Types Of Chronic Liver Disease Research Articles

Wedelolactone attenuates liver fibrosis and hepatic stellate cell activation by suppressing the Hippo pathway.

Liver fibrosis is a commonly observed pathological phenomenon that occurs during the progression of various types of chronic liver diseases. The Hippo pathway is closely associated with the pathogenesis of liver fibrosis. Previous studies have shown that wedelolactone (WED) has a significant anti-hepatic fibrosis effect, whereas the target and mechanism underlying WED remain elusive. In this study, we found that WED significantly alleviated liver fibrosis and injury by inhibiting the expression of YAP and TAZ. In an in vitro model, WED suppressed the activation of hepatic stellate cells (HSCs) induced by TGF-β1, as well as the mRNA and protein expression of α-SMA, YAP, and TAZ. The allosteric regulation of YAP by WED was confirmed using MD and CETSA. Moreover, specific knockdown or inhibition of YAP did not enhance the suppressive effect of WED on HSC activation or protein expression associated with fibrosis. These findings demonstrated that the administration of WED effectively alleviated liver fibrosis by suppressing the Hippo/YAP/TAZ pathways. In addition, YAP activity may be regulated by WED via allosteric regulation.

Semaglutide Ameliorates Hepatocyte Steatosis in a Cell Co-Culture System by Downregulating the IRE1α-XBP1-C/EBPα Signaling Pathway in Macrophages.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common type of chronic liver disease. Semaglutide is a glucose-lowering drug administered for the treatment of type 2 diabetes mellitus (T2DM) and is clinically effective in the treatment of NAFLD. X-box binding protein 1 (XBP1) is related to the pathogenesis of both NAFLD and T2DM. The aim of the present study was to demonstrate whether the underlying mechanism of semaglutide treatment for NAFLD is via downregulation of the inositol-requiring transmembrane kinase/endonuclease-1α (IRE1α)-XBP1-CCAAT/enhancer binding protein α (C/EBPα) signaling pathway in macrophages. In the present study, NAFLD cell modeling was induced by oleic acid (0.4 m<sc>m</sc>) and palmitic acid (0.2 m<sc>m</sc>). Hepatocytes (AML12) and macrophages (RAW264.7) were co-cultured in 6-well Transwell plates. Semaglutide (60 or 140 n<sc>m</sc>) was administrated for 24 h, while pioglitazone (2 μ<sc>m</sc>) and toyocamycin (200 n<sc>m</sc>) were used as a positive control drug and a XBP1 inhibitor, respectively. Autophagy and apoptosis of AML12 cells were detected by transmission electron microscopy and Western blotting (WB). Hepatocyte steatosis was evaluated by adopting total intracellular triglyceride determination, analysis of the relative expression of proteins and genes associated with lipid metabolism and hepatocyte Oil red O staining. Detection of inflammation factors was conducted by ELISA and WB. To explore the underlying mechanism of NAFLD treatment with semaglutide, the relative expression of related proteins and genes were tested. Our study demonstrated that semaglutide treatment improved autophagy and inhibited apoptosis of hepatocytes, while notably ameliorating steatosis of hepatocytes. In addition, inflammation was attenuated in the NAFLD cell co-culture model after semaglutide administration. Semaglutide also significantly reduced the protein and gene expression levels of the IRE1α-XBP1-C/EBPα signaling pathway in macrophages. Semaglutide partially ameliorated NAFLD by downregulating the IRE1α-XBP1-C/EBPα signaling pathway in macrophages. These findings may provide a potential theoretical basis for semaglutide therapy for NAFLD.

Quality Improvement: Improving the Screening of Fatty Liver Disease in Patients with Type 2 Diabetes

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common type of chronic liver disease in the world and is projected to become the leading indication for liver transplantation. Studies have shown that in patients with type 2 diabetes mellitus (T2DM), liver steatosis, advanced fibrosis, and cirrhosis were present in 73.8% 15.4%, and 7.7% of patients, respectively. The American Association For The Study Of Liver Disease recently published new guidelines that recommend that all patients with T2DM be screened for MAFLD. The Fibrosis-4 (FIB-4) is a validated non-invasive screening tool that can be used as an initial screen for MAFLD. We identified that T2DM patients were not being screened appropriately in our outpatient internal medicine clinic. The goal of this quality improvement project was to increase the screening of T2DM for NAFLD by creating a smart phrase and providing education to providers. Methods: We reviewed the medical charts for 514 patients with T2DM seen in our Academic Internal Medicine (AIM) Clinic between 2020 and 2022 to assess baseline screening rates. A smartphrase was created through EPIC and included all relevant information to help providers assess for complications of T2DM including MAFLD. For cycle 1, starting in 12/2022, the smart phrase was piloted with 5 residents, and their usage was recorded. For cycle 2, starting 04/2023, the smartphrase was shared with all residents, and multiple educational sessions were held. Usage of the smartphrase, recording a FIB-4 score or collecting labs to do so were monitored. Results: Results of a baseline assessment of 514 patients with T2DM showed that 0 % of patients were screened with a FIB 4 score. During cycle 1, the smart phrase was used in 41% of patient visits when T2DM was addressed. A FIB-4 score was recorded or labs were ordered to do so in 20.9 % of patients. During cycle 2, the smart phrase was used in 10% of patient visits and FIB-4 score was recorded or labs were ordered 10.6% of the time. However, when the smartphrase was used, a FIB-4 score was recorded in 85.7% of the time. Conclusions: It is important to identify individuals with NAFLD while it is in the early stages to prevent progression to cirrhosis and hepatocellular carcinoma. Implementing a smart phrase was shown to improve the screening rates for NAFLD. Further improvement can be made by automatically calculating a FIB-4 score and alerting providers if a FIB-4 score has not been documented in the past 2 years.

UCHL1-dependent control of hypoxia-inducible factor transcriptional activity during liver fibrosis.

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most types of chronic liver disease. At the cellular level, liver fibrosis is associated with the activation of hepatic stellate cells (HSCs) which transdifferentiate into a myofibroblast-like phenotype that is contractile, proliferative and profibrogenic. HSC transdifferentiation induces genome-wide changes in gene expression that enable the cell to adopt its profibrogenic functions. We have previously identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation; however, the cellular targets of its deubiquitinating activity are poorly defined. Here, we describe a role for UCHL1 in regulating the levels and activity of hypoxia-inducible factor 1 (HIF1), an oxygen-sensitive transcription factor, during HSC activation and liver fibrosis. HIF1 is elevated during HSC activation and promotes the expression of profibrotic mediator HIF target genes. Increased HIF1α expression correlated with induction of UCHL1 mRNA and protein with HSC activation. Genetic deletion or chemical inhibition of UCHL1 impaired HIF activity through reduction of HIF1α levels. Furthermore, our mechanistic studies have shown that UCHL1 elevates HIF activity through specific cleavage of degradative ubiquitin chains, elevates levels of pro-fibrotic gene expression and increases proliferation rates. As we also show that UCHL1 inhibition blunts fibrogenesis in a pre-clinical 3D human liver slice model of fibrosis, these results demonstrate how small molecule inhibitors of DUBs can exert therapeutic effects through modulation of HIF transcription factors in liver disease. Furthermore, inhibition of HIF activity using UCHL1 inhibitors may represent a therapeutic opportunity with other HIF-related pathologies.

Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease. However, the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies. Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoetiology and suggest functional therapeutic and diagnostic options. Pyroptosis, ferroptosis, and necroptosis are the main subtypes of non-apoptotic regulated cell deaths (RCDs), each of which represents particular characteristics. Considering the complexity of the findings, the present study aimed to review these types of RCDs and their contribution to NAFLD progression, and subsequently discuss in detail the role of necroptosis in the pathoetiology, diagnosis, and treatment of the disease. The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer, hence it has potential in diagnostic and therapeutic approaches. Nevertheless, further studies are necessary.

Corn Oligopeptide Alleviates Nonalcoholic Fatty Liver Disease by Regulating the Sirtuin Signaling Pathway.

Nonalcoholic fatty liver disease (NAFLD) represents the most prevalent type of chronic liver disease, spanning from simple steatosis to nonalcoholic steatohepatitis (NASH). Corn oligopeptide (CP) is a functional peptide known for its diverse pharmacological effects on metabolism. In this study, we evaluated the protective activity of CP against fatty liver disease. Oral administration of CP significantly reduced body weight gain by 2.95%, serum cholesterol by 22.54%, and liver injury, as evidenced by a reduction of 32.19% in serum aspartate aminotransferase (AST) and 49.10% in alanine aminotransferase (ALT) levels in mice subjected to a high-fat diet (HFD). In a streptozotocin/HFD-induced NASH mouse model, CP attenuated body weight gain by 5.11%, liver injury (with a 34.15% decrease in AST and 11.43% decrease in ALT), and, to some extent, liver inflammation and fibrosis. Proteomic analysis revealed the modulation of oxidative phosphorylation and sirtuin (SIRT) signaling pathways by CP. Remarkably, CP selectively inhibited the hepatic expression of mitochondrial SIRT3 and SIRT5 in both HFD and NASH models. In summary, CP demonstrates a preventive effect against metabolic-stress-induced NAFLD progression by modulating oxidative stress and the SIRT signaling pathway, suggesting the potential of CP as a therapeutic agent for the treatment of NAFLD and advanced-stage NASH.

Identification of key genes and functional enrichment analysis of liver fibrosis in nonalcoholic fatty liver disease through weighted gene co-expression network analysis.

Nonalcoholic fatty liver disease (NAFLD) is a common type of chronic liver disease, with severity levels ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH). The extent of liver fibrosis indicates the severity of NASH and the risk of liver cancer. However, the mechanism underlying NASH development, which is important for early screening and intervention, remains unclear. Weighted gene co-expression network analysis (WGCNA) is a useful method for identifying hub genes and screening specific targets for diseases. In this study, we utilized an mRNA dataset of the liver tissues of patients with NASH and conducted WGCNA for various stages of liver fibrosis. Subsequently, we employed two additional mRNA datasets for validation purposes. Gene set enrichment analysis (GSEA) was conducted to analyze gene function enrichment. Through WGCNA and subsequent analyses, complemented by validation using two additional datasets, we identified five genes (BICC1, C7, EFEMP1, LUM, and STMN2) as hub genes. GSEA analysis indicated that gene sets associated with liver metabolism and cholesterol homeostasis were uniformly downregulated. BICC1, C7, EFEMP1, LUM, and STMN2 were identified as hub genes of NASH, and were all related to liver metabolism, NAFLD, NASH, and related diseases. These hub genes might serve as potential targets for the early screening and treatment of NASH.

Hematological abnormalities in chronic liver disease and their association with severity and types of chronic liver disease

This study aimed to assess the hematological abnormalities in CLD patients and to study the association of hematological abnormalities with type and severity of CLD. This study was conducted as a facility based cross-sectional study at tertiary care centre on confirmed cases of chronic liver disease. Detailed clinical history along with clinical examination findings were recorded. All patients were then subjected to investigations. Mean age of patients with CLD was 48.8±16.9 years and majority of patients were males (76%). Anemia was observed in 71% cases with CLD whereas leukocytopenia and thrombocytopenia were noted in 21% and 56% cases respectively. Mean MCV, MCH, serum bilirubin and iron were significantly higher in cases with alcoholic liver disease whereas TIBC was significantly lower in ALD cases as compared to NALD cases (p&amp;#60;0.05). Mean hemoglobin, platelet levels, MCV, albumin and iron levels were significantly lower in cases with severe liver disease (Child Pugh Class C). However, serum bilirubin, prothrombin time and TIBC levels increased significantly with increase in severity of CLD (p&amp;#60;0.05). Hematological abnormalities particularly normocytic normochromic anemia and thrombocytopenia are common in cases with CLD, which might affect the prognosis of patients with CLD. Assessing the severity and type of anaemia is a useful tool for early initiation of the treatment in patients of CLD for reducing the morbidity and mortality. Early detection and treatment of haematological changes can prevent complications and reduce the mortality in CLD patients.

Oral Pathogenic Bacteria and the Oral-Gut-Liver Axis: A New Understanding of Chronic Liver Diseases.

Liver diseases have long been a prevalent cause of morbidity and mortality, and their development and progression involve multiple vital organs throughout the body. Recent studies on the oral-gut-liver axis have revealed that the oral microbiota is associated with the pathophysiology of chronic liver diseases. Since interventions aimed at regulating oral biological disorders may delay the progress of liver disease, it is crucial to better comprehend this process. Oral bacteria with potential pathogenicity have been extensively studied and are closely related to several types of chronic liver diseases. Therefore, this review will systemically describe the emerging role of oral pathogenic bacteria in common liver diseases, including alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cirrhosis, autoimmune liver diseases (AILD), and liver cancer, and bring in new perspectives for future research.

Meta‐analysis of the immunogenicity of standard and booster SARS‐CoV‐2 vaccination in patients with chronic liver disease and post‐liver transplantation

AbstractAimsPatients with liver disease may exhibit higher infection rates and mortality rates from coronavirus disease 2019 (COVID‐19) than healthy individuals, and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an effective prevention strategy. This meta‐analysis aimed to assess the effectiveness and safety of SARS‐CoV‐2 vaccines in patients with chronic liver disease (CLD) and post‐liver transplantation (LT).MethodsThe PubMed, Embase, and Cochrane databases were searched. A random‐effects model meta‐analysis was used to determine the seropositivity rates of SARS‐CoV‐2 antibodies, odds ratio (OR) compared with healthy controls (HC), risk ratio (RR) between the booster and standard vaccination regimen, and the rate of adverse reactions (ADR).ResultsIn the standard vaccination regimen analysis, 17 controlled articles were included for effectiveness analysis, and six articles for ADR analysis. The pooled seropositivity rates of SARS‐CoV‐2 antibodies in patients with CLD and post‐LT were 93.3% (95% confidence interval [CI]: 89.0%–97.6%) and 69.1% (95% CI: 63.0%–75.3%), respectively. Both rates were lower than those in HC (p &lt; 0.001). The differences remained significant after sorting by detection interval, vaccine type, antibody type, or CLD type. LT recipients showed much lower seropositivity rates of antibodies than patients with CLD (69.1% vs. 93.3%) or HC (OR: 0.055). The pooled total ADR rate of patients was 24.0% (95% CI: 16.2%–31.8%). In the booster vaccination regimen analysis, 11 prospective studies were enrolled, and the seropositivity rates of antibodies after the booster dose were increased by 27% compared with those of the standard vaccination regimen (RR: 1.27, 95% CI: 1.15–1.41, p &lt; 0.001).ConclusionPatients with CLD and post‐LT can gain protection against COVID‐19 from standard vaccines, demonstrating a potentially weaker immunogenic response than HC. Booster vaccines can compensate for this deficiency. Therefore, patients with CLD and post‐LT should be prioritized for receiving the COVID‐19 booster vaccine.

Transcription Factor Forkhead Box O1 Mediates Transforming Growth Factor-β1–Induced Apoptosis in Hepatocytes

Dysregulation of hepatocyte apoptosis is associated with several types of chronic liver diseases. Transforming growth factor-β1 (TGF-β1) is a well-known pro-apoptotic factor in the liver, which constitutes a receptor complex composed of TGF-β receptor I and II, along with transcription factor Smad proteins. As a member of the forkhead box O (Foxo) class of transcription factors, Foxo1 is a predominant regulator of hepatic glucose production and apoptosis. This study investigated the potential relationship between TGF-β1 signaling and Foxo1 in control of apoptosis in hepatocytes. TGF-β1 induced hepatocyte apoptosis in a Foxo1-dependent manner in hepatocytes isolated from both wild-type and liver-specific Foxo1 knockout mice. TGF-β1 activated protein kinase A through TGF-β receptor I-Smad3, followed by phosphorylation of Foxo1 at Ser273 in promotion of apoptosis in hepatocytes. Moreover, Smad3 overexpression in the liver of mice promoted the levels of phosphorylated Foxo1-S273, total Foxo1, and a Foxo1-target pro-apoptotic gene Bim, which eventually resulted in hepatocyte apoptosis. The study further demonstrated a crucial role of Foxo1-S273 phosphorylation in the pro-apoptotic effect of TGF-β1 by using hepatocytes isolated from Foxo1-S273A/A knock-in mice, in which the phosphorylation of Foxo1-S273 was disrupted. Taken together, this study established a novel role of TGF-β1→protein kinase A→Foxo1 signaling cascades in control of hepatocyte survival.

Liver-bone crosstalk in non-alcoholic fatty liver disease: Clinical implications and underlying pathophysiology.

Osteoporosis is a common complication of many types of chronic liver diseases (CLDs), such as cholestatic liver disease, viral hepatitis, and alcoholic liver disease. Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic liver disease, affecting almost one third of adults around the world, and is emerging as the dominant cause of CLDs. Liver serves as a hub for nutrient and energy metabolism in the body, and its crosstalk with other tissues, such as adipose tissue, heart, and brain, has been well recognized. However, much less is known about the crosstalk that occurs between the liver and bone. Moreover, the mechanisms by which CLDs increase the risk for osteoporosis remain unclear. This review summarizes the latest research on the liver-bone axis and discusses the relationship between NAFLD and osteoporosis. We cover key signaling molecules secreted by liver, such as insulin-like growth factor-1 (IGF-1), fibroblast growth factor 21 (FGF21), insulin-like growth factor binding protein 1 (IGFBP1), fetuin-A, tumor necrosis factor-alpha (TNF-α), and osteopontin (OPN), and their relevance to the homeostasis of bone metabolism. Finally, we consider the disordered liver metabolism that occurs in patients with NAFLD and how this disrupts signaling to the bone, thereby perturbing the balance between osteoclasts and osteoblasts and leading to osteoporosis or hepatic osteodystrophy (HOD).

Effects of Zhishi Daozhi Decoction on the intestinal flora of nonalcoholic fatty liver disease mice induced by a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease with a high incidence, and the situation is not optimistic. Intestinal flora imbalance is strongly correlated with NAFLD pathogenesis. Zhishi Daozhi Decoction (ZDD) is a water decoction of the herbs used in the classical Chinese medicine prescription Zhishi Daozhi Pills. Zhishi Daozhi Pills has shown promising hepatoprotective and hypolipidemic properties, but its specific mechanism remains unclear. Mice were fed on a high fat-rich diet (HFD) for ten weeks, and then the animals were administrated ZDD through oral gavage for four weeks. The serum liver function and blood lipid indexes of the mice were then tested using an automatic biochemical analyzer. H&E and Oil Red O staining were used to observe the pathological conditions of mice liver tissue, and 16S rRNA sequencing technology was used to analyze the changes in intestinal flora of mice. The concentration of short-chain fatty acids (SCFAs) in the gut of mice was analyzed by gas chromatography-mass spectrometry (GC-MS). The expression of tight junction (TJ) proteins between ileal mucosal epithelial cells was analyzed using the immunofluorescence technique. ZDD was found to reduce the bodyweight of NAFLD mice, reduce serum TG, CHO, ALT, and AST levels, reduce fat accumulation in liver tissue, make the structure of intestinal flora comparable to the control group, and increase the concentration of intestinal SCFAs. It was also found to increase the expression of TJ proteins such as occludin and ZO-1, making them comparable to the control group. ZDD has a therapeutic effect on NAFLD mice induced by HFD, which may act by optimizing the intestinal flora structure.

Insights on the Pathophysiology of the Progression to Decompensated Hepato-Splenic Schistosomiasis

Hepato-splenic schistosomiasis is the most important etiology of non-cirrhotic portal hypertension. It represents a particular type of chronic liver disease, which presents unique characteristics that differentiate it from those found in cirrhosis. The relative preservation of liver parenchyma despite portal fibrosis was thought to yield a more benign course of hepato-splenic schistosomiasis in terms of synthetic dysfunction and late decompensations. However, a wide range of immunologic and vascular modifications is responsible for an otherwise progressive liver disease resulting in decompensated condition frequently undistinguished from hepatic cirrhosis. A predominant Th2 immune response type, in which a fibrogenic profile of cytokines and interleukins such as IL-13, provides an immune-inflammatory background that favors fibrosis and its progression. Intra-hepatic vascular changes with portal vein branch derangement and abnormal vascular proliferation also contribute to continued disarray of the liver architecture resulting in decompensated disease frequently undistinguished from hepatic cirrhosis. This article will review immunologic and pathophysiological aspects of hepato-splenic schistosomiasis that might explain disease progression and severity.

Expression of Integrin β1, Focal Adhesion Kinase, and PDZ-Binding Motif in Human Liver Cirrhosis and Simple Steatosis

Background: Integrins are transmembrane mechanosensitive proteins that negatively contribute to the pathogenesis of different types of chronic liver disease and can activate focal adhesion kinase (FAK). Objectives: This study aimed to determine the hepatic integrin β1 and FAK mRNA as well as the transcriptional coactivator with PDZ-binding motif (TAZ) protein expressions in cirrhotic patients and simple steatosis. Methods: In this case–control study, liver tissues were collected from 30 cirrhotic patients with various etiologies (i.e., nonalcoholic steatohepatitis-, primary sclerosing cholangitis-, alcoholic-, autoimmune hepatitis [AIH]- and hepatitis B virus [HBV]/hepatitis C virus [HCV]-related cirrhosis [six per group]), liver samples with simple steatosis (n=6), and control liver tissues (n=9). Results: Integrin β1 gene expression was significantly up-regulated in all cirrhotic groups compared to control group (P&lt;0.05), with the exception of AIH cirrhosis. However, hepatic FAK gene expression and TAZ protein level in the cirrhotic groups were not significantly different than those in the control group. Furthermore, hepatic integrin β1 and FAK gene expressions as well as TAZ protein level in simple steatosis were significantly lower than those in nonalcoholic steatohepatitis (NASH) cirrhosis and control (P&lt;0.05). Conclusion: Integrin β1 was up-regulated in cirrhotic liver tissues. In addition, FAK, integrin β1, and TAZ were concordantly down-regulated in simple steatosis, and may have been involve in the steatosis development.

Correlation of image textures of a polarization feature parameter and the microstructures of liver fibrosis tissues

Mueller matrix imaging is emerging for the quantitative characterization of pathological microstructures and is especially sensitive to fibrous structures. Liver fibrosis is a characteristic of many types of chronic liver diseases. The clinical diagnosis of liver fibrosis requires time-consuming multiple staining processes that specifically target on fibrous structures. The staining proficiency of technicians and the subjective visualization of pathologists may bring inconsistency to clinical diagnosis. Mueller matrix imaging can reduce the multiple staining processes and provide quantitative diagnostic indicators to characterize liver fibrosis tissues. In this study, a fiber-sensitive polarization feature parameter (PFP) was derived through the forward sequential feature selection (SFS) and linear discriminant analysis (LDA) to target on the identification of fibrous structures. Then, the Pearson correlation coefficients and the statistical T-tests between the fiber-sensitive PFP image textures and the liver fibrosis tissues were calculated. The results show the gray level run length matrix (GLRLM)-based run entropy that measures the heterogeneity of the PFP image was most correlated to the changes of liver fibrosis tissues at four stages with a Pearson correlation of 0.6919. The results also indicate the highest Pearson correlation of 0.9996 was achieved through the linear regression predictions of the combination of the PFP image textures. This study demonstrates the potential of deriving a fiber-sensitive PFP to reduce the multiple staining process and provide textures-based quantitative diagnostic indicators for the staging of liver fibrosis.

The Association Between Serum Hyaluronic Acid Levels and Routine Liver Function Tests in Liver Fibrotic HCV Patients

Abstract Introduction/Objective Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Markers (NIM) of Liver Fibrosis, such as hyaluronic acid, help evaluate the stage of fibrosis in patients with liver fibrosis. This study aims to investigate whether or not there is a correlation between serum hyaluronic acid levels and liver function tests in patients who suffer from chronic HCV-induced liver fibrosis. Methods/Case Report This study was conducted on 118 (60 males and 58 females) patients recruited from Internal Medicine Dept., Mansoura University Hospitals, Egypt. The patients were diagnosed with chronic HCV-induced liver fibrosis. Also, we included 50 healthy comparable control subjects (27 males and 23 females). Routine laboratory tests such as AST, ALT, albumin, total bilirubin, and platelets count were performed. The APRI was calculated as [AST/ (upper limits of normal)/ platelets count 109/L]×100. The AST-ALT ratio was calculated as [AST/ ALT]. According to the manufacturer's instructions, the serum levels of hyaluronic acid were measured by radioimmunoassay. Results (if a Case Study enter NA) We observed a statistically significant positive correlation was found between serum hyaluronic acid levels and APRI (r=0.3, p=0.001), ALT (r=0.3, p=0.003), AST (r=0.3 and p=0.01), and total bilirubin (r=0.3 and p=0.002). Furthermore, there was a statistically significant negative correlation between serum hyaluronic acid levels and albumin (r= -0.43, p=0.0001), and platelets count (r= -0.4, p=0.0001). Conclusion The levels of hyaluronic acid in the body and the results of other liver function tests tend to rise in tandem, which suggests a significant relationship between the two. This may assist us in constructing an accurate picture of the patient's condition, which will lead to a more precise diagnosis.

Speed of sound index for liver steatosis estimation: a reliability study in normal subjects.

PURPOSE Non-alcoholic fatty liver disease (NAFLD) is the most widespread type of chronic liver disease in the Western countries. Ultrasound (US) is widely used for NAFLD staging. The Resona 7 US system (Mindray Bio-Medical Electronics Co., Ltd.) includes an image optimization and speed of ultrasound-related feature, Sound Speed Index (SSI). SSI is applied in a region of interest (ROI) that could potentially aid in tissue characterization. The purpose of this study is to evaluate the reliability of SSI on various examination parameters on normal subjects. METHODS Twenty normal subjects were examined by two radiologists performing SSI measurements in the liver in different ROI depths and sizes. Intraclass correlation coefficient (ICC) was calculated to measure intra- and inter-observer variability and inter-ROI variability. RESULTS For all ROIs and both radiologists, the mean inter-observer ICC was 0.62 and the mean intraobserver ICC was 0.52 and 0.79. The mean SSI values for all ROIs and examiners were in the range 1528.79-1540.16 m/s. CONCLUSION The results indicate that SSI can lead to reliable measurements on normal subjects, independent of ROI size but dependent on ROI placement. More studies processing NAFLD patients, utilizing reference methods of liver fat quantification either for reliability or correlation with SSI, should be performed to further investigate the relevance of the SSI as a potential biomarker in clinical practice for liver steatosis grading.

Do Non Alcoholic Fatty Liver Disease Patients Have more Severe Metabolic Syndrome

Background and goal: Alcohol-unrelated fatty liver disease (NAFLD) is a frequent type of chronic liver disease (CLD) that is rapidly spreading around the world. The study's primary goal is to evaluate the severity of metabolic syndrome in people with nonalcoholic fatty liver disease. Materials and methods: From January to July 2019, Shalimar Medical and Dental College in Lahore, Pakistan, conducted this cross-sectional study. Through the use of non-probability sampling, the data was gathered. 100 patients with hepatic cirrhosis provided the data. The participants in this study ranged in age from 20 to 60. For the serum examination of liver enzymes, blood was drawn. Results: A correlation between the severity of the metabolic syndrome and NAFLD was found in this study, which included data from 100 individuals with biopsy-proven NAFLD. The patients were 45.67 3.56 years old on average. Compared to the normal control (11,3.42), the ALT levels in the patients were 258.291.73, 79.6628.63, and 50.73 8.4 correspondingly. Patients with cirrhosis, alcoholic liver disease, and viral hepatitis all had considerably higher aspartate aminotransferase levels. The significant frequency elevated aminotransferases and of NAFLD in IR-obese adolescents, as well as the potential consequences for their health, are concluded. The strong connections between NAFLD and MetS encourage the screening for additional MetS co-morbidities.

Association of anxiety and depression with chronic liver diseases in patients with noncardiac chest pain: A cross-sectional study.

Causes of chest pain can vary from benign to life-threatening conditions, and in many cases not necessary of cardiac origin. A possible reason for noncardiac chest pain could be anxiety or depression caused by chronic liver diseases. The aim of this study was to investigate the association of anxiety and depression with chronic liver disease in patients with noncardiac pain.Patients with chest tightness or pain referred for treadmill exercise testing were recruited from a regional hospital in southern Taiwan. Medical records of the patients were used to define the presence and type of chronic liver disease. Multiple logistic regression analyses were conducted to assess the association of anxiety and depression with chronic liver disease.A total of 2537 patients with liver function test results and abdominal sonography data were analyzed, and 1965 patients showed a negative treadmill exercise testing. The mean age of these 1965 patients was 51.9 years and 54.2% were male. The prevalence of alcoholic liver disease, hepatitis B, hepatitis C, and fatty liver disease was 10.6%, 10.9%, 3.7%, and 27.0%, respectively. Results from multiple logistic regression analyses showed that the risk of anxiety (adjusted odds ratio [aOR] = 1.83, P < .001) and depression (aOR = 1.85, P < .001) was significantly higher in patients with alcoholic liver disease. Anxiety was significantly higher in patients with fatty liver disease (aOR = 1.30, P = .031), and the risk of depression was significantly higher in patients with chronic hepatitis C (aOR = 2.18, P = .005).In conclusion, in patients with noncardiac chest pain, alcoholic liver disease was significantly associated with anxiety and depression, while those with fatty liver and chronic hepatitis C were associated with anxiety and depression, respectively. Clinicians should be vigilant to these correlations in their practice.