CHB patients receiving PegIFNα monotherapy or PegIFNα in combination with nucleos(t)ide analogs were enrolled and stratified into CHB-only (n = 125) and CHB + NAFLD (n = 76) groups based on the presence of hepatic steatosis. Baseline clinical, virological (including HBsAg levels), and histological characteristics were collected and compared. Cumulative HBsAg clearance, biochemical response, and virological response rates were assessed. Two Cox proportional hazards regression models were constructed to identify independent predictors of HBsAg clearance through univariable and multivariable analyses. No significant difference was observed in the 48-week cumulative HBsAg clearance rate between the CHB + NAFLD and CHB-only groups (18.42% vs 23.2%, P = 0.41), nor in the virological response rates. However, the biochemical response rate was significantly lower in the CHB + NAFLD group (13.79% vs 22.03%, P = 0.042). Multivariate Cox regression analysis identified baseline HBsAg levels (Model 2: HR = 0.36, 95% CI: 0.26-0.51, P < 0.001) and baseline hepatitis B virus (HBV) DNA levels (Model 2: HR = 0.79, 95% CI: 0.63-1.00, P = 0.049) as independent predictors of HBsAg clearance, while NAFLD comorbidity was not independently associated with HBsAg clearance (P = 0.58). In CHB patients receiving PegIFNα-based therapy, concurrent NAFLD did not significantly impair HBsAg clearance rates (18.42% vs 23.2% in week 48). However, it was associated with a reduced biochemical response rate. Baseline levels of HBsAg and HBV DNA served as independent predictors of HBsAg clearance.IMPORTANCEChronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD) are two of the most common liver diseases worldwide, and their coexistence is increasingly frequent due to the rising prevalence of metabolic disorders. Achieving hepatitis B surface antigen clearance is a key therapeutic goal, and pegylated interferon-α (PegIFNα) remains one of the most effective treatments to achieve it. However, it remains unclear whether the presence of NAFLD influences the response to PegIFNα therapy. The study found that NAFLD does not impair the clearance or suppression of hepatitis B virus, but it is associated with delayed normalization of biochemical markers. Whether the hepatitis B surface antigen becomes negative depends mainly on baseline viral levels, rather than the presence of NAFLD. These findings provide important clinical insights for the management of patients with both CHB and NAFLD.
Tobacco exposure is a well-established risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD); however, its global burden remains poorly quantified. This study estimated the global, regional, and national burden of MASLD attributable to tobacco from 1990 to 2023 and projected trends to 2038. Using Global Burden of Disease Study 2023 data, deaths, disability-adjusted life-years (DALYs), age-standardized mortality rates (ASMRs), and age-standardized DALY rates (ASDRs) were estimated across 204 countries and territories. We assessed temporal trends using average annual percentage change, performed decomposition analysis, evaluated cross-national health inequalities with slope and concentration indices, and projected rates to 2038 using Bayesian age-period-cohort models. Globally, deaths increased 2.3-fold (from 1,479 to 3,473) and DALYs 2.2-fold (from 41,636 to 90,682) from 1990 to 2023, whereas the ASMR (0.04 per 100,000) and ASDR (1.00 per 100,000) remained stable. The burden was 6- to 7-fold higher in males than in females, with substantial geographic heterogeneity: declines were observed in the high-income Asia Pacific region, whereas sharp increases occurred in Australasia, Southern Latin America, and North Africa and the Middle East. Population growth and ageing drove the absolute burden increase. Health inequalities widened. Projections indicate declining ASMRs and ASDRs through 2038, with more rapid declines in females. Although age-standardized rates remained stable, the absolute burden more than doubled over three decades, with significant disparities by sex, region, and socioeconomic status. Targeted tobacco control and MASLD prevention strategies are urgently needed, particularly in high-burden regions and among males. Abbreviations: MASLD, metabolic dysfunction-associated steatotic liver disease; DALYs, disability-adjusted life-years; ASDR, age-standardized DALYs rate; ASMR, age-standardized mortality rate; SDI, socio-demographic index. The online version contains supplementary material available at 10.1007/s40200-026-01997-2.
Liver metastases from colon cancer usually appear as well-defined, hypoechoic lesions on imaging, often raising suspicion in older patients with gastrointestinal symptoms. However, atypical presentations can make diagnosis difficult, especially in young patients without obvious signs of cancer. This case highlights the diagnostic challenge caused by cauliflower-like liver lesions in a young woman.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an established adjunct treatment of hemorrhagic shock caused by subdiaphragmatic bleeding. However, evidence for its use in prehospital settings and long-distance transportation in remote locations remains limited. Herein, we report a case of hemorrhagic shock secondary to traumatic liver injury, for which prehospital REBOA was successfully employed. A 41-year-old man sustained multiple traumatic injuries after being run over by heavy machinery. The patient was diagnosed with hemorrhagic shock resulting from a grade IIIb liver injury. Owing to limited local resources and the anticipated clinical deterioration during long-distance transportation to an emergency medical center, a physician-staffed ground ambulance was dispatched. During which the hemodynamic status of the patient deteriorated, tracheal intubation and REBOA were performed in the ambulance. Partial aortic occlusion was initially applied, followed by complete occlusion when cardiac arrest was imminent. On arrival in the operating room, the patient underwent massive blood transfusion, damage-control laparotomy with perihepatic packing, and subsequent transcatheter arterial embolization. No REBOA-related complications occurred. The patient was discharged from the intensive care unit on hospital day seven. Prehospital REBOA may serve as an effective bridge for definitive hemorrhage control during long-distance transportation in resource-limited regions. Successful implementation requires experienced trauma teams and coordinated system-level management.