Search Results (3,106)

Background: Liver regeneration is essential for restoring hepatic mass after injury or resection, with metabolic reprogramming as a critical driver. Radix Rehmanniae Praeparata (RRP), a traditional Chinese medicine for chronic liver diseases, regulates glucose and lipid metabolism. This study evaluated the effects of RRP on liver regeneration and explored the underlying mechanisms. Methods: A 70% partial hepatectomy (PHx) mouse model was employed, and integrated transcriptomic and metabolomic analyses were conducted to characterize the global features of RRP-induced metabolic reprogramming and its association with hepatocyte proliferation. To further validate these findings, the AML12 hepatocyte cell line and primary mouse hepatocytes were used to identify key targets of RRP. Results: RRP significantly enhanced liver regeneration, as evidenced by the upregulation of hepatocyte proliferation markers. Transcriptomic, metabolomic, and biochemical analyses showed that RRP promoted lipid catabolism and H3K27ac remodeling-dependent hepatocyte proliferation by increasing acetyl-CoA flux. RRP also enhanced carbohydrate consumption and pentose phosphate pathway, as well as protecting mitochondrial integrity, which contribute to both energy production and nucleotide synthesis during cell cycle progression. Notably, RRP-induced AMPK activation was involved in these metabolic reprogramming events, since pharmacological inhibition of AMPK with Compound C attenuated the promotive effects of RRP on liver regeneration. Conclusions: RRP promotes liver regeneration by enhancing metabolic reprogramming mediated by AMPK activation, highlighting its therapeutic potential for metabolic adaptation and postoperative recovery in compromised liver. Full article

Background: Celiac disease (CD) is a chronic immune-mediated enteropathy that is treated exclusively with a lifelong gluten-free diet (GFD). Hepatic involvement, including hepatic steatosis (HS), is common in both newly diagnosed and long-term GFD-treated CD patients. Limited data exist regarding HS prevalence and risk factors in CD, and the effects of dietary patterns, including GFD and the Mediterranean diet (MD), remain unclear. Objective: This study investigated the prevalence and severity of HS in newly diagnosed, pre-GFD and GFD-treated CD patients compared to non-celiac control subjects, while assessing the influence of dietary adherence. Methods: In a nested cross-sectional study within the ARCTIC trial (NCT05530070), 290 Hungarian adults were enrolled (60 pre-GFD CD, 156 CD on GFD, and 74 control subjects). HS was assessed by ultrasonography, and dietary adherence was evaluated using the Standardized Dietitian Evaluation and Mediterranean Diet Score (MDS). Binary regression models were applied to identify predictors of HS. Results: HS was diagnosed in 34% of participants, most frequently in pre-GFD CD patients. BMI was the strongest predictor of HS both overall and within the CD cohort (OR = 1.27; 95% CI: 1.16, 1.42; p < 0.001). Neither adherence to GFD nor overall MD adherence significantly influenced the prevalence of HS. Severity of HS correlated with higher BMI, older age, and diabetes prevalence, while individual MD components, including olive oil consumption, were associated with milder HS. Conclusions: HS is more prevalent in CD patients, particularly pre-GFD patients, and is strongly associated with BMI. While overall dietary patterns did not significantly impact HS, certain diet components may modulate severity. Full article

This narrative review explores the role of artificial light at night (ALAN) as an emerging environmental determinant of liver and metabolic health, with particular emphasis on its contribution to metabolic dysfunction-associated steatotic liver disease (MASLD). The objective was to synthesize and critically evaluate experimental and epidemiological evidence linking nocturnal light exposure, circadian disruption, and hepatic metabolic alterations. Literature was retrieved from PubMed, Scopus, Web of Science, and Google Scholar databases covering the period 1980–2025 using predefined search terms related to ALAN, circadian rhythm disturbance, melatonin suppression, sleep disruption, and MASLD. Relevant experimental studies in animal models and observational studies in humans were included. Evidence indicates that blue-enriched light (~460–480 nm) suppresses melatonin, desynchronizes central and hepatic circadian clocks, and disrupts glucose–lipid metabolism, leading to insulin resistance, oxidative stress, and hepatic steatosis. Chronic ALAN exposure also alters gut microbiota composition and increases intestinal permeability, suggesting a light–gut–liver axis in MASLD pathogenesis. Human epidemiological studies associate higher environmental ALAN exposure with obesity, metabolic syndrome, and poor sleep quality—recognized risk factors for MASLD. Recognizing ALAN as a modifiable environmental exposure highlights the need for public health strategies and clinical guidelines to mitigate its metabolic impact through improved lighting design and sleep hygiene. Full article

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of liver disease in the United States and frequently coexists with other liver diseases. Despite growing interest, the presence of MASLD in patients with primary sclerosing cholangitis (PSC) remains underexplored. This study aimed to assess the prevalence and characteristics of the MASLD-PSC overlap syndrome, with a specific focus on patient-reported outcomes such as pruritus and fatigue. Methods: A cross-sectional analysis was performed within a prospective cohort of patients with PSC enrolled in the Autoimmune Liver Diseases Registry at a United States tertiary medical center (2018–2024). MASLD overlap was established based on evidence of hepatic steatosis on liver imaging or biopsy, combined with at least one cardiometabolic risk factor. Fatigue and pruritus were assessed using the Chronic Liver Disease Questionnaire (CLDQ) and the 5D Itch Scale. Ordinal logistic regression models were used to explore the potential impact of MASLD overlap on fatigue and pruritus severity. Results: Among 103 PSC patients, 33% had MASLD overlap. These patients were older (55 vs. 46 years, p = 0.006), had a higher BMI (30 vs. 25 kg/m², p < 0.001), and were more likely to have small bile duct involvement (43% vs. 12%, p = 0.002). A history of liver transplantation (LT) was noted in 18% of PSC-only patients, compared to 3% of those with PSC/MASLD (p = 0.055). MASLD overlap was significantly associated with higher pruritus intensity (OR 3.09, 95% CI 1.02–9.28, p = 0.044), but was paradoxically linked to lower fatigue levels (OR 0.37, 95% CI 0.16–0.85, p = 0.020). Conclusions: Patients with PSC/MASLD exhibit distinct clinical features. MASLD overlap was found to significantly impact patient-reported outcomes, with lower fatigue intensity but increased pruritus severity, suggesting a role for metabolic or inflammatory pathways, warranting further investigation. Full article

Background: Pyruvate kinase deficiency (PKD) is the most prevalent enzymatic defect of the glycolytic pathway, causing chronic congenital non-spherocytic hemolytic anemia. Clinical severity ranges from mild anemia to transfusion-dependent diseases. Severe neonatal presentations, including liver failure, have rarely been reported. Case presentation: We report a preterm female neonate with PKD who developed early-onset hemolytic anemia, conjugated hyperbilirubinemia, hepatosplenomegaly, coagulopathy, and progressive transaminitis. Imaging demonstrated hepatomegaly with diffuse parenchymal involvement. Whole-genome sequencing identified compound heterozygous pathogenic mutations in the PKLR gene, confirming the diagnosis of PKD. The patient required continuous transfusion support and was discharged following clinical stabilization. Discussion: Although PKD most often manifests as isolated hemolytic anemia, this case illustrates a rare neonatal phenotype with concurrent liver dysfunction. We investigated the potential underlying mechanism. Recognition of hepatic involvement in PKD is essential because liver failure is associated with considerable morbidity and mortality, and it may necessitate interventions such as liver transplantation. Conclusions: This case highlights the importance of considering PKD in neonates presenting with hemolysis and liver failure. Early genetic confirmation enables timely management, including transfusion support, iron overload surveillance, and anticipatory guidance for potential hepatic complications. Full article

Chronic stress is a key risk factor for depression and metabolic dysfunction, widely mediated through oxidative stress and inflammatory pathways. Natural products such as honey are increasingly investigated for their potential to attenuate stress-induced pathophysiological changes. This study evaluated the protective effects of Malaysian Acacia honey (AH) on glucose regulation, oxidative damage, histopathological alterations, and pro-inflammatory cytokine expression in stress-induced rats. Male Sprague–Dawley rats (n = 42) were subjected to chronic unpredictable mild stress and supplemented with AH, amitriptyline (AMT), or their combination for 28 days. Blood glucose levels, erythrocyte hemolysis, histological changes in liver and kidney, and expression of IL-1β and TGF-β1 in ileum, caecum, and hypothalamus were assessed. Data were reported as mean and standard error of mean (SEM) after three or more independent experiments had been conducted. The data were analyzed using a paired-t-test or a one-way or two-way analysis of variance (ANOVA) and considered significant if p < 0.05. Stress markedly elevated glucose levels (7.97 ± 0.20 mmol/L), increased hemolysis (14.30% ± 2.96), and induced hepatic (cytoplasmic vacuolation, 1.40 ± 0.25; cell lining absent, 1.20 ± 0.37) and renal lesions (dilated intertubular capillaries, 1.40 ± 0.51; inflammation, 2.20 ± 0.20), accompanied by upregulation of IL-1β (1.27-fold ± 0.20) and TGF-β1 (1.00-fold ± 0.08). Supplementation with AH significantly reduced hyperglycemia, inhibited hemolysis, ameliorated tissue damage, and downregulated pro-inflammatory cytokines. Combination therapy with AH and AMT produced the most significant improvements near to normal level, suggesting synergistic benefits. These findings highlight the therapeutic potential of AH as a natural adjunct in managing stress-related metabolic and inflammatory disturbances. Full article

The prevalence of advanced heart failure (AdHF) is increasing globally, driven by population aging and improved survival rates in chronic heart failure (CHF). Durable Mechanical Circulatory Support (DMCS), particularly Left Ventricular Assist Devices (LVADs), has become a cornerstone in AdHF management. However, its successful implantation requires a comprehensive preoperative evaluation integrating cardiac, hemodynamic, and systemic assessments. Echocardiography and cardiac magnetic resonance (CMR) provide critical data for risk stratification—e.g., LV ejection fraction < 25%, LV end-diastolic diameter < 60 mm, or free wall RV longitudinal strain (fwRVLS) > −14% predict poorer outcomes. Right heart catheterization (RHC) identifies hemodynamic contraindications (PVR > 6 WU, PAPi < 1.5, cardiac index < 2 L/min/m²), while cardiopulmonary exercise testing (CPET) remains pivotal for assessing functional reserve (peak VO₂ < 12 mL/kg/min or <50% predicted). Systemic assessment must address renal, hepatic, oncologic, and psychiatric comorbidities that influence surgical risk. Integrating these multimodal data within a multidisciplinary framework—spanning cardiologists, cardiac surgeons, anesthesiologists, and psychologists—optimizes selection and outcomes for DMCS candidates. Full article

Background: Obesity is a highly prevalent chronic disease characterized by excessive weight gain and fat accumulation. There is growing evidence that Lactiplantibacillus plantarum strains with bile salt hydrolase (BSH) activity are effective in preventing and alleviating obesity. Methods: Initially, we screened bacterial strains with high hydrolytic activity against glycochenodeoxycholic acid (GDCA), and constructed an isogenic bsh1 knockout mutant. Subsequently, male C57BL/6J mice fed a high-fat diet (HFD) were randomly assigned to receive daily gavage of either the wild-type Lp20 (Lp20-WT) or the bsh1-deficient mutant (Lp20-Δbsh1) for 8 weeks. Serum cholesterol levels and histopathological changes in liver sections were monitored. Hepatic gene expression was quantified by RT-qPCR, and fecal bacterial communities were analyzed via 16S rRNA gene sequencing. These comprehensive assessments aimed to evaluate metabolic improvements and uncover the potential mechanisms behind the observed effects. Results:L. plantarum Lp20 hydrolyzed 91.62% of GDCA, exhibiting the highest bile-salt hydrolase (BSH) activity among tested isolates. Whole-genome sequencing and in-silico analyses mapped this activity to bsh1; gene deletion of bsh1 confirmed the role of bsh1 in GDCA hydrolysis. Daily gavage of the wild-type strain (Lp20-WT) to diet-induced obese mice markedly attenuated weight gain, reduced inguinal white adipose tissue and mesenteric fat mass, and lowered serum TC and LDL-C by 20.8% and 33.3%, respectively, while decreasing ALT and AST levels and reversing hepatic steatosis. In contrast, the bsh1-null mutant (Lp20-Δbsh1) failed to elicit any measurable metabolic benefit. Mechanistically, Lp20-WT upregulated rate-limiting bile-acid synthetic enzymes CYP7A1 and CYP27A1, thereby accelerating the catabolism of cholesterol into bile acids. Concurrently, it activated hepatic TGR5 and FXR signaling axes to modulate hepatic metabolism. Moreover, Lp20-WT restructured the gut microbiota by notably enhancing the abundance of beneficial bacteria such as norank_f__Muribaculaceae, Akkermansia, and Alistipes, while reducing the abundance of potentially harmful taxa, including norank_f__Desulfovibrionaceae, Dubosiella, and Mucispirillum. Conclusions: This study provides direct evidence of BSH’s anti-obesity effects through gene deletion. Specifically, BSH lowers cholesterol by modulating hepatic bile-acid metabolism-related gene expression and altering the gut microbiota composition. However, the study is limited by a small sample size (n = 6), the use of male mice only, and its preclinical stage, indicating a need for further validation across diverse strains and human populations. Full article

Background/Objectives: To investigate the role of hepatobiliary phase (HBP) signal intensity (SI) on Gadoxetic acid (GA)-enhanced liver magnetic resonance imaging (MRI) in improving the diagnostic accuracy of the histological grade of fibrosis in patients with chronic hepatitis B (CHB). Methods: This retrospective study enrolled patients with CHB who underwent biopsies from the highest and lowest intensity areas identified on HBP images obtained from GA-enhanced MRI. The patients were divided into two groups based on segmental SIs: Group 1 (maximum SI) and Group 2 (minimum SI). An ultrasound-guided tru-cut biopsy was performed in these two segments. Forty patients undergoing histopathological examination were included in the study. Group comparisons were examined using Chi-square and independent-sample t-tests, and receiver operating characteristic curve analysis (ROC) was performed to determine the cutoff values of the SI for modified histologic activity index (mHAI) and fibrosis grading. Results: There were no histopathological differences between the groups (p > 0.05), but significant inflammation and fibrosis were observed in hepatic segments with an SI value of <617 (p < 0.001). The ROC results showed that the predictive cutoff value of SI for mHAI and fibrosis grading were 606 (AUC: 0.83, 95% CI 0.737–0.921, p < 0.001) and 599 (AUC: 0.85, 95% CI 0.766–0.935, p < 0.001), respectively. Conclusions: In patients with CHB, performing a biopsy from the liver segment with the lowest SI on GA-enhanced MRI increases the diagnostic accuracy for assessing the histological severity of hepatic inflammation and fibrosis. Full article

Background and Objectives: The Hepatitis E Virus (HEV) is increasingly recognized as a cause of chronic infection in immunocompromised patients, but its precise role in cryptogenic cirrhosis (CC) is unclear. CC is defined as liver cirrhosis in which all known causes, including viral, autoimmune, metabolic, and alcohol-related etiologies, have been meticulously excluded. We aimed to address this gap by definitively assessing HEV’s etiological contribution in CC through seroprevalence comparison and evaluating its long-term prognostic impact on disease progression and adverse clinical outcomes. Materials and Methods: This is a retrospective, single-center, observational, and longitudinal cohort study, conducted between July 2017 and June 2025. The study included 52 CC patients, whose diagnosis was strictly confirmed by excluding all known etiologies, and 900 healthy blood donors from the same region. CC patients were retrospectively followed for five years to assess long-term clinical outcomes. We compared HEV seropositive and seronegative patients for accelerated disease progression (assessed by follow-up MELD-Na scores) and cirrhosis-related death. We employed multivariable logistic regression to adjust for demographic confounders in the prevalence comparison and multivariable COX regression for survival analysis to determine the independent prognostic role of HEV seropositivity. Results: The anti-HEV IgG seroprevalence in CC patients (42.3%) was significantly higher than in healthy donors (12.8%) (p < 0.001). Multivariable logistic regression confirmed CC status as an independent predictor of HEV seropositivity (Adjusted OR = 6.142, p < 0.001). During the five-year follow-up, the cirrhosis-related death rate was significantly higher in the anti-HEV IgG positive group (36.4% vs. 13.4%; p = 0.047), and their follow-up MELD-Na score was significantly higher (p = 0.029). However, multivariable COX analysis did not sustain anti-HEV IgG positivity as an independent risk factor for death (p = 0.294). Conclusions: HEV exposure is independently and significantly higher in CC patients. While anti-HEV IgG positivity correlates with higher mortality and accelerated disease progression in univariable analysis, its lack of independent prognostic significance suggests it may primarily function as a marker for a more advanced stage of CC or underlying immune dysfunction. Further rigorous prospective studies are necessary to precisely define HEV’s long-term prognostic role and evaluate its impact on disease progression. Full article

Background: Typhoid fever (TF) is a systemic infection caused by Salmonella enterica serovar Typhi, typically associated with regions where sanitation and access to clean water are inadequate. Although rare in non-endemic countries, TF remains a diagnostic consideration in travelers returning from endemic areas with febrile illness. Case report: We present the case of an 18-year-old female who developed TF following recent travel to Nigeria. The initial clinical presentation, including fever, dysuria, and abdominal pain, led to a misdiagnosis of acute pyelonephritis. Malaria, arboviral infections, acute viral hepatitis, and parasitic diseases were systematically ruled out through clinical evaluation, serological testing, and parasitological analysis. The clinical course was marked by fever, abdominal pain, somnolence, and hematological and hepatic abnormalities. Blood cultures confirmed the diagnosis, with the isolate verified and serotyped by the National Center of Infectious and Parasitic Diseases. Targeted antimicrobial treatment with ceftriaxone and levofloxacin resulted in full recovery, with no evidence of relapse or chronic carriage over a three-month follow-up period. Conclusions: This case highlights the critical importance of a structured differential diagnostic approach and microbiological confirmation in febrile patients with relevant travel history. In non-endemic settings, where TF may be underrecognized, early recognition, pathogen identification, and appropriate antimicrobial therapy remain essential to favorable outcomes and public health safety. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition globally, driven by strong genetic and environmental components. This review summarizes recent advances in understanding the genetic architecture of MASLD. Genome-wide association studies (GWAS) have identified several key risk variants, primarily in genes such as PNPLA3, TM6SF2, GCKR, and MBOAT7, which influence hepatic lipid metabolism and disease progression. By utilizing surrogate markers of MASLD, researchers have also identified numerous putative MASLD-associated genes, warranting further investigation through functional genomics approaches. Next-generation sequencing techniques have uncovered rare variants in genes like APOB and ABCB4, as well as protective variants in HSD17B13 and CIDEB. This review discusses the potential of polygenic risk scores for disease stratification and the development of genetically informed therapeutic strategies. Additionally, it explores the future of functional genomics approaches in discovering novel treatment strategies. While the evolving genetic landscape of MASLD provides promising insights for precision medicine approaches in diagnosis, prognosis, and treatment, significant translational gaps remain. Addressing these challenges will be critical for realizing the full potential of personalised approaches in clinical management. This review synthesizes these findings and discusses their implications for future research and clinical practice in MASLD. Full article

Chronic hepatitis B virus (HBV) infection is a major health problem that leads to approximately one million deaths every year worldwide. Mother-to-child transmission (MTCT) is the major cause of chronic HBV infection. HBV e antigen (HBeAg) is a secretory viral protein and modulates the immunological landscape of the newborn to promote HBV persistence. HBeAg actively reprograms innate and adaptive immunity. Mechanistically, HBeAg regulates macrophage polarization, suppresses dendritic cell and natural killer (NK) cell activities, impairs T cell and B cell functions, and promotes the expansion of myeloid-derived suppressor cells (MDSCs). These multifaceted effects contribute to immune tolerance and persistent HBV infection in the offspring of carrier mothers. Clinically, HBeAg status is a critical determinant for MTCT risk stratification and intervention, particularly in resource-limited settings. Despite advances in neonatal immunoprophylaxis and maternal antiviral therapy, residual transmission of HBV persists. Emerging approaches targeting HBeAg directly or restoring antiviral immunity offer promising avenues for breaking immune tolerance and achieving HBV elimination. This review summarizes current understanding of HBeAg-mediated immune modulation and highlights strategies that are being used to disrupt MTCT and treat HBV patients. Full article

Background/Objectives: Phosphatidylinositol (PI) species are bioactive lipids implicated in liver fibrogenesis. Hepatitis C virus (HCV) relies on host lipid metabolism for infection. The relationship between serum PI profiles, chronic HCV, and liver injury remains incompletely defined. Methods: Fourteen PI species were quantified by direct flow injection–tandem mass spectrometry (FIA–MS/MS; triple quadrupole) in serum from 178 patients with chronic HCV at three time points: before treatment and at weeks 4 and 12 after starting direct-acting antiviral (DAA) therapy. Results: At baseline, PI 34:1, 36:1, and 36:3 were higher in patients with ultrasound-diagnosed cirrhosis than in those without, whereas PI 38:4, 40:5, and 40:6 were lower. In non-cirrhotic patients, PI 36:3, 36:4, 38:3, 38:4, and 38:5 increased, while PI 40:5 and 40:6 declined at weeks 4 and 12 after therapy start. In cirrhosis, viral cure was not associated with changes in PI species. By the end of therapy, cirrhotic patients showed higher PI 36:3 and lower PI 38:4 than non-cirrhotic patients. Genotype 3a was associated with lower PI 38:3, 38:4, and 38:5; the reduction in PI 38:4 persisted to the end of therapy. Across time points, most PI species did not correlate with routine markers of liver injury or inflammation. Conclusions: HCV cure remodels the serum PI profile in non-cirrhotic patients. These findings suggest that altered PI profiles are primarily linked to HCV infection, supporting a role for PI lipids in viral propagation. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly attracting growing concern around the world. While there has been progress in the development of pharmacologic treatments, lifestyle and dietary interventions remain as the first-line approach for management. This scoping review aimed to identify dietary strategies for managing MASLD and to highlight current research gaps and challenges. Methods: A systematic search of PubMed and Science Direct was conducted up to 10 July 2025, for relevant studies on dietary modifications and MASLD. Data extracted included types of interventions, outcomes related to liver health, and research limitations. Results: Dietary interventions were shown to consistently improve hepatic and metabolic outcomes. In a randomized controlled trial of 12 weeks (n = 259), a Mediterranean diet reduced hepatic steatosis by 39% and improved insulin sensitivity. A calorie-restricted lifestyle program in adults with MASLD (n = 196) reduced liver fat by 25% over 52 weeks. Resistant starch supplementation (n = 200) lowered intrahepatic triglyceride content by 8% through gut microbiome modulation. A pilot RCT of medically tailored meals in cirrhosis (n = 40) reduced ascites symptoms and improved quality of life. Finally, prebiotic supplementation in MASLD (n = 200) lowered systemic inflammation and increased immune-regulating microbes. In contrast, Western dietary patterns and ultra-processed foods were consistently linked to lipotoxicity and inflammation. Conclusions: Dietary interventions remain critical for the management of chronic liver disease and continue to play a vital role even as pharmacotherapy options emerge. Further research should explore precision nutrition and microbiome-based therapies while also addressing the methodological limitations like the underutilization of causal inference frameworks. Finally, it is also important to consider culturally tailored interventions to account for barriers in access and equity in underserved populations. Full article