Liver Disease Research Articles

High-Sensitivity C-Reactive Protein Levels in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Metabolic Alcohol-Associated Liver Disease (MetALD), and Alcoholic Liver Disease (ALD) with Metabolic Dysfunction

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a recently introduced term for steatotic liver disease (SLD). Although the inflammatory process is central to the pathogenesis of SLD, research investigating the differences in systemic inflammation across various SLD subtypes as well as sex differences is limited. This population-based, cross-sectional study investigated the association between SLD subtypes and high-sensitivity C-reactive protein (hs-CRP) levels among Korean adults (N = 20,141; mean age: 50.8 ± 16.7 years). The participants were classified into five groups that included no SLD, MASLD, metabolic alcohol-associated liver disease (MetALD), alcoholic liver disease with metabolic dysfunction (ALD with MD), and other SLDs. The median (Q1, Q3) value of the hs-CRP level was 0.54 mg/L (0.33, 1.04). Among men, compared to levels in the no SLD group, the MASLD, MetALD, and ALD with MD groups were associated with 41.9% (95% confidence interval [CI]: 35.1–49.1%), 46.8% (95% CI: 35.0–59.6%), and 51.8% (95% CI: 30.0–77.2%) increases in hs-CRP levels, respectively. The association between SLD subtypes and hs-CRP levels was stronger among women, and compared to the levels in the no SLD group, the MASLD, MetALD, and ALD with MD groups were associated with 81.5% (95% CI: 73.6–89.8%), 84.3% (95% CI: 58.1–114.8%), and 98.2% (95% CI: 38.0–184.8%) increases in hs-CRP levels, respectively. In conclusion, our findings indicate a varying profile of systemic inflammation across SLD subtypes, with more pronounced increases in hs-CRP levels in women with SLDs.

Trends in Hepatocellular Carcinoma Mortality Rates in the US and Projections Through 2040

ImportanceThe burden of liver cancer varies worldwide. An upward trend in both hepatocellular carcinoma (HCC) incidence and mortality in the past 2 decades has been observed.ObjectiveTo assess observed HCC-related age-standardized mortality rates (ASMRs) in the US for 2006 to 2022 and provide ASMR projections through 2040.Design, Setting, and ParticipantsThis cross-sectional study used data from the National Vital Statistics System, which is accessible through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research website. Data on deaths attributed to HCC (from January 1, 2006, to December 31, 2022) were obtained for adults 25 years or older and were stratified by liver disease etiology, age, sex, and race and ethnicity. Etiologies included alcohol-associated liver disease (ALD), hepatitis B virus (HBV), hepatitis C virus (HCV), and metabolic dysfunction–associated steatotic liver disease (MASLD).Main Outcomes and MeasuresThe main outcomes were (1) observed ASMRs of HCC per 100 000 persons using Joinpoint regression (National Cancer Institute) to assess trends during 2006 to 2022 and (2) ASMRs projected for 2023 to 2040 using Prophet and AutoARIMA modeling.ResultsThis study included 188 280 HCC-related deaths from 2006 to 2022. Most deaths occurred among males (77.4%). The annual percentage change was 4.1% (95% CI, 2.2% to 7.7%) for 2006 to 2009 and decreased to 1.8% (95% CI, 0.7% to 2.0%) for 2009 to 2022, with an overall observed ASMR of 5.03 per 100 000 persons in 2022 and a projected ASMR of 6.39 per 100 000 persons by 2040, with consistent trends for both sexes. By etiology, ASMRs decreased for HCV- and HBV-related mortality but increased for ALD- and MASLD-related mortality. In 2022, MASLD surpassed HBV as the third-leading cause of HCC-related death and was projected to overtake HCV in 2032 as the second-leading cause; ALD was projected to be the leading cause of HCC-related death in 2026. In 2022, the ASMR was higher among individuals aged 65 years or older compared with those aged 25 to 64 years (18.37 vs 1.79 per 100 000 persons). The American Indian or Alaska Native population had the largest increase in projected ASMR by 2040 (14.71 per 100 000 persons) compared with the Asian population (3.03 per 100 000 persons).Conclusions and RelevanceIn this cross-sectional study, ASMRs for ALD- and MASLD-related HCC death increased rapidly from 2006 to 2022; ALD-related HCC was projected to be the leading cause by 2026, with MASLD as the second-leading cause by 2032. These findings may serve as a reference for public health decision-making and timely identification of groups at high risk of HCC death.

Study the role of xanthine oxidase inhibitor, allopurinol in experimentally induced steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease which can lead to cirrhosis and hepatic failure. It is observed in patients with both type 1 and type 2 diabetes mellitus (T1DM, T2DM). Allopurinol, a xanthine oxidase inhibitor that is widely used in clinical practice, has been demonstrated to reduce hepatic oxidative stress and attenuate acute liver injury which may be through activation of antioxidant pathways. This work aimed at investigating the role of Allopurinol (ALP) in attenuation of type 1 diabetes associated with Nonalcoholic fatty liver disease (NAFLD) and exploring the possible molecular mechanism by which ALP attenuates NASH in type 1 diabetes. Forty-five adult male albino rats were included in the study. They were randomly allocated to 3 equal groups: group I (control), Group II (diabetic animals), Group III (diabetic animals with allopurinol treatment). At the end of this experimental study measurements of serum glucose, ALT, AST, cholesterol, triglyceride, serum levels of uric acid, malondialdehyde (MDA), serum superoxide dismutase (SOD) were done. Histological analysis of liver tissue to diagnose steatohepatitis and gene expression of nuclear factor-erythroid-2- related factor-2 (Nrf2) & TNFα were done. Diabetic rates treated with allopurinol (group III) showed decrease in serum levels of ALT, AST, cholesterol, uric acid and MDA compared to diabetic rat group. As regards TNF, gene expression was significantly decreased in group III compared to group II. This study also demonstrated that Nrf2α was significantly increased in group III compared to group II. Allopurinol also, ameliorated the histopathological changes observed in group II. In conclusion, allopurinol treatment increases the Nrf2 gene expression in the liver of STZ-induced diabetic rats and ameliorates steatohepatitis through modulation of TNF-α gene expression. Allopurinol could be a candidate for prevention or treatment of NAFLD.

Classification of Liver Lesion Stages using pyRadiomics Features Combined with 3D-CNN in 3D-CT and US Images

Objectives: The goal of this study is to identify the various stages in liver diseases employing pyRadiomics features by analyzing the 3-dimensional CT and US images. Methods: The study uses Gray level Run Length Matrix for feature extraction and 3D-CNN for classification and compared with methods like Support Vector Machine (SVM), Random Forest (RF), and Naïve Bayes (NB) classifiers to assess the efficiency of the proposed model. The suggested algorithm is implemented using the library functions in Tensorflow and Keras packages in Python. Findings: The study utilizes radiomic feature extraction and two-phase classification to detect and classify liver disorders. In the first phase, binary classification is used to classify US and CT images as normal or abnormal, with accuracy rates of 95.4% and 97.9%. This is followed by the second phase classification, which classifies the lesion stages for both US and CT aberrant images. CT images have been shown to be more accurate in categorizing lesion stages than US imaging. CT images have a much lower misclassification rate at each step than US images. Finally, the effectiveness of the 3D-CNN model is compared with SVM, RF, and NB and the suggested method outperforms the other methods. Novelty: The suggested architecture employs radionics feature extraction with two-phase CNN for classification and the suggested method is found to be more efficient than SVM, RF, and NB. Keywords: Radiomics; Feature Extraction; Convolutional Neural Networks (CNN); Classification; Liver Diseases

Artificial Intelligence and Image Analysis-Assisted Diagnosis for Fibrosis Stage of Metabolic Dysfunction-Associated Steatotic Liver Disease Using Ultrasonography: A Pilot Study

Purpose: Elastography increased the diagnostic accuracy of liver fibrosis. However, several challenges persist, including the widespread utilization of equipment, difficulties in measuring certain cases, and the influence of viscosity factors. A rough surface and a blunted hepatic margin have long been acknowledged as valuable characteristics indicative of hepatic fibrosis. The objective of this study was to conduct an image analysis and quantitative assessment of the contour of the sagittal section of the left lobe of the liver. Methods: Between February and October 2020, 486 consecutive outpatients underwent ultrasound examinations at our hospital. A total of 214 images were manually annotated by delineating the liver contour to create annotation images. U-Net was employed for liver segmentation, with the dataset divided into training (n = 128), testing (n = 42), and validation (n = 44) subsets. Additionally, 43 Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) cases with pathology data from between 2015 and 2020 were included. Segmentation was performed using the program developed in the first step. Subsequently, shape analysis was conducted using ImageJ. Results: Liver segmentation exhibited high accuracy, as indicated by Dice loss of 0.044, Intersection over Union of 0.935, and an F score of 0.966. The accuracy of the classification of the liver surface as smooth or rough via ResNet 50 was 84.6%. Image analysis showed MinFeret and Minor correlated with liver fibrosis stage (p = 0.046, 0.036, respectively). Sensitivity, specificity, and AUROC of Minor for ≥F3 were 0.571, 0.862, and 0.722, respectively, and F4 were 1, 0.600, and 0.825, respectively. Conclusion: Deep learning segmentation of the sagittal cross-sectional contour of the left lobe of the liver demonstrated commendable accuracy. The roughness of the liver surface was correctly judged by artificial intelligence. Image analysis showed the thickness of the left lobe inversely correlated with liver fibrosis stage.

Clustering of hepatitis C infection among family members in Aden, Yemen

Abstract Background Hepatitis C infection is a common cause of liver diseases such as cirrhosis and liver carcinoma. This study aims to determine the clustering of HCV infection among family members of HCV-positive patients (index cases) and the association between internal and external risk factors and HCV infection among these family members. Methods This cross-sectional study was conducted during a period from January to June 2024. One hundred and seventeen family members belonging to 26 index cases were enrolled in this study. Blood samples were collected from all family members, and then sera were separated and tested for anti-HCV antibodies by using a commercially available Cobas technique based on ECLIA. Results Among 117 family members, the majority 55.6% were females. The clustering of HCV infection among family members was 7.7%. The highest rates were 9.6% among males and 11.8% among members who were in close contact with female-positive cases, 12.8% in the age group 20–29 years, and 27.3% among brothers, but there were no HCV-positive cases detected among fathers, daughters, and husbands. There was a significant association between HCV infection and some behaviors of family members such as sharing the same sleeping places, nail clippers, and towels with index cases and exposure to cupping (p = 0.0001, 0.002, 0.017, and 0.050), respectively. Conclusion The HCV infection among family members in Aden, Yemen, was low in comparison with most studies globally. The highest rates were found among males, those in contact with female index cases, in the age group 20–29 years, and brothers as relatives, but there were no positive cases among fathers, husbands, daughters, and other relatives.

Chronic systemic inflammation predicts long-term mortality among patients with fatty liver disease: Data from the National Health and Nutrition Examination Survey 2007–2018

Background Low-grade systemic inflammation (SI) in patients with fatty liver disease (FLD) is an important hallmark of disease onset and progression. This study aims to evaluate the prognostic significance of novel SI markers in FLD. Methods This was a retrospective cohort study. We included adult patients with FLD with complete data and analyzed the association between chronic SI and long-term mortality in patients with FLD. Systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were evaluated based on peripheral blood counts and FLD was determined by the Fatty Liver Index. Results A total of 5497 patients with FLD were included in the final analysis. SII and PIV (but not SIRI) were found to be associated with all-cause and cardiovascular mortality in univariate analysis. Multivariate Cox regression analysis and KM analysis demonstrated that SII and PIV were associated with all-cause mortality, with SII showing a nonlinear correlation in RCS. PIV (but not SII) was associated with the cardiovascular-related survival probability over time. Stratified analysis indicated that the positive correlation between SII and PIV and all-cause mortality was not altered by subgroups. Conclusions SII and PIV are strongly and consistently associated with all-cause mortality in patients with FLD, with PIV potentially showing a closer association with cardiovascular mortality.

Benefits of Astaxanthin supplementation: selected issues

INTRODUCTION: Astaxanthin, a carotenoid compound belonging to the xanthophyll group, occurs naturally in algae, yeast, and marine organisms such as shrimp, trout, lobster, and krill. Renowned for its antioxidant prowess, astaxanthin shields mitochondria from harm caused by reactive oxygen species (ROS). Its exceptional antioxidant potency is noteworthy, surpassing that of α-tocopherol (Vitamin E) by 100-fold and eclipsing over 600 other recognized natural carotenoids. REVIEW METHODS: The article was complied by analyzing data from PubMed and Google Scholar data regarding the benefits of astaxanthin supplementation. THE STATE OF KNOWLEDGE: Astaxanthin, offers a range of health benefits. It modulates immune responses, inhibits cancer cell growth, reduces bacterial presence and gastric inflammation. With potent antioxidant properties, it also serves as a neuroprotective agent by combating neuroinflammation. Additionally, astaxanthin shows promise in preventing and treating liver diseases, thanks to its antioxidant, anti-inflammatory, and signaling pathway regulation properties. Overall, antioxidants like astaxanthin, whether from diet or supplements, help combat lipid and protein oxidation, thereby slowing down the progression of atherosclerosis. CONCLUSION: Astaxanthin emerges as a promising candidate for treating various pathological conditions linked to oxidative damage and impaired mitochondria function. These conditions span across cardiovascular diseases, neurodegenerative disorders and liver diseases. It could also help healthy people like athletes in enhancement of overall quality of life.

Abstract C015: IL-27R signaling modulates protective versus pathogenic T cell responses in hepatocellular carcinoma

Abstract Liver cancer is the 3rd leading cause of cancer death. Hepatocellular carcinoma (HCC) is the major form of primary liver cancer, with a growing incidence rate estimated to surge by 50% in the coming twenty years. Although some success has been achieved with immune checkpoint blockade inhibitors, many HCC patients do not respond well to the treatments. Therefore, it is critical to better understand immune mechanisms regulating HCC to identify new biomarkers and develop novel immunotherapies for HCC patients. HCC is driven by chronic liver diseases and is frequently associated with chronic inflammation in the liver. Cytokines are small mediators of inflammation that play an essential role in inflammatory diseases and tumorigenesis. IL27 is a member of the IL6/IL12 superfamily with context-dependent roles in various inflammatory disorders and cancer. IL27 receptor (R) is expressed by most immune cells and several non-immune cells and plays pivotal roles in the regulation of immune responses. Recent work from our lab shows that IL27R signaling suppresses anti-cancer immune response in HCC, acting via the control of innate cytotoxic cells, and Il27ra -/- mice develop significantly less HCC. However, how IL27R signaling regulates T cell subsets in HCC in vivo remains elusive. Here, using diethylnitrosamine (DEN)-induced mouse model of HCC we found a reduction of regulatory T cells (Tregs) in tumor-bearing Il27ra-/-mice along with lowered HCC burden. ScRNA sequencing of CD45+ cells isolated from HCC tumors indicated a less proliferative phenotype of Tregs and more cytotoxic and less exhausted CD8 T cells in mice with Il27ra deficiency. Pathway analysis suggested that IL27R-deficient Tregs were more quiescent, as characterized by the downregulation of various metabolic pathways. Our newly generated Foxp3 cre Il27ra flox mice show a significant reduction of DEN-driven HCC accompanied by an increase of tumor-infiltrating activated CD8 T cells compared to IL27R sufficient controls. Treg-specific deletion of IL27R caused the upregulation of TCF1 in Tregs which has been recently demonstrated to control Treg immune-suppressive functions in colorectal cancer. Meanwhile, tumor-infiltrating effector CD8 T cells were increased in Foxp3 cre+ Il27ra flox mice relative to their Foxp3 cre- Il27ra flox littermate controls. Interestingly, CD8 T cell specific deletion of IL27R did not impact HCC growth in CD8 cre Il27ra flox mice. Overall, our data suggest that IL27R signaling suppresses anti-HCC immunity by enhancing the pro-tumorigenic Tregs and suppressing anti-tumor effector CD8 T cell functions. Citation Format: Zhengzheng Shi, Jiani Zhu, Aleksandra Mazitova, Anastasiia Marchenko, Sergei Grivennikov, Ekaterina Koltsova. IL-27R signaling modulates protective versus pathogenic T cell responses in hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C015.

ACBP/DBI neutralization for the experimental treatment of fatty liver disease.

Acyl-CoA binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular checkpoint of autophagy. Here, we report that patients with histologically confirmed metabolic-associated steatohepatitis (MASH) or liver fibrosis exhibit elevated levels of circulating ACBP/DBI protein as compared to non-affected controls. Plasma ACBP/DBI strongly correlated with the NAFLD and FIB4 scores in patients, and these correlations were independent of age and body mass index. We studied the capacity of a monoclonal antibody (mAb) neutralizing mouse ACBP/DBI to combat active liver disease in several mouse models, in which steatohepatitis had been induced by four different protocols, namely, (i) methionine/choline-deficient diet, (ii) Western style diet (WD) alone, (iii) WD combined with the hepatotoxic agent CCl4, and (iv) a combination of CCl4 injections and oral ethanol challenge. Injections of anti-ACBP/DBI mAb attenuated histological, enzymological, metabolomic and transcriptomic signs of liver damage in these four models, hence halting or reducing the progression of non-alcoholic and alcoholic liver disease. Steatosis, inflammation, ballooning and fibrosis responded to ACBP/DBI inhibition at the preclinical level. Altogether, these findings support a causal role of ACBP/DBI in MASH and liver fibrosis, as well as the possibility to therapeutically target ACBP/DBI.

Time-course RNA sequencing reveals high similarity in mRNAome between hepatic stellate cells activated by agalactosyl IgG and TGF-β1.

Previous studies have demonstrated the clinical relevance of aberrant serum immunoglobulin G (IgG) N-glycomic profiles in liver fibrosis and the pathogenic effects of agalactosyl IgG on activating hepatic stellate cells (HSCs). However, the dynamics of gene expression changes during HSC activation by agalactosyl IgG remain poorly understood. We performed RNA sequencing to analyze the mRNAome of human LX-2 HSCs at multiple time points after treatment with agalactosyl IgG and then compared these results with those obtained after normal IgG and transforming growth factor (TGF)-β1 treatments. Gene expression changes were significantly pronounced on day 5 and subsided by day 11 after HSC activation. A high degree of similarity in gene expression patterns between HSCs treated with agalactosyl IgG and TGF-β1 was observed, of which 1796 and 1785 differentially expressed genes (DEGs) were identified, respectively. Disease ontology analyses revealed that 114 and 105 DEGs in activated HSCs following agalactosyl IgG and TGF-β1 treatments, respectively, were linked to liver cirrhosis, hepatitis, fatty liver disease, hepatitis B, and alcoholic hepatitis, with CCL5 and FAS being the most commonly affected genes. DEGs associated with liver fibrosis or aforementioned liver diseases involved in gene annotation, physiological functions, and signaling pathways regarding secretion of cytokines and chemokines, expression of fibrosis-related growth factors and their receptors, modification of extracellular matrices, and regulation of cell viability in activated HSCs. In conclusion, this study characterized the dynamics of mRNAome and gene networks and identified the liver fibrosis-related DEGs during HSC activation by agalactosyl IgG and TGF-β1.

Can Talaromyces marneffei Infection Cause Acute Liver Failure? A Case Report

Introduction: Talaromyces marneffei is a pathogen that causes talaromycosis, a systemic fungal infection. Cases in which hepatic failure is the primary clinical presentation are exceedingly rare. Case Presentation: This report details the case of a 49-year-old male with no prior liver disease, presenting to the hospital with persistent symptoms, including a fever lasting over ten days, abdominal distension for five days, and jaundice for three days. The patient’s history included immune thrombocytopenia and prolonged glucocorticoid therapy. Physical examination revealed yellowing of the skin and sclera, abdominal distension, firmness of the abdominal wall, absence of abdominal tenderness, positive shifting dullness, and pitting edema in the lumbosacral region and bilateral lower extremities. An HIV antibody test was negative. The patient developed hepatic failure and received artificial liver support along with routine therapy. Despite these interventions, the patient was automatically discharged without improvement and subsequently passed away. Post-discharge, cultures from pleural and abdominal effusions identified Talaromyces marneffei. Conclusions: Talaromyces marneffei infection should be considered in the differential diagnosis of immunocompromised patients, particularly those with no history of liver disease but with long-term glucocorticoid or immunosuppressant use who present with acute liver failure. Early and aggressive investigation for the causative pathogen is essential to minimize diagnostic and treatment delays. Given the prolonged incubation period of Talaromyces marneffei, metagenomic next-generation sequencing may offer a more rapid approach for etiological diagnosis.

Occupational stress trajectories and metabolic dysfunction-associated steatotic liver disease among female nurses: a prospective Cohort Study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prominent cause of chronic liver disease, and occupational stress may serve as a potential risk factor. This study aims to assess the association between occupational stress trajectories and incident MASLD among Chinese female nurses. We conducted a prospective longitudinal study using data from the Nurse' Health Cohort Study, involving 1,113 female nurses, free of MASLD at baseline (2018). Occupational stress was measured using the Chinese Nurse Job Stress Scale at four time points. Group-based trajectory modeling was used to identify distinct stress trajectories. Through doctors' diagnoses, we assessed incident MASLD over a subsequent 6-year period from 2019 to 2024. Cox proportional hazards regression models evaluated the association of stress trajectories and MASLD risk, adjusting for demographics, work-related factors, and medical conditions. During follow-up, 256 nurses reported incident physician-diagnosed MASLD. Three occupational stress trajectories were identified: moderate decreasing (36.4%), moderate stable (55.9%), and moderate increasing (7.7%). Participants in the moderate increasing stress trajectory had a significantly higher risk of developing MASLD (adjusted HR: 3.14, 95% CI: 2.19-4.49, p < .001) compared to those in the moderate stable trajectory. This association between stress trajectory and MASLD risk was not modified by age or BMI (pinteraction>0.50). The study concludes that increasing stress levels over time are associated with a higher incidence of MASLD. These findings underscore the importance of stress management interventions in reducing the risk of MASLD progression. Further research is needed to explore the underlying mechanisms and to develop targeted strategies for stress reduction in clinical settings.

Predicting Chronic Liver Disease and Jaundice Detection an Integrated Approach Using Statistical Feature Extraction and Machine Learning Algorithms

An important health concern with chronic liver disease is early identification, which is essential for management and therapy. This work suggests an integrated method to identify tattoo-induced jaundice and forecast chronic liver disease by combining statistical feature extraction with machine learning techniques. First, we use statistical techniques based on projections to extract pertinent aspects from patient data, such as test results and clinical markers. We then use Artificial Neural Networks (ANN), KNN, and Naive Bayes to categorize individuals according to the probability that they have chronic liver illness and to pinpoint jaundice episodes associated with tattooing. The KNN technique offers interpretability, managing categorical data is made simple by Naive Bayes, and complicated patterns are captured by ANN using layers of neural networks. These models' performance is assessed using the following metrics: F1 score, recall, accuracy, and precision. Our research aims to improve prediction accuracy and offer practical advice for early diagnosis and individualized treatment plans. By utilizing advanced data analysis and machine learning instruments, the integrated strategy shows promise in enhancing healthcare outcomes.

Effectiveness of flaxseed consumption and fasting mimicking diet on anthropometric measures, biochemical parameters, and hepatic features in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): a randomized controlled clinical trial.

Although benefits of flaxseed and fasting mimicking diet (FMD), each alone, have been shown in the management of metabolic dysfunction-associated steatotic liver disease (MASLD), the benefit of combining the two is not clear. This study aimed to investigate the effect of the combination of FMD and flaxseed supplementation on surrogate measures of MASLD. The present study was conducted as a randomized, parallel, open-label controlled clinical trial on a hundred patients with MASLD for 12 weeks. Eligible participants were assigned to four groups including control group (lifestyle modification recommendations); flaxseed group (30 g/day of flaxseed powder consumption); FMD group (16 h of fasting per day), and combination of FMD with flaxseed. Changes in anthropometric parameters, serum levels of lipids, glycemic measures, High-sensitivity C-reactive protein (hs-CRP), and liver enzymes, and hepatic steatosis and fibrosis by transient elastography were assessed. Serum triglycerides, total cholesterol, fasting blood glucose and insulin, hs-CRP and liver enzymes decreased in all intervention groups. Hepatic steatosis score decreased in the intervention groups, but not significantly in comparison to the control group. Hepatic fibrosis score decreased significantly in the intervention groups compared to control. Our data indicate that the combination of FMD with flaxseed consumption is not superior to either of the interventions alone in the management of MASLD.

Circulating microRNA panels in subjects with metabolic dysfunction-associated steatotic liver disease after following a 2-year dietary intervention.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) affects one-third of the global population. Despite its high prevalence, there is a lack of minimally non-invasive diagnostic methods to assess this condition. This study explores the potential of circulating microRNAs (miRNAs) as diagnostic biomarkers for MASLD after a 2-year nutritional intervention. Fifty-five subjects with steatosis (MASLD group) from the Fatty Liver in Obesity (FLiO) study (NCT03183193) were analyzed at baseline and after 6, 12 and 24 months. Participants were classified into two groups: those who still had steatosis after the intervention (unhealthy group) and those in whom steatosis had disappeared (healthy group). Hepatic status was evaluated through magnetic resonance imaging (MRI), ultrasonography, elastography and serum transaminases. Circulating miRNA levels were measured by RT-PCR. The dietary intervention was able to modulate the expression of circulating miRNAs after 6, 12, and 24 months. Logistic regression analyses revealed that the most effective panels for diagnosing whether MASLD has disappeared after the nutritional intervention included miR15b-3p, miR126-5p and BMI (AUC 0.68) at 6 months, miR29b-3p, miR122-5p, miR151a-3p and BMI (AUC 0.85) at 12 months and miR21-5p, miR151a-3p and BMI at 24 months (AUC 0.85). Circulating miRNAs were useful in predicting MASLD in subjects with overweight or obesity after following a weight-loss oriented nutritional intervention. These findings highlight the potential role of miRNAs in diagnosing MASLD and underscore the importance of precision nutrition in managing and determining MASLD. Trial registration number: NCT03183193 (www. gov).

Effects of multidisciplinary therapy on energy balance, inflammation, and metabolic diseases in adolescents with obesity: A narrative review.

Obesity is a consequence of multiple factors, including genetics, lifestyle and nutritional choices, physical activity, sleep duration, screen time, and mood disorders. These behavioral elements can impair the regulation of energy balance and obesity management that link obesity to a constellation of chronic conditions that lead to a high prevalence of cardiometabolic risk factors, metabolic syndrome, and nonalcoholic fatty liver disease. Multidisciplinary therapy is defined as an approach delivered by a multidisciplinary-trained health team covering at least two components of behavior, physical activity/exercise, dietary habits, and/or psychological counseling associated with clinical interventions. This narrative review summarizes the effects of multidisciplinary therapy on neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, metabolic syndrome, nonalcoholic fatty liver diseases, behavior, and quality of life. We found that multidisciplinary therapy, including medical, nutritional, exercise, and behavioral counseling, and/or education, was useful for addressing outcomes such as visceral adiposity, neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, nonalcoholic fatty liver disease, and metabolic syndrome. The effects were mediated by improvements in neuroendocrine regulation of energy balance, downregulation of the pro-inflammatory states, and a reduction in comorbidities. Multidisciplinary therapy also improved mood disorders and quality of life.

Results of monitoring probable cases of acute severe hepatitis of unknown etiology in children in Мoscow in 2022

In the spring 2022, the number of cases of severe acute hepatitis of unknown etiology was unusual increased in Europe. As an immediate response, the World health organization recommended active efforts to identify such cases at the international level. For monitoring of acute hepatitis in Moscow, patients with suspected liver disease were sent to Infectious Diseases Clinical Hospital No. 1. The goal: study of the structure of diseases occurring with liver damage in children hospitalized in 2022. Materials and methods: analysis of medical records of children hospitalized with a diagnosis of hepatitis from May 1 to December 31, 2022. Еpidemiological data (age, gender, parenteral manipulations, contacts with patients, travel abroad), clinical (fever, jaundice, etc.), laboratory parameters were assessed. Results: A total of 164 completed cases of hepatitis in children aged 5 months to 17 years were analyzed. 36 children met the criteria for probable severe acute hepatitis of unknown etiology. Age median was 7 years [2.25;11]. Girls made up more than half (21 (58.3%). Non-infectious genesis was established in 15 (41.6%). The infectious disease was verified in 11 (30.5%), of which adenoviral infection was detected in 2 children. In 9 (25%) children the etiology of hepatitis was not established. Conclusion. Various infectious and non-infectious diseases among hospitalized children lead to a significant increase in liver transaminases. Most acute hepatitis with unspecified etiology proceeded as an acute infectious disease and ended in recovery. The role of adenoviruses in the development of severe hepatitis in children was not confirmed in our study.

Prior metabolic and bariatric surgery is an independent determinant of severity of decompensation in alcohol-associated liver disease.

Patients with a history of metabolic and bariatric surgery (MBS) are susceptible to developing alcohol use disorder, potentially resulting in end-stage liver disease, with a paucity of data on the evolution of cirrhosis. Our aim was to describe the demographics and mortality in hospitalizations over time in individuals diagnosed with cirrhosis due to alcohol-associated liver disease (ALD) in relation to prior MBS. We included patients hospitalized at the Ghent University Hospital between 1/1/2010 and 01/09/2023 with cirrhosis due to ALD. Data were retrieved retrospectively from all hospitalizations. 46/275 (16.7%) of individuals with cirrhosis admitted with ALD had a history of MBS; they were predominantly female (76.1%), in contrast to the non-MBS population (29.7%) (p<0.0001) and were significantly younger at the time of diagnosis (46 vs. 58years, p<0.0001). Liver disease evolved at a faster pace in the MBS group with a shorter time to first hospitalization (5 vs. 13months, p=0.036), and consecutive hospitalizations. The proportion with primary hospitalization due to acute-on-chronic liver failure (ACLF) was significantly larger in the MBS group (60.9% vs. 27.6%, p<0.0001), and throughout the following hospitalizations, ACLF remained more prevalent in the MBS group. Modeled transplant-free survival was lower in the MBS group (p=0.004), with ACLF as the main cause of death. The weekly amount of alcohol consumed during drinking periods and duration of use were significantly lower in the MBS group. MBS patients hospitalized with ALD develop acute decompensation at a faster pace, with more overall ACLF hospitalizations, and higher cumulative mortality, despite being 12years younger on average. Not applicable.

Evaluating the roles of microRNAs associated with nonalcoholic fatty liver disease in hepatocellular carcinoma tumorigenesis: a systematic review and network analysis

IntroductionNon-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with high morbidity and mortality. The rapidly increasing incidence of NAFLD is becoming an essential precursor of HCC globally. MicroRNAs (miRNAs) are involved in the progression of NAFLD and HCC.MethodPotential miRNAs associated with NAFLD in HCC tumorigenesis were identified through a systematic review, and their roles were evaluated by data mining analysis. The biological function of the potential miRNA and its target genes in NAFLD and HCC were evaluated by bioinformatic analysis.ResultMIR122 was identified as the potential miRNA associated with NAFLD and HCC. Then, MIR122 expression was significantly lower in HCC patients, and higher MIR122 levels were associated with significantly better overall survival. Next, the biological functions of MIR122 and target genes were predicted to be involved in inflammation, fibrosis, cell proliferation, invasion, metastasis, and apoptosis. In particular, the FOXO signaling pathway may regulate the above biological functions.ConclusionMIR122 was suggested to be involved in progressing from NAFLD to HCC through the PI3K/AKT/FOXO pathway.Systematic review registrationPROSPERO, identifier: CRD 42024517940.