Prevalence Of Chronic Liver Disease Research Articles

Metabolic dysfunction-associated steatotic liver disease has become the most common cause of hepatocellular carcinoma in Sweden: A nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, and can lead to hepatocellular carcinoma (HCC), a leading cause of cancer-related death. We aimed to determine the extent to which MASLD is an increasing cause of HCC in Sweden and to determine clinical characteristics associated with underlying MASLD. Using the Swedish quality registry for liver cancer (SweLiv), we identified all adults with a diagnosis of HCC in Sweden between 2012 and 2018. Baseline data were retrieved from SweLiv and other nationwide registers. Totally, 3494 patients with HCC were identified. Of them, 757 patients (22%) had MASLD-HCC. The proportion with MASLD-HCC increased from 19% in 2012 to 25% in 2018 (ptrend = 0.012), and MASLD was since 2017 the leading cause of HCC, surpassing hepatitis C. MASLD was the fastest growing cause of HCC with a 33% increment during the study period. Compared to other patients with HCC, those with MASLD-HCC were older (75 vs. 67 years, p < .001), less commonly had cirrhosis (61% vs. 82%, p < .001), had larger tumours (median 5.5 vs. 4.3 cm, p < .001), and more often extrahepatic metastasis (22% vs. 16%, p < .001). Patients with HCC caused by MASLD or by other causes were equally likely to be diagnosed in an early stage (Barcelona Clinic Liver Cancer 0-A, 27% vs. 30%, p = .129). MASLD is now the leading cause of HCC in Sweden.

Silibinin Targeting Heat Shock Protein 90 Represents a Novel Approach to Alleviate Nonalcoholic Fatty Liver Disease by Simultaneously Lowering Hepatic Lipotoxicity and Enhancing Gut Barrier Function.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological condition characterized by intrahepatic ectopic steatosis. Due to the increase in high-calorie diets and sedentary lifestyles, NAFLD has surpassed viral hepatitis and become the most prevalent chronic liver disease globally. Silibinin, a natural compound, has shown promising therapeutic potential for the treatment of liver diseases. Nevertheless, the ameliorative effects of silibinin on NAFLD have not been completely understood, and the underlying mechanism is elusive. Therefore, in this study, we used high-fat diet (HFD)-induced mice and free fatty acid (FFA)-stimulated HepG2 cells to investigate the efficacy of silibinin for the treatment of NAFLD and elucidate the underlying mechanisms. In vivo, silibinin showed significant efficacy in inhibiting adiposity, improving lipid profile levels, ameliorating hepatic histological aberrations, healing the intestinal epithelium, and restoring gut microbiota compositions. Furthermore, in vitro, silibinin effectively inhibited FFA-induced lipid accumulation in HepG2 cells. Mechanistically, we reveal that silibinin possesses the ability to ameliorate hepatic lipotoxicity by suppressing the heat shock protein 90 (Hsp90)/peroxisome proliferator-activated receptor-γ (PPARγ) pathway and alleviating gut dysfunction by inhibiting the Hsp90/NOD-like receptor pyrin domain-containing 3 (NLRP3) pathway. Altogether, our findings provide evidence that silibinin is a promising candidate for alleviating the "multiple-hit" in the progression of NAFLD.

Si-Wu-Tang alleviates metabolic dysfunction-associated fatty liver disease by inhibiting ACSL4-mediated arachidonic acid metabolism and ferroptosis in MCD diet-fed mice

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear.MethodsFirst, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients.ResultsSerological and hepatic histopathological findings indicated SWT's discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA β-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD.ConclusionIn conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications.Graphical

Envisioning how to advance the MASH field.

Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has ledto, among others, the approval of the first drug specific for metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis). Despite substantial progress, MASLD is still a leading cause of advanced chronic liver disease, including primary liver cancer. This Perspective contextualizes the nomenclature change from nonalcoholic fatty liver disease to MASLD and proposes important considerations to accelerate further progress in the field, optimize patient-centric multidisciplinary care pathways, advance pharmacological, behavioural and diagnostic research, and address health disparities. Key regulatory and other steps necessary to optimize the approval and access to upcoming additional pharmacological therapeutic agents for MASH are also outlined. We conclude by calling for increased education and awareness, enhanced health system preparedness, and concerted action by policy-makers to further the public health and policy agenda to achieve at least parity with other non-communicable diseases and to aid in growing the community of practice to reduce the human and economic burden and end the public health threat of MASLD and MASH by 2030.

A compact breath breathalyzer for identifying the non-alcoholic fatty liver disease biomarker

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease worldwide. Currently, its diagnosis relies primarily on imaging and histological examinations, which are invasive and prone to misdiagnosis in the early stage. To address these limitations, detection and analysis of volatile organic compounds (VOCs) in human breath can be a rapid and non-invasive screening method for NAFLD. In this study, a compact breath breathalyzer was developed, utilizing a miniaturized gas chromatography chip with the STM32 microcontroller as the main control chip to manage airflow, temperature, and receive terminal signals from the photoionization detector. In the experiment, a gas mixture comprising five VOCs (pentane, acetone, toluene, octane, and decane) was selected as the simulated typical disease biomarkers in human breath to investigate the breathalyzer's performance and optimize testing conditions for multi-polar and wide-boiling-range breath samples. Results show that the breathalyzer can detect low-boiling components (< 100°C) such as the isoprene and acetone, with a detection limit less than 50 ppb which are two commonly biomarkers of NAFLD. Furthermore, breath samples were collected from 35 non-diseased individuals, and NAFLD early-stage patient samples were simulated by increasing the isoprene concentration by 10 ppb. Convolutional neural network (CNN) were used to identify the VOC signatures in gas chromatograms with predictive accuracy of 85% for the classification model. Therefore, the compact breath breathalyzer has potential application in the rapid and early screening of NAFLD.

Clinical and endoscopic characteristics of patients undergoing gastrointestinal endoscopic procedures in Egypt: a nationwide multicenter study

BackgroundEgypt faces a significant public health burden due to chronic liver diseases (CLD) and peptic ulcer disease. CLD, primarily caused by Hepatitis C virus (HCV) infection, affects over 2.9% of the population nationwide, with regional variations. Steatotic liver disease is rapidly emerging as a significant contributor to CLD, especially in urban areas. Acid-related disorders are another widespread condition that can significantly impact the quality of life. These factors and others significantly influence the indications and findings of gastrointestinal endoscopic procedures performed in Egypt.AimWe aimed to evaluate the clinico-demographic data, indications, and endoscopic findings in Egyptian patients undergoing gastrointestinal endoscopic procedures in various regions of Egypt.MethodsThis study employed a retrospective multicenter cross-sectional design. Data was collected from patients referred for gastrointestinal endoscopy across 15 tertiary gastrointestinal endoscopy units in various governorates throughout Egypt.Results5910 patients aged 38–63 were enrolled in the study; 75% underwent esophagogastroduodenoscopy (EGD), while 25% underwent a colonoscopy. In all studied patients, the most frequent indications for EGD were dyspepsia (19.5%), followed by hematemesis (19.06%), and melena (17.07%). The final EGD diagnoses for the recruited patients were portal hypertension-related sequelae (60.3%), followed by acid-related diseases (55%), while 10.44% of patients had a normally apparent endoscopy. Male gender, old age, and the presence of chronic liver diseases were more common in patients from upper than lower Egypt governorates. Hematochezia (38.11%) was the most reported indication for colonoscopy, followed by anemia of unknown origin (25.11%). IBD and hemorrhoids (22.34% and 21.86%, respectively) were the most prevalent diagnoses among studied patients, while normal colonoscopy findings were encountered in 18.21% of them.ConclusionThis is the largest study describing the situation of endoscopic procedures in Egypt. our study highlights the significant impact of regional variations in disease burden on the utilization and outcomes of GI endoscopy in Egypt. The high prevalence of chronic liver disease is reflected in the EGD findings, while the colonoscopy results suggest a potential need for increased awareness of colorectal diseases.

Crosstalk in extrahepatic and hepatic system in NAFLD/NASH.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease globally. Non-alcoholic steatohepatitis (NASH) represents an extremely progressive form of NAFLD, which, without timely intervention, may progress to cirrhosis or hepatocellular carcinoma. Presently, a definitive comprehension of the pathogenesis of NAFLD/NASH eludes us, and pharmacological interventions targeting NASH specifically remain constrained. The aetiology of NAFLD encompasses a myriad of external factors including environmental influences, dietary habits and gender disparities. More significantly, inter-organ and cellular interactions within the human body play a role in the development or regression of the disease. In this review, we categorize the influences affecting NAFLD both intra- and extrahepatically, elaborating meticulously on the mechanisms governing the onset and progression of NAFLD/NASH. This exploration delves into progress in aetiology and promising therapeutic targets. As a metabolic disorder, the development of NAFLD involves complexities related to nutrient metabolism, liver-gut axis interactions and insulin resistance, among other regulatory functions of extraneous organs. It further encompasses intra-hepatic interactions among hepatic cells, Kupffer cells (KCs) and hepatic stellate cells (HSCs). A comprehensive understanding of the pathogenesis of NAFLD/NASH from a macroscopic standpoint is instrumental in the formulation of future therapies for NASH.

An integrated network pharmacology approach reveals that Ampelopsis grossedentata improves alcoholic liver disease via TLR4/NF-κB/MLKL pathway

BackgroundAlcohol-related liver damage is the most prevalent chronic liver disease, which creates a heavy public health burden worldwide. The leaves of Ampelopsis grossedentata have been considered a popular tea and traditional herbal medicine in China for more than one thousand years, and possess anti-inflammatory, antioxidative, hepatoprotective, and antiviral activities. PurposeWe explored the protective effects of Ampelopsis grossedentata extract (AGE) against chronic alcohol-induced hepatic injury (alcoholic liver disease, ALD), aiming to elucidate its underlying mechanisms. MethodsFirstly, UPLC-Q/TOF-MS analysis and network pharmacology were used to identify the constituents and elucidate the potential mechanisms of AGE against ALD. Secondly, C57BL/6 mice were pair-fed the Lieber-DeCarli diet containing either isocaloric maltodextrin or ethanol, AGE (150 and 300 mg/kg/d) and silymarin (200 mg/kg) were administered to chronic ethanol-fed mice for 7 weeks to evaluate the hepatoprotective effects. Serum biochemical parameters were determined, hepatic and ileum sections were used for histologic examination, and levels of inflammatory cytokines and oxidative stress in the liver were examined. The potential molecular mechanisms of AGE in improving ALD were demonstrated by RNA-seq, Western blotting analysis, and immunofluorescence staining. ResultsTen main constituents of AGE were identified using UPLC-Q/TOF-MS and 274 potential ALD-related targets were identified. The enriched KEGG pathways included Toll-like receptor signaling pathway, NF-κB signaling pathway, and necroptosis. Moreover, in vivo experimental studies demonstrated that AGE significantly reduced serum aminotransferase levels and improved pathological abnormalities after chronic ethanol intake. Meanwhile, AGE improved ALD in mice by down-regulating oxidative stress and inflammatory cytokines. Furthermore, AGE notably repaired damaged intestinal epithelial barrier and suppressed the production of gut-derived lipopolysaccharide by elevating intestinal tight junction protein expression. Subsequent RNA-seq and experimental validation indicated that AGE inhibited NF-κB nuclear translocation, suppressed IκB-α, RIPK3 and MLKL phosphorylation and alleviated hepatic necroptosis in mice. ConclusionIn this study, we have demonstrated for the first time that AGE protects against alcoholic liver disease by regulating the gut-liver axis and inhibiting the TLR4/NF-κB/MLKL-mediated necroptosis pathway. Therefore, our present work provides important experimental evidence for AGE as a promising candidate for protection against ALD.

Role of CENPF and NDC80 in the rehabilitation nursing of hepatocellular carcinoma and cirrhosis: An observational study.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally and often develops on the foundation of chronic liver disease or cirrhosis. Cirrhosis is a clinically prevalent chronic progressive liver disease characterized by diffuse liver damage resulting from long-term or repeated actions of 1 or more etiological factors. However, the impact of CENPF and nuclear division cycle 80 (NDC80) genes on rehabilitation nursing of HCC and cirrhosis remains unclear. HCC and cirrhosis datasets GSE63898 and GSE89377 profile files were downloaded from the gene expression omnibus database generated on platforms GPL13667 and GPL6947, respectively. Differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), construction and analysis of protein-protein interaction (PPI) networks, functional enrichment analysis, gene set enrichment analysis (GSEA), survival analysis, immune infiltration analysis, and comparative toxicogenomics database (CTD) analysis were conducted. Gene expression heatmaps were plotted. miRNAs regulating central DEGs were selected through TargetScan. A total of 626 DEGs were identified. According to gene ontology (GO) analysis, they were primarily enriched in small molecule metabolic processes, drug metabolic processes, binding of identical proteins, and lipid metabolic processes. Kyoto Encyclopedia of Gene and Genome (KEGG) analysis results indicated that the target genes were mainly enriched in metabolic pathways, phagosomes, glycine, serine, and threonine metabolism. The construction and analysis of the PPI network revealed 3 core genes (NDC80, CENPF, RRM2). Gene expression heatmaps showed that core genes (CENPF, NDC80) were highly expressed in HCC and cirrhosis samples. CTD analysis found that 2 genes (CENPF and NDC80) were associated with liver, jaundice, ascites, fever, dyspepsia, and hepatic encephalopathy. CENPF and NDC80 are highly expressed in HCC and cirrhosis, and CENPF and NDC80 might be the biomarkers of rehabilitation nursing of HCC and cirrhosis.

Novel blood and tissue-based mitochondrial D-loop mutations detected in an Iranian NAFLD patient cohort

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease characterized by an elusive etiology. In its advanced stages, this condition can pose life-threatening implications. Mitochondrial dysfunction due to its impact on hepatic lipid homeostasis, cytokine release, ROS production, and cell death, contributes to the pathogenesis of NAFLD. Previous research reveals a direct link between NAFLD genetic predictors and mitochondrial dysfunction. The emphasis on the D-loop stems from its association with impaired mtDNA replication, underscoring its crucial role in NAFLD progression. We included 38 Iranian NAFLD patients (comprising 16 patients with non-alcoholic fatty liver [NAFL] and 22 patients with non-alcoholic steatohepatitis [NASH]), with matched blood and liver tissue samples collected from each to compare variations in the mitochondrial D-loop sequence within samples. The mitochondrial DNA (mtDNA) D-loop region was amplified using PCR, and variations were identified through sequencing. The resultant sequences were compared with the reference sequence of human mtDNA available in the MITOMAP Database for comparative analysis. In this study, 97 somatic mutations in the mtDNA D-loop region were identified in NAFLD patients. Our study revealed significant difference between the NAFLD patients and control group in 13 detected mutations (P ≤ 0.05). Novel mutations were discovered in hepatic tissues, while mutation 16220-16221ins C was found in both tissues and blood. A significant difference was found in the distribution of D310 and mt514-mt523 (CA)n repeat variations between NAFLD patients and the control group (P < 0.001). C to T and T to C transitions were the prevalent substitution among patients. Identification of the 16220-16221ins C mutation in both blood and tissue samples from NAFLD patients holds substantial promise as a potential diagnostic marker. However, further research is imperative to corroborate these findings.

Total flavonoids of Broussonetia papyrifera alleviate non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signaling pathways

BackgroundsNon-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. The leaves of Broussonetia papyrifera contain a large number of flavonoids, which have a variety of biological functions. MethodsIn vitro experiments, free fatty acids were used to stimulate HepG2 cells. NAFLD model was established in vivo in mice fed with high fat diet (HFD) or intraperitoneally injected with Tyloxapol (Ty). At the same time, Total flavonoids of Broussonetia papyrifera (TFBP) was used to interfere with HepG2 cells or mice. ResultsThe results showed that TFBP significantly decreased the lipid accumulation induced by oil acid (OA) with palmitic acid (PA) in HepG2 cells. TFBP decreased the total cholesterol (TC), the triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDLC) in serum. TFBP could also effectively inhibit the generation of reactive oxygen species (ROS) and restrained the level of myeloperoxidase (MPO), and enhance the activity of superoxide dismutase (SOD) to alleviate the injury from oxidative stress in the liver. Additionally, TFBP activated nuclear factor erythroid-2-related factor 2 (Nrf2) pathway to increasing the phosphorylation of AMP-activated protein kinase (AMPK). Meanwhile, protein levels of mTORC signaling pathway were evidently restrained with the treatment of TFBP. ConclusionOur experiments proved that TFBP has the therapeutic effect in NAFLD, and the activation of Nrf2 and AMPK signaling pathways should make sense.

Effects ofsemaglutide-loaded lipid nanocapsules on metabolic dysfunction-associated steatotic liverdisease.

Metabolic dysfunction-associated steatotic liver disease(MASLD) is a highly prevalent chronic liver disease that can progress to end-stage conditions with life-threatening complications, but no pharmacologic therapy has been approved. Drug delivery systems such as lipid nanocapsules (LNC) are very versatile platforms that areeasy to produce and can induce the secretion of the native glucagon-like peptide 1 (GLP-1) when orally administered. GLP-1 analogs are currently being studied in clinical trials in the context of MASLD. Our nanosystem provides with increased levels of the native GLP-1 and increased plasmatic absorption of the encapsulated GLP-1 analog (semaglutide). Our goal was touse our strategy to demonstrate a better outcome and a greater impact on the metabolic syndrome associated with MASLD and on liver disease progression with our strategy compared with the oral marketed version of semaglutide, Rybelsus®. Therefore, we studied the effect of our nanocarriers on a dietary mouse model of MASLD, the Western diet model, during a daily chronic treatment of 4weeks. Overall, the results showed a positive impact of semaglutide-loaded lipid nanocapsules towards the normalization of glucose homeostasis and insulin resistance. In the liver, there were no significant changes in lipid accumulation, but an improvement in markers related to inflammation was observed. Overall, our strategy had a positive trend on the metabolic syndrome and atreducing inflammation, mitigating the progression of the disease. Oral administration of the nanosystem was more efficient at preventing the progression of the disease to more severe states when compared to the administration ofRybelsus®, as a suspension.

Non-alcoholic Fatty Liver Disease Among Iraqi Patients With Psoriasis: A Case-Control Study.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Several studies have shown that patients with psoriasis have a higher risk of developing NAFLD. Obesity, metabolic syndrome, and cytokine-mediated inflammation might be the link between psoriasis and NAFLD. This study aims to investigate the prevalence of NAFLD among psoriatic Iraqi patients and examine the relationship with disease severity using the Psoriasis Area and Severity Index (PASI) score and the correlation with different clinical and laboratory parameters. A case-control study on 130 psoriatic patients and 130 age-, sex-, and BMI-matched healthy controls was conducted at the Department of Dermatology in Basra Teaching Hospital from November 2022 to October 2023. All demographic and clinical data were collected using a pre-designed questionnaire, and NAFLD was diagnosed through a FibroScan examination performed on each participant. The severity of psoriasis was determined using the PASI score. Fasting glucose, liver enzymes, and lipid profile levels were investigated, and metabolic syndrome was identified. The prevalence of NAFLD was significantly higher in our psoriatic patients than in the control group (66.2% vs. 42.3%, OR=2.6, P<0.01). Psoriatic patients were found to have more severe NAFLD than the controls, as evidenced by their steatosis and fibrosis staging (P<0.01). In patients with psoriasis, NAFLD was associated with a higher prevalence of diabetes (17.4%) and metabolic syndrome (55.8%). Furthermore, psoriatic patients with NAFLD had significantly higher values of BMI, waist circumference, PASI score, as well as serum alanine transaminase (ALT), triglyceride, cholesterol, low-density lipoprotein (LDL), and fasting glucose levels.The study also found a significant positive correlation between the psoriasis severity based on PASI and the steatosis score. Metabolic syndrome, PASI, BMI, serum triglycerides, LDL, and age are the independent predictors of NAFLD. NAFLD is highly prevalent among psoriatic patients affecting more than half of them and closely associated with metabolic syndrome and severity of psoriasis. Routine screening for NAFLD may be necessary in psoriatic patients particularly when considering the use of hepatotoxic drug therapy.

Assessment of transient elastography in diagnosing MAFLD and the early effects of sleeve gastrectomy on MAFLD among the Chinese population.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease among patients with obesity. Bariatric surgery, such as sleeve gastrectomy (SG), shows promise in improving the unfavorable condition of MAFLD. Transient elastography (TE) can be utilized to assess the extent of steatosis and liver fibrosis, providing a noninvasive method for preoperative prediction and postoperative evaluation of MAFLD. This study aims to investigate the effectiveness of TE in diagnosing MAFLD by evaluating liver steatosis and tissue stiffness, as well as assessing the early impact of SG in the treatment of obesity-associated MAFLD. In this study, the authors collected preoperative and 6-month postoperative data from patients with obesity who were diagnosed with MAFLD by intraoperative liver biopsy. The patients underwent SG at our hospital between August 2021 and April 2023. The authors estimated the diagnostic accuracy for the steatosis and fibrosis categories using the area under the receiver operating characteristic curve (AUROC). The authors also evaluated the influence of disease prevalence on the positive predictive value and negative predictive value. MAFLD diagnosis was based on the liver steatosis activity and fibrosis scoring system. The authors used univariate and multivariate logistic regression analyses to identify factors contributing to severe MAFLD. To visualize the results, the authors created a nomogram and enhanced it with bootstrap resampling for internal validation. Additionally, the authors plotted receiver operating characteristic and calibration curves. The authors compared preoperative and postoperative data, including general information, laboratory tests, and TE results, to assess the early impact of SG in the treatment of obesity-associated MAFLD. Based on the results of liver biopsy, the AUROC for controlled attenuation parameter (CAP) in identifying steatosis was found to be 0.843 (95% CI: 0.729-0.957) for S≥S1, 0.863 (95% CI: 0.786-0.940) for S≥S2, and 0.872 (95% CI: 0.810-0.934) for S=S3. The Youden limits for S≥S1, S≥S2, and S≥S3 were determined to be 271 dB/m, 292 dB/m, and 301 dB/m, respectively. Similarly, the AUROC for liver stiffness measurement (LSM)/E in detecting liver fibrosis was 0.927 (95% CI: 0.869-0.984) for F≥F2, 0.919 (95% CI: 0.824-0.979) for F≥F3, and 0.949 (95% CI: 0.861-0.982) for F=F4, with Youden cutoff values of 7.5kPa, 8.3kPa, and 10.4kPa, respectively. Patients with A≥3 and/or F≥3 were classified as having severe MAFLD. Multivariate logistic regression analysis identified CAP, E, LDL, and AST as the best diagnostic factors for severe MAFLD, and a nomogram was constructed based on these factors. The AUROC of the nomogram for the assessment of severe MAFLD was 0.824 (95% CI: 0.761-0.887), which was further validated by 1000 bootstrap resamplings with a bootstrap model area under curve of 0.823. Finally, after a 6-month follow-up period, the steatosis grade and fibrosis stage of the patients were graded based on the optimal cutoff values for CAP and LSM. Significant reductions in BMI, waist circumference, HbA1c, fasting glycemia, triglycerides, high density lipoprotein (HDL), glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), gamma glutamyl transpeptidase (GGT), CAP, LSM, steatosis grade, and fibrosis stage were observed compared to the preoperative values. In this prospective study, the authors investigated the use of CAP and LSM as alternatives to liver biopsy for evaluating hepatic steatosis and fibrosis in patients with obesity combined with MAFLD. Furthermore, the authors examined the impact of SG on metabolic indicators and the progression of fatty liver disease during the early postoperative period, and observed significant improvements in both aspects.

Clinical Management practice and Therapeutic Outcomes of Chronic Liver Disease patients in the Conflicted area of North Ethiopia

Background: In the 21st century, low- and middle income, war prone and drought-prone areas in developing nations have seen a fast rise in the prevalence of chronic liver disease (CLD). An estimated 240 million people worldwide are infected with HIV, and 780,000 deaths are attributed to it each year, according to the World Health Organization (WHO). Objective: We want to assess the efficacy of in-hospital care for CLD patients by verifying and evaluating current management practices. Method: A retrospective descriptive study of patients with chronic liver disease who were followed up on at Debre Berhan Hospital between July 2018 and January 2021 was conducted. Results: Out of a total of 209 patients tested, 127 (or 60.74%) were males aged 41.44±12.89 of years. Ascites complications were presented in over 44% of cases. Using the laboratory data, 65 patients (31.10%) and 71 patients (33.97%) were found to have abnormally high AST and ALT values on LFTs testing. AUROC analysis was carried out with a 95% CI for Child-Pugh of 0.61 (0.53-0.75, P=0.14), MELD 0.75 (0.63-0.72, P=0.26), and ALBI 0.53 (0.31-0.54, P=0.29). Conclusion: Based on the predictive data, 87 (41.63%) patients were successfully treated and released, whereas 57(27.27%) were recommended for further care, and 47 died due to co-morbid conditions. Although, the study period coincides with the COVID-19 pandemic, more analysis of the obtained data is necessary.

Investigation of the Association between Air Pollution and Non-Alcoholic Fatty Liver Disease in the European Population: A Mendelian Randomization Study.

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease worldwide. At the same time, the relationship between air pollution and the likelihood of developing NAFLD has been a subject of debate due to conflicting findings in previous observational research. Our objective was to examine the potential correlation between air pollutant levels and the risk of NAFLD in the European population by employing a two-sample Mendelian randomization (MR) analysis. The UK Biobank Consortium provided the summary statistics for various air pollution indicators (PM2.5, PM2.5 absorbance, PM2.5-10, PM10, NO2, and NOx). Additionally, information on NAFLD was obtained from three studies, including one derivation set and two validation sets. Heterogeneity, pleiotropy, and sensitivity analyses were performed under different MR frameworks, and instrumental variables associated with confounders (such as education, smoking, alcohol, and BMI) were detected by tools. In the derivation set, causal relationships between PM2.5, NO2, and NAFLD were observed in univariable Mendelian randomization (UVMR) (Odds Ratio (OR) = 1.99, 95% confidence interval (95% CI) = [1.22-3.22], p = 0.005; OR = 2.08, 95% CI = [1.27-3.40], p = 0.004, respectively). After adjustment for air pollutants or alcohol intake frequency in multivariable Mendelian randomization (MVMR), the above genetic correlations disappeared. In validation sets, the null associations remained in UVMR. Our findings from MR analysis using genetic data did not provide evidence for a causal association between air pollution and NAFLD in the European population. The associations observed in epidemiological studies could be partly attributed to confounders.

Curcumin is a potential therapeutic agent that ameliorates diabetes among non-alcoholic fatty liver disease coexist with type 2 diabetes

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) harmonize and act synergistically in clinical practices. About 70–80% of diabetic patients develop NAFLD. At the same time, NAFLD existence increases T2DM development. Meanwhile, the presence of T2DM increases the progression to liver disease such as NAFLD, and to non-alcoholic steatohepatitis (NASH). The most prevalent chronic liver disease worldwide is a NAFLD. NAFLD and (T2DM) have a two-way pathophysiologic relationship, with the latter driving the development of the former into NASH. Nonetheless, NASH enhances the threat of cirrhosis as well as hepatocellular carcinoma (HCC), both cases in turn need transplantation of the liver. The only treatment for NAFLD is still lifestyle management because there are no FDA-approved drugs for the condition. In the current study, we review how curcumin (a naturally occurring phytopolyphenol pigment) treats NAFLD. Also we showed broad insights on curcumin-based therapy, by severe reduction of hepatic inflammation. Thus, our review showed that curcumin ingestion considerably decreased glycemic parameters (fasting blood glucose, glycosylated hemoglobin, insulin resistance index (HOMA-IR), and free fatty acids) and adipocyte-fatty acid binding protein (A-FABP), and adipokine released from adipocytes. Clinical trials are needed to evaluate the effects of curcumin and its specific dosage on liver enzymes, glycemic consequences, among NAFLD coexist with T2DM patients.

Transcriptomics-driven metabolic pathway analysis reveals similar alterations in lipid metabolism in mouse MASH model and human

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease worldwide, and can rapidly progress to metabolic dysfunction-associated steatohepatitis (MASH). Accurate preclinical models and methodologies are needed to understand underlying metabolic mechanisms and develop treatment strategies. Through meta-analysis of currently proposed mouse models, we hypothesized that a diet- and chemical-induced MASH model closely resembles the observed lipid metabolism alterations in humans.MethodsWe developed transcriptomics-driven metabolic pathway analysis (TDMPA), a method to aid in the evaluation of metabolic resemblance. TDMPA uses genome-scale metabolic models to calculate enzymatic reaction perturbations from gene expression data. We performed TDMPA to score and compare metabolic pathway alterations in MASH mouse models to human MASH signatures. We used an already-established WD+CCl4-induced MASH model and performed functional assays and lipidomics to confirm TDMPA findings.ResultsBoth human MASH and mouse models exhibit numerous altered metabolic pathways, including triglyceride biosynthesis, fatty acid beta-oxidation, bile acid biosynthesis, cholesterol metabolism, and oxidative phosphorylation. We confirm a significant reduction in mitochondrial functions and bioenergetics, as well as in acylcarnitines for the mouse model. We identify a wide range of lipid species within the most perturbed pathways predicted by TDMPA. Triglycerides, phospholipids, and bile acids are increased significantly in mouse MASH liver, confirming our initial observations.ConclusionsWe introduce TDMPA, a methodology for evaluating metabolic pathway alterations in metabolic disorders. By comparing metabolic signatures that typify human MASH, we show a good metabolic resemblance of the WD+CCl4 mouse model. Our presented approach provides a valuable tool for defining metabolic space to aid experimental design for assessing metabolism.

Global status and trends in hepatitis B virus DNA mutation research from 2003 to 2022: A comprehensive bibliometric view

AbstractAimsHepatitis B virus (HBV) is an enveloped DNA virus belonging to the Hepadnaviridae family. It is a significant contributor to the prevalence of chronic liver disease on a global scale. Mutations in HBV DNA can affect the diagnosis, treatment, and prognosis of patients with chronic hepatitis B. Although numerous studies on HBV DNA mutations have been conducted, few bibliometric studies have been performed to date. This study aimed to analyze changes in scientific output to gain a better understanding of the current research status and identify potential new research directions in the field of HBV DNA mutation.MethodsRelevant studies published between 2003 and 2022 were retrieved from the Web of Science Core Collection database. CiteSpace version 6.1.R6 was used to construct network maps to evaluate collaborations among countries, institutions, authors, journals, and keywords.ResultsIn total, 1508 publications over the past 20 years were obtained, mainly from China, the United States, and Japan. The major research institutions in China included the University of Hong Kong, Fudan University, and Peking University. Lai Ching Lung was the most productive author, whereas Anna Suk‐Fong Lok was the most frequently co‐cited author. The keyword “HBsAg” was the strongest burst keyword in recent years, indicating possible future study trends.ConclusionsThis bibliometric analysis intuitively revealed the overall research status of HBV DNA mutations, providing valuable information for researchers, funding agencies, and policymakers to explore the current research status, research hotspots, and new directions for future research.

The beneficial hepatic effects of glucagon‐like peptide 1 receptor agonists in patients with diabetes and metabolic dysfunction‐associated steatotic liver disease are independent of weight loss

AbstractBackgroundMetabolic dysfunction‐associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. Despite resmetirom being recently approved for treatingnon‐cirrhotic MASH patients in the United States of America (but not elsewhere), weight loss and lifestyle remain the first line and mainstay for treating the condition. Glucagon‐like peptide 1 receptor agonists (GLP‐1RAs) have shown promise in MASLD treatment, as they promote significant weight loss.AimsIn this study, we assessed the effect of long‐term GLP‐1 therapy on liver disease severity in a cohort of patients with Type 2 diabetes and MASLD.Materials and methodsIn this retrospective observational study, we included all new MASLD patients seen in the liver clinic (Imperial College Healthcare NHS Trust) from January 2010 to May 2022. Demographic, anthropometric and clinical data were collected at baseline and at the most recent follow‐up.Results779 patients were included. Among those with Type 2 diabetes mellitus (T2DM) (n = 335), 94 (28%) were prescribed a GLP‐1RA for a median period of 38 (1–171.2) months. In those on GLP‐1RA, there was a significant improvement in BMI (33.1 vs. 34.9 kg/m2, p = 0.005), alanine aminotransferase (ALT) (37 vs. 58 IU/L, p = 0.009), HbA1c (58 vs. 61 mmol/lL, p = 0.006) and CAP score (331 vs. 354 dB/m, p = 0.0001) at the end of follow‐up. Finally, among those who were treated with GLP‐1RA, 37 patients had &lt;5% weight loss over a median of 38 (10–134) months. In this group, there was also a significant reduction in ALT (32 vs. 58 IU/L, p = 0.0001), AST (30 vs. 36 IU/L, p = 0.004) and CAP score (329 vs. 349 dB/m, p = 0.05) compared with those who lost &gt;5% weight. In this real‐life cohort of patients with diabetes and MASLD, treatment with GLP‐1RA was associated with greater weight loss and hepatic fat reduction. Of note, a reduction in fat content was observed also in those who did not lose weight.ConclusionTreatment with GLP‐1RA should be favoured when treating patients with co‐existing diabetes and MASLD.