Prevalence Of Liver Disease Research Articles

Type 2 Diabetes Mellitus in Inflammatory Bowel Disease Patients: A Case-Control Study Through a Long Follow-Up Period.

Background/Objectives: The characterization of patients with inflammatory bowel disease (IBD) and type 2 diabetes mellitus (T2DM) as a new group has not been well detailed. This study aimed to evaluate the impact of T2DM on IBD progression and analyze the prevalence of steatotic liver disease and liver damage in these patients. Methods: Through a retrospective case-control study, we compared severe IBD occurrence in patients with both IBD-T2DM (cases) versus those with IBD alone (controls). Among 1047 medical records, 79 IBD-T2DM patients were selected and compared to 308 controls in a 1:4 ratio. Severe IBD was defined by variables such as surgery, target therapy, corticosteroid use, and hospitalization. Liver damage was assessed using Fib-4 (>1.3), and hepatic steatosis was evaluated by imaging. Results: There was no significant difference in severe disease rates (59.5% vs. 59.7%; p = 0.97). IBD-T2DM patients had higher rates of hepatic steatosis (62.9% vs. 27.2%; p < 0.0001) and liver damage (55.4% vs. 26.6%; p < 0.0001). IBD-T2DM patients used more corticosteroids (p < 0.0001) and fewer anti-TNF-alpha drugs (p = 0.007). The median age at diagnosis was higher in IBD-T2DM patients (48 vs. 32; p < 0.0001). In Crohn's disease, 24.3% of IBD-T2DM patients had exclusive colonic involvement compared to 5% in the IBD-only group (p = 0.003). Conclusions: T2DM was not associated with worse IBD progression, but was linked to increased liver steatosis and damage. Differences such as age of onset, colonic involvement, and liver damage suggest that IBD-T2DM patients could configure a special population worthy of further studies.

Prevalence of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) in Persons with Obesity and Type 2 Diabetes Mellitus: A Cross-sectional Study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important entity in patients with type-2 diabetes (T2D). Exploring the prevalence and related factors of MASLD is vital toward developing effective methods of diagnosis and treatment. The objective of this study was to determine the prevalence of MASLD in persons with obesity and T2D. This cross-sectional study was conducted at a private healthcare facility (Medicell Clinics) in Karachi, Pakistan, reviewing records from January to December 2022. Persons of either gender aged 18 or above with a diagnosis of T2D and/or obesity were analyzed. Of a total of 646 persons, 430 (66.6%) were females. The mean age was 48.58 ± 13.88 years, ranging between 18 and 85 years. T2D was noted in 351 (54.3%) patients, while obesity was observed in 593 (91.8%) persons, 396 (61.3%) had MASLD. Persons having MASLD had significantly higher body mass index (31.16 ± 5.13 vs 28.14 ± 4.76 kg/m2, p < 0.001). Likewise, obesity was significantly associated with MASLD (94.9 vs 86.8%, p < 0.001). The odds ratios (OR) and 95% confidence intervals (CIs) are reported in multivariate logistic regression table. Persons with T2DM (OR = 1.519, p = 0.009), and obesity (OR = 2.651, p = 0.001) showed significantly increased odds of having MASLD. The analysis revealed that individuals in the age-group of 18-40 (OR = 1.627, p = 0.014) had increased odds of having MASLD. The prevalence of MASLD was very high in persons with T2D, and obesity. Type-2 diabetes with or without obesity, or the other way around, significantly increases the risk of MASLD. Therefore, these persons should be screened for MASLD to improve clinical outcomes in the affected people. Latif S, Ahsan T. Prevalence of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) in Persons with Obesity and Type 2 Diabetes Mellitus: A Cross-sectional Study. Euroasian J Hepato-Gastroenterol 2024;14(2):129-133.

Inhibition of intracellular versus extracellular cathepsin D differentially alters the liver lipidome of mice with metabolic dysfunction-associated steatohepatitis.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) progressing to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatic inflammation, has significantly increased in recent years due to unhealthy dietary practices and sedentary lifestyles. Cathepsin D (CTSD), a lysosomal protease involved in lipid homeostasis, is linked to abnormal lipid metabolism and inflammation in MASH. Although primarily intracellular, CTSD can be secreted extracellularly. Our previous proteomics research has shown that inhibition of extracellular CTSD results in more anti-inflammatory effects and fewer potential side effects compared to intracellular CTSD inhibition. However, the correlation between reduced side effects and alterations in the hepatic lipid composition remains unknown. This study aims to investigate the correlation between intra- and extracellular CTSD inhibition and potential alterations in the hepatic lipid composition in MASH. Low-density lipoprotein receptor knockout (Ldlr-/-) mice were fed a high-fat diet for 10 weeks and received subcutaneous injections every 2 days of vehicle, intracellular CTSD inhibitor (GA-12), or extracellular CTSD inhibitor (CTD-002). Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize and compare the lipid composition in liver tissues. Hepatic phosphatidylcholine remodeling was observed with both inhibitors, suggesting their therapeutic potential in treating MASH. Treatment with an intracellular CTSD inhibitor resulted in elevated levels of cardiolipin, reactive oxygen species, phosphatidylinositol, phosphatidylethanolamine, and lipids that are linked to mitochondrial dysfunction and inflammation, and induced more oxidative stress. The observed modifications in lipid composition demonstrate the clinical advantages of extracellular CTSD inhibition as a potentially beneficial therapeutic approach for MASH.

Identification of hub biomarkers in liver post-metabolic and bariatric surgery using comprehensive machine learning (experimental studies).

The global prevalence of non-alcoholic fatty liver disease (NAFLD) is approximately 30%, and the condition can progress to non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Metabolic and bariatric surgery (MBS) has been shown to be effective in treating obesity and related disorders, including NAFLD. In this study, comprehensive machine learning was used to identify biomarkers for precise treatment of NAFLD from the perspective of MBS. Differential expression and univariate logistic regression analyses were performed on lipid metabolism-related genes in a training dataset (GSE83452) and two validation datasets (GSE106737 and GSE48452) to identify consensus predicted genes (CPGs). Subsequently, 13 machine learning algorithms were integrated into 99 combinations; among which, the optimal combination was selected based on the total score of the area under the curve, accuracy, F-score, and recall in the two validation datasets. Hub genes were selected based on their importance ranking in the algorithms and the frequency of their occurrence. Finally, a mouse model of MBS was established and the mRNA expression of the hub genes was validated via quantitative PCR. A total of 12 CPGs were identified after intersecting the results of differential expression and logistic regression analyses on a Venn diagram. Four machine learning algorithms with the highest total scores were identified as optimal models. Additionally, PPARA, PLIN2, MED13, INSIG1, CPT1A, and ALOX5AP were identified as hub genes. The mRNA expression patterns of these genes in mice subjected to MBS were consistent with those observed in the three datasets. Altogether, the six hub genes identified in this study are important for the treatment of NAFLD via MBS and hold substantial promise in guiding personalized treatment of NAFLD in clinical settings.

Non-Invasive Tests of Non-Alcoholic Fatty Liver Disease: Perspective Review

Cirrhosis and hepatocellular carcinoma often develop from Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive condition characterized by hepatic steatosis, inflammation and varying degrees of fibrosis. The increasing incidence of non-alcoholic steatohepatitis (NASH) highlights the need for effective diagnostic and treatment methods. Non-invasive tests (NITs) have emerged as promising tools for evaluating and monitoring NAFLD, offering safer and more cost-effective alternatives to invasive liver biopsies. This review focuses on the current state of NITs in NAFLD management, emphasizing their diagnostic accuracy, prognostic significance, and role in guiding treatment. NITs discussed include transient elastography, magnetic resonance imaging (MRI), magnetic resonance elastography (MRE) and serum biomarker panels such as the NAFLD fibrosis score, Fibro Test, and Enhanced Liver Fibrosis (ELF) test. Recent advancements in MRI and MRE have greatly improved the non-invasive assessment of liver fibrosis and steatosis, enhancing sensitivity and specificity for early detection and risk stratification. Additionally, combined serum biomarker panels have shown promise in predicting disease severity and progression, aiding in the identification of high-risk patients who could benefit from early intervention. By enabling prompt diagnosis, comprehensive risk assessment and monitoring of disease progression, the integration of NITs into standard clinical practice offers significant potential for improving NAFLD management. Ongoing research efforts are focused on developing new NITs and optimizing existing methods to enhance diagnostic precision and prognostic evaluation in NAFLD patients. This evolving landscape of non-invasive assessment tools could revolutionize the approach to managing this increasingly prevalent liver disease. Keywords: Fatty liver, Liver biopsy, Transient Elastography, Serum biomarkers, Hepatic Cell Carcinoma.

Prevalence of metabolic dysfunction-associated steatotic liver disease and fibrosis defined by liver elastography in the United States using National Health and Nutrition Examination Survey 2017-March 2020 and August 2021-August 2023 data.

Steatotic liver disease (SLD) is a significant public health burden. Previously, we estimated prepandemic SLD prevalence determined by transient elastography-assessed hepatic steatosis and fibrosis in the United States. We now estimate the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and examine associations with lifestyle, socioeconomic, and other factors. Liver stiffness and controlled attenuation parameters were assessed on 13,538 non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic men and women aged 20 years and over in the National Health and Nutrition Examination Survey 2017 to March 2020 and August 2021 to August 2023. The prevalence of SLD (controlled attenuation parameter >300dB/m) was 28.7%, fibrosis (liver stiffness >8kPa) was 11.3%, and MASLD was 25.6%. Between the 2 survey cycles, the age-standardized SLD prevalence was not significantly different, MASLD prevalence decreased (26.8%-23.6%), and fibrosis prevalence increased (10.4%-12.7%). In multivariable-adjusted analysis, both MASLD and fibrosis were associated with diabetes, higher body mass index, higher waist-to-hip ratio, elevated blood pressure, and inversely associated with non-Hispanic Black race-ethnicity. MASLD was also associated with male sex, non-Hispanic Asian race-ethnicity, prediabetes, higher total cholesterol, lower HDL cholesterol, and greater sedentary lifestyle. Fibrosis was also associated with SLD, lower total cholesterol, and less education. In the US population, MASLD and fibrosis prevalence are high along with obesity and diabetes. Our findings suggest that early detection of chronic liver disease and targeting lifestyle and other modifiable risk factors may slow disease progression toward advanced fibrosis and cirrhosis.

IL-6-Mediated Liver Regeneration: Exploring Key Signaling Pathways and Cellular Mechanisms

The liver is a vital organ responsible for a variety of essential functions in the human body, and the growing prevalence of liver damage and disease highlights the need to understand the liver's inherent regenerative capacity. Research into liver regeneration has shown that, among the numerous cytokines involved, interleukin-6 (IL-6) plays a critical and irreplaceable role. Without IL-6, the liver cannot effectively regenerate, underscoring its significance. This review examines IL-6 in detail, including its interaction with its receptor and its involvement in three distinct signaling modes: classical, trans-signaling, and cluster signaling. Additionally, it explores two key pathways activated by IL-6 that drive liver regeneration: the JAK/STAT and Ras/MAPK pathways, both of which are crucial for promoting hepatocyte proliferation and tissue repair. Understanding the precise mechanisms through which IL-6 regulates these signaling pathways, as well as its role in liver regeneration under varying degrees of injury, offers valuable insights that have broad implications for treating liver diseases and improving human health.

Investigation of Active Components of Meconopsis integrifolia (Maxim.) Franch in Mitigating Non-Alcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) has rapidly emerged as the most prevalent chronic liver disease globally, representing a significant and escalating public health challenge. Meconopsis integrifolia (Maxim.) Franch, a traditional Tibetan medicinal herb used for treating hepatitis, remains largely unexplored regarding its therapeutic potential and active components in combating NAFLD. This study first evaluated the in vitro lipid accumulation inhibitory activity of different extraction fractions of M. integrifolia using a HepG2 cell steatosis model. The ethyl acetate fraction was found to significantly reduce triglyceride (TG) and low-density lipoprotein (LDL) levels, inhibit lipid droplet deposition in HepG2 cells, and promote lipid metabolism balance through modulation of the AMPK/SREPB-1c/PPAR-α signaling pathway. Further analysis utilizing chromatographic techniques and nuclear magnetic resonance spectroscopy (NMR) led to the isolation of 13 compounds from the active ethyl acetate fraction. Notably, compounds 6, 9, 10, 11, 12, and 13 were identified for the first time from this Tibetan herb. In vitro activity assays and molecular docking analyses further confirmed that the compounds Luteolin (1), Quercetin 3-O-[2‴, 6‴-O-diacetyl-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (6), and Quercetin 3-O-[2‴-O-acetyl-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (8) are potential key components responsible for the NAFLD-ameliorating effects of M. integrifolia. This study highlights the therapeutic potential of M. integrifolia in treating NAFLD and provides a foundation for its further development and application, underscoring its significance in the advanced utilization of traditional Tibetan medicine.

Evaluating the Role of Aspirin in Liver Disease: Efficacy, Safety, Potential Benefits and Risks.

The rise in liver disease incidence and prevalence has led to increasing morbidity and mortality worldwide. Persistent hepatic inflammation drives disease progression by increasing fibrosis, advancing to cirrhosis, and potentially developing into hepatocellular carcinoma (HCC). Addressing these complications is essential to reduce liver-related mortality. Recent studies suggest that non-steroidal anti-inflammatory drugs, particularly aspirin, may play a beneficial role in managing liver disease. Aspirin's anti-inflammatory and chemoprotective effects contribute to slowing disease progression and reducing the risks associated with chronic liver disease (CLD). This review highlights the current literature on the effects of aspirin in CLD, with a focus on patients with metabolic-associated steatotic liver disease (MASLD) and hepatitis B and C. We will examine aspirin's potential ability to mitigate fibrosis, reduce the incidence of HCC, and lower liver-related mortality. Additionally, we will discuss its potential side effects and safety considerations, particularly in the context of liver disease, where there is an increased risk of bleeding.

Therapeutic potential of the flavonoid compound Licochalcone D in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease associated with type 2 diabetes, which doubles the risk of developing this condition. Various flavonoid compounds have a positive effect on lipid metabolism, inflammation, and insulin resistance and can contribute to slowing down the progression of MASLD. In the current study, we investigated the biological effects of Licochalcone D (Lico D), a flavonoid, in a metabolic disease model. Oil Red O staining, quantitative real-time polymerase chain reaction, and western blotting were performed. For in vivo experiments, we used high-fat diet (60%) plus low-dose streptozotocin (30mg/kg; 5 days; intraperitoneal)-induced metabolic disease mouse model and evaluated lipid metabolism. We observed that Lico D reduced lipid accumulation and increased lipid metabolism both in vitro and in vivo. Additionally, we identified that the AMP-activated protein kinase and Sirtuin 1 pathways were activated in the mouse liver and hepatic steatosis cell model. In silico analysis revealed that Lico D passes the "Lipinski Rule of Five," which indicates drug-likeness properties. In conclusion, our findings highlight the role of Lico D in improving metabolic dysfunction-associated steatotic liver disease.

Adult-based genetic risk scores for insulin resistance associate with cardiometabolic traits in children and adolescents.

Insulin resistance (IR) is a key factor in the development of cardiometabolic diseases. While genetic risk scores (GRSs) for IR have been developed and validated in adult population, it is unclear if they can be used for risk assessment in youth. Our objective was to investigate whether adult-derived genetic risk scores (GRSs) for insulin resistance (IR) associate with cardiometabolic traits in children and adolescents. We studied a group of children and adolescents with obesity (n= 1,680) and a group without obesity (n=1,804). We constructed three GRSs based on fasting (IR-GRS27), oral glucose tolerance test (IR-GRS8), and IR-related phenotypes (IR-GRS51) from previous genome-wide association studies. Using an additive genetic model, we calculated weighted GRSs and analysed their associations with cardiometabolic traits using linear and logistic regression models. The IR-GRS27 was associated with higher serum concentrations of fasting insulin, C-peptide, triglyceride (TG), gamma-glutamyl transferase and alanine aminotransferase (ALT), and homeostatic model assessment of insulin resistance. The IR-GRS27 was furthermore associated with higher prevalence of IR and ALT. IR-GRS51 was associated with higher TG and lower high-density lipoprotein cholesterol, while IR-GRS8 associated with lower total cholesterol, low-density lipoprotein cholesterol, and increased ALT. IR-GRS27 and IR-GRS8 were additionally associated with higher prevalence of IR and steatotic liver disease respectively. Adult-derived GRSs for IR are significantly associated with cardiometabolic traits in children and adolescents. If validated in independent study samples, our findings suggest the contribution of adult-based GRSs in assessing IR-related cardiometabolic risk in youth.

Fanlian Huazhuo Formula: A promising herbal preparation for metabolic liver disease.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased significantly in recent decades and is projected to increase further due to the rising obesity rates. MASLD patients are at higher risk of developing advanced liver diseases "cirrhosis and hepatocellular carcinoma" as well as liver- or cardiovascular-related mortality. Existing lipid-lowering therapies failed to reduce the risk of mortality in these patients. Therefore, there is an urgent need for pharmacotherapies that can control and even reverse this disease. Fanlian Huazhuo Formula (FLHZF) is a combination herbal preparation, and its various individual constituents regulate hepatic lipid metabolism, adipose tissue inflammation, and gut microbiota. Despite, these useful effects, limited information is available on its benefits in diet-induced hepatosteatosis. In this article, we discuss the research findings recently published about the therapeutic effects of FLHZF in suppressing MASLD development and underlying mechanisms. Utilizing a series of in vitro and in vivo experiments, the authors demonstrated for the first time that FLHZF suppresses MASLD in male mice possibly by inhibiting hepatic de novo lipogenesis pathways and reducing hepatocyte death. This study paves the way for future investigations aimed at investigating FLHZF's role in inhibiting lipogenesis particularly using radioactively-labeled glucose and acetate, and governing hepatocyte mitochondrial function, gut microbiome profile, and its effects in other models of MASLD, and female mice.

Effect of bariatric endoscopy on liver fibrosis and steatosis and the course of NAFLD - a prospective interventional study.

With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. NCT04895943.

Cardiometabolic risk factors and clinical course of liver cirrhosis.

The global prevalence of Metabolic Dysfunction-Associated Liver Disease is dramatically increasing with the diffusion of cardiometabolic risk factors (CMRFs). The aim of the present study was to assess the natural course of liver cirrhosis, in terms of decompensation, development of hepatocellular carcinoma and mortality, in relation to the presence of CMRFs (type 2 diabetes mellitus, obesity, arterial hypertension, low HDL levels, hypertriglyceridemia). 667 patients with liver cirrhosis (50 with CMRFs and without non-metabolic aetiological factors, 167 with non-metabolic aetiological factors and without CMRFs, and 450 with both non-metabolic aetiological factors and at least one CMRF) followed at the University and General Hospital of Padua, Italy, from 1998 to 2022, were included. No difference in the occurrence of cirrhosis decompensating events and development of hepatocellular carcinoma was observed, whereas patients in the metabolic or mixed group had 4-3-fold higher all-cause mortality and significantly lower 3-years survival compared to patients in the non-metabolic group, despite a better liver function at enrolment. Hypertriglyceridemia and low HDL levels were the less prevalent CMRFs, but those associated with the highest risk of cirrhosis decompensation. Hypertriglyceridemia was also associated with an increased risk of mortality. Arterial hypertension was associated with a reduced risk of cirrhosis decompensation, but a higher risk of mortality. Compared to patients without CMRFs, those with CMRFs had similar rates of liver cirrhosis decompensation but higher overall mortality. Hypertriglyceridemia was associated with a high risk of both liver decompensation and death.

P67 Prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease and the diagnostic accuracy of non-invasive biomarkers for liver fibrosis in patients with psoriasis

Abstract Psoriasis has been associated with an increased risk of liver fibrosis. Recent studies indicate that metabolic dysfunction-associated steatotic liver disease (MASLD) might be the underlying cause. Furthermore, no clear consensus exists on how to monitor patients with psoriasis for liver fibrosis. Therefore, we assessed the prevalence of MASLD and examined the diagnostic accuracy of non-invasive biomarkers for liver fibrosis. We included patients with psoriasis from a prospective observational cohort study at a university hospital. The prevalence of MASLD was assessed using Fibroscan with hepatic steatosis defined as a controlled attenuation parameter of &amp;gt;250 dB/m and significant/advanced fibrosis as a median liver stiffness measurement (LSM) ≥8 kPa. Non-invasive biomarkers for fibrosis included, fibrosis-4 index (FIB-4, increased if ≥1.3), N-terminal propeptide of collagen type III (PIIINP, increased if &amp;gt;11.0 µg/L for ≤40 years and &amp;gt;9.5 µg/L for &amp;gt;40 years), and the enhanced liver fibrosis (ELF) test (increased if ≥9.8). Analyses were parametric or non-parametric depending on the distribution of data. We enrolled 403 patients (median age 53 years, 54% men). The mean body mass index was 27.8 (standard deviation ± 6.0). In the self-reported questionnaire, 5% of the patients reported consuming &amp;gt;16 units of alcohol per week, 31% reported having hypertension, 28% dyslipidaemia, and 6% Type 2 diabetes. Most patients (75%) received systemic treatment (conventional or biologics), while 25% only used topicals. The patients were generally well-treated with a median psoriasis area and severity index (PASI) of 2.6 (range, 0–41). Based on the FibroScan, 40% had hepatic steatosis (mean CAP 245, ±55 dB/m). The proportion with possible fibrosis was 5% based on FibroScan (median LSM, 4.9 kPa; range, 1.8–20.6), 24% based on FIB-4 (median, 0.89; range, 0.19–8.11), 20% based on ELF (mean, 9.0, ±0.98), and 14% based on PIIINP (median, 6.9 µg/L; range, 2.3–23.1). Pearson’s correlation coefficient between liver fibrosis and the non-invasive biomarkers was highest for FIB-4 (r = 0.57), with corresponding values of r = 0.40 for ELF and r = 0.30 for PIIINP. Furthermore, with Fibroscan as the gold standard, FIB-4 and ELF had better diagnostic accuracy than PIIINP for diagnosing liver fibrosis with an area under the receiver operating characteristic curve of 0.92 (95% confidence interval, 0.87–0.97) for FIB-4, 0.90 (0.83–0.97) for ELF, and 0.77 (0.66–0.87) for PIIINP. In conclusion, 40% of the patients had liver steatosis and 5% displayed liver fibrosis as determined by Fibroscan. FIB-4 and ELF tests demonstrated superior diagnostic accuracy compared with PIIINP.

Integrated metabolomics and network pharmacology analysis to reveal the protective effect of Complanatoside A on nonalcoholic fatty liver disease.

The rising prevalence and severe consequences of nonalcoholic fatty liver disease (NAFLD) have driven the quest for preventive medications. Complanatoside A (CA) is the marked flavonoid of Astragali complanati semen, a traditional Chinese herb that acts on the liver meridian and is widely used to treat liver problems. CA has been proven to have considerable lipid-lowering and liver-protective effects in vitro. However, the efficacy of CA in preventing NAFLD has yet to be shown in vivo. First, the effectiveness of CA against NAFLD was assessed using a high-fat diet (HFD) mouse model. Second, the CA protective mechanism against NAFLD was investigated using a combined metabolomics and network pharmacology strategy. Differential metabolites were identified by metabolomics-based analyses, and metabolic pathway analysis was accomplished by MetaboAnalyst. Potential therapeutic targets were obtained through network pharmacology. Finally, key targets were identified via compound-target networks and validated by molecular docking and western blotting. CA prevented NAFLD mainly by reducing liver lipid accumulation in HFD mice. Metabolomics identified 22 potential biomarkers for CA treatment of NAFLD, primarily involving glycerophospholipid and arachidonic acid metabolism. Fifty-one potential targets were determined by network pharmacology. Co-analysis revealed that albumin, peroxisome proliferator-activated receptor-alpha, retinoid X receptor alpha, interleukin-6, and tumor necrosis factor alpha were key targets. This experiment revealed that CA has a preventive effect on NAFLD, primarily by regulating the peroxisome proliferator-activated receptor-alpha/retinoid X receptor alpha pathway. Furthermore, it provides evidence supporting the potential use of CA in the long-term prevention of NAFLD.

Age-Specific Prevalence and Impact of Alcohol-Related Liver Disease: A Cross-Sectional Study"

Age-Specific Prevalence and Impact of Alcohol-Related Liver Disease: A Cross-Sectional Study"

A Survey Assessing Nonalcoholic Fatty Liver Disease Knowledge Among Hepatologists and Non-Hepatologists in China.

A global increase in nonalcoholic fatty liver disease (NAFLD) prevalence has been observed in the last decade. This study assesses knowledge, awareness, and clinical practice gaps of hepatologists and non-hepatologists in NAFLD management across hospitals in China. A web-based quantitative survey was conducted, and participants included hepatologists (gastroenterologists and infectious disease specialists) and non-hepatologists (internal medicine specialists, cardiologists, and pharmacists) from various hospitals across China. In total, 1627 healthcare practitioners (HCPs) responded to the survey. This included 658 hepatologists and 969 non-hepatologists. In comparison to 92.6% hepatologists, only 58.0% of non-hepatologists were aware of NAFLD. A higher proportion of hepatologists (82.8%) performed screening for NAFLD compared to non-hepatologists (56.9%). Majority of the hepatologists (70%) and non-hepatologists (67%) were aware of the four primary recommendations for managing NAFLD. Only 11% of hepatologists did not manage NAFLD patients, mainly because they felt they did not have enough time (66.7%). Of the 36% non-hepatologists who did not manage NAFLD, 78.4% stated that NAFLD is not their specialty, and 38.6% were not familiar with the treatment options. Most hepatologists were aware of and agreed to performing screening for NAFLD compared to non-hepatologists. Both hepatologists and non-hepatologists exhibited similar level of understanding on NAFLD management. However, a small percentage of both hepatologists and non-hepatologists admitted that they did not manage NAFLD patients because they were not familiar with available treatment options. This underscores the importance of further educating HCPs involved in managing NAFLD.

Modeling metabolic-associated steatohepatitis with human pluripotent stem cell-derived liver organoids.

Metabolic-associated steatohepatitis (MASH) is one of the most prevalent liver diseases worldwide, with a global prevalence estimated between 3% and 5%, posing a significant health burden. Human liver organoids (HLOs) have previously been generated to model steatohepatitis, offering a potential cellular disease model for studying MASH. However, the current HLO model lacks detailed molecular characterizations and requires further improvement. HLOs derived from human pluripotent stem cells were treated with oleic acid and TGFβ to mimic the MASH progression. Treated HLOs were then analyzed using both bulk and single-cell RNA sequencing. Functional characterization was performed through staining with BODIPY, TMRM, CellROX, and Collagen I, as well as terminal deoxynucleotidyl transferase dUTP nick end labeling and ELISA assays. In addition, a test using the MASH HLO model to validate the hepatoprotective effects of several herb extracts was also conducted. Both RNA-seq and single-cell RNA sequencing demonstrated a close resemblance of multiple molecular signatures and key intercellular communications in and between hepatocyte-like cells and stellate-like cells in the MASH HLO model, compared to human MASH. Furthermore, functional characterizations revealed progressive features of human MASH in the MASH HLO model, including severe steatosis, oxidative stress, mitochondrial dysfunction, inflammation, and fibrosis. In addition, the Schisandra extracts have been demonstrated to have significant antioxidative, anti-inflammatory, and antifibrotic properties in the context of MASH. This study offers an improved HLO disease model of human MASH, which can be potentially applied to facilitate the understanding of the MASH pathogenesis and the discovery of effective treatments.

Non-alcoholic fatty liver disease and the gut microbiota in adolescents: is there a relationship?

BackgroundDespite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), the pathophysiology is still not fully understood. Recent evidence suggests that the gut microbiota may play a role in the pathophysiology of NAFLD and may also offer new therapeutic options.MethodsThis prospective cross-sectional study included 100 consecutive newly diagnosed obese patients (BMI ≥ 95th percentile), aged 14–18 years with NAFLD (confirmed by ultrasound), persistently elevated levels of alanine aminotransferase (ALT) greater than 60 U/L for 1–6 months, and 100 healthy controls. We evaluated changes in the gut microbiota in NAFLD adolescents compared with healthy controls.ResultsAccording to the multiple logistic regressions, the variables associated with NAFLD were the presence of Clostridium difficile, the presence of Salmonella spp., a greater abundance of Bifidobacterium and Prevotella, and a lower abundance of Lactobacillus.ConclusionChanges in the gut microbiota occur in adolescents with NAFLD compared with healthy individuals, which may be useful for identifying youths who are amenable to gut microbiota-based interventions.Clinical trial numberNot applicable.