Hepatic Fibrosis Stage Research Articles

Correlation of shear wave elastography with liver biopsy in children with Chronic Liver disease

Background & Objectives: Liver biopsy remains the gold standard for assessment of liver fibrosis; however, it is limited practically because of issues of sampling errors and invasiveness. This opens the way for other important non-invasive processes of diagnosis including the role and utilisation of Shear Wave Elastography in coming years for liver diseases. This post-hoc study will firstly aim to establish the correlation existing between the currently preferred gold standard liver biopsy and 2D-Shear Wave elastography’s diagnostic accuracy in paediatric patients presenting with suspected or confirmed liver disease. Methods: This retrospective study was conducted in Pakistan Kidney and Liver Institute and Research Center in Lahore, Pakistan from August 2017 to January 2024. In this analysis, 37 Paediatric patients with various liver diseases who underwent liver biopsy for autoimmune hepatitis, Budd-Chiari syndrome, Wilson disease and other liver-related pathologies were included. Results: Thirty-seven patients with a mean age of 10 years (ranging from 4–14 years) were enrolled. According to this study, sixteen out of thirty seven (43%) cases of chronic liver disease were caused by autoimmune hepatitis. Patients’ average liver stiffness as determined by SWE was 12.14 ± 0.75 kPa. According to elastography, the average liver stiffness in individuals with F0–F1 fibrosis was 6 ± 0.01 kPa, 7.67 ± 0.29 in stage F2, 8.62 ± 0.20 in stage F3, and 14.05 ± 3.69 kPa in stage F4. We discovered that the mean level of hepatic stiffness varied significantly depending on the degree of fibrosis (p = 0.0001). Conclusion: SWE gauges the liver tissue’s stiffness, which rises with fibrosis severity. Research has demonstrated that SWE, which is frequently equivalent to liver biopsy, has a high degree of accuracy in identifying and staging hepatic fibrosis. doi: https://doi.org/10.12669/pjms.41.2.9886 How to cite this: Imtiaz M, Khaqan MU, Mazhar M, Seerat I. Correlation of shear wave elastography with liver biopsy in children with Chronic Liver disease. Pak J Med Sci. 2025;41(2):585-589. doi: https://doi.org/10.12669/pjms.41.2.9886 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A Single-Chain Peptide Probe Targeting Pathological Collagen for Precise Staging of Hepatic Fibrosis by MR Imaging.

Hepatic fibrosis, a chronic liver response to injury with potential severe outcomes like cirrhosis and liver cancer, necessitates urgent noninvasive diagnostic techniques to halt disease progression. We herein for the first time developed a single-chain peptide probe targeting pathological collagen for in vivo magnetic resonance imaging (MRI) of hepatic fibrosis. The novel (GhypO)10 probe, distinguished by its unique monomeric conformation achieved through Pro to (2S,4S)-hydroxyproline (hyp) substitution and subsequent disruption of hydrogen bonding, exhibits selectivity for pathological collagen over its intact counterpart in connective tissues. Fluorescence imaging of liver specimens from fibrotic models displayed a discernible relationship between pathological collagen levels and fibrosis stage. Moreover, T1-weighted MR images post Gd-GhypO administration revealed progressive signal enhancement congruent with fibrosis severity, corroborated by a corresponding increase in the contrast-to-noise ratio (ΔCNR). Biodistribution analysis indicates that Gd-GhypO has low Gd retention in the main organs 24 h postinjection, ensuring the probe's safety for molecular imaging. The Gd-GhypO probe therefore emerges as a potent tool for the precise, noninvasive delineation of hepatic fibrosis stages, offering significant implications for the diagnosis and management of liver fibrosis.

Diagnostic performance of FibroTouch® in assessing hepatic steatosis and fibrosis in patients with metabolic dysfunction-associated steatotic liver disease: An Asian experience.

FibroTouch® has shown efficacy in staging hepatic fibrosis in patients with chronic viral hepatitis B, but its performance in assessing liver steatosis and fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients remains understudied. We aimed to evaluate the diagnostic performance of FibroTouch® in assessing steatosis and fibrosis in the MASLD population. Liver stiffness measurements and steatosis were assessed using FibroTouch® and FibroScan®, with FibroScan® as the reference standard. Pearson's correlation test evaluated correlations, and kappa statistics determined agreement between the two methods. Optimal cut-off values of FibroTouch® for predicting hepatic steatosis and fibrosis stages were determined through ROC curve analysis with the Youden index method. Strong correlations were observed between FibroTouch® UAP and FibroScan® CAP (rho=0.74) and LSM values (rho=0.87) (p < 0.001 for both) in a total of 380 patients. The mean CAP value for the entire cohort was 285 ± 51 dB/m, and the median LSM for the cohort was 5 .3kPa. The optimal FibroTouch® UAP cutoffs were 229 dB/m for S0 vs. S1, 267 dB/m for S1 vs. S2, and 294 dB/m for S2 vs. S3. For FibroTouch® LSM, the optimal cutoffs were 6.0 kPa for F0-F1 vs. F2, 7.9 kPa for F2 vs. F3, and 10.6 kPa for F3 vs. F4. Moreover, FibroTouch® effectively assessed hepatic steatosis and fibrosis in patients with different BMIs. FibroTouch® proved valuable in assessing hepatic steatosis and liver fibrosis staging in MASLD patients, enhancing its applicability in various clinical settings as a suitable and convenient option for MASLD patients.

The Bidirectional Relationship Between Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Cohort Study.

Introduction Type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) have shared pathophysiology. We aim to explore associations between these diseasesand the impact of T2D therapies on MASLD-related outcomes in a real-world population. Methods A retrospective cohort study included 153 patients with biopsy-proven MASLD. Health records were reviewed for biochemical or radiological changes over follow-up and compared by T2D status. The rate of incident T2D was determined, and in those with T2D, the changes over follow-up were compared by prescribed treatment. The statistical significance of changes over follow-up was evaluated by Student's t-test, and logistic regression was undertaken to determine the impact of variables on T2D development. Results One hundred and fifty-three patients were included with a mean follow-up of 48.0±22.0 months. Patients with T2D (n=73) were older than patients without T2D (n=80; 56.3 vs 51.9 years, p<0.05). Patients with T2D had a greater stage of hepatic fibrosis (2.6 vs 1.7, p<0.001). Nine (12.3%) patients with T2D and four (5.0%) without T2D died during follow-up (p=0.10). Patients without T2D had greater glycosylated haemoglobin (HbA1c) over follow-up (3.0 mmol/mol, p<0.01), and 21 (26.3%) developed T2D. Patients with T2D treated with sodium-glucose transporter-2 inhibitors (SGLT-2i) and/or glucagon-like peptide-1 receptor analogues (GLP-1RA)had a reduction in FibroScan®-controlled attenuation parameter (-33.7dB/m, p<0.001) but not liver stiffness measure. There were no significant FibroScan® changes in those receiving other treatments. Conclusions Patients with T2D had greater hepatic fibrosis, and one in four patients with MASLD developed T2D over four years. Treatment with SGLT-2i and/or GLP-1RA in patients with T2D is associated with improved measures of steatosisbut not fibrosis.

MASLD-F Algorithm to the Rescue: Improving Noninvasive Diagnosis of Hepatic Fibrosis in Patients With Severe Obesity.

The gold standard to stage hepatic fibrosis is with a liver biopsy. It is not without its drawbacks and is more challenging for patients with severe obesity. Noninvasive testing, including the fibrosis-4 (FIB-4) score and vibration-controlled transient elastography (VCTE), have begun to be increasingly used as initial screening methods.The applicability and accuracy of these noninvasive methods remain uncertain in patients with severe obesity and metabolic dysfunction-associated steatotic liver disease. Our study explored combining VCTE with lower FIB-4 cutoffs to improve concordance with biopsy in staging hepatic fibrosis in patients with metabolic dysfunction-associated steatotic liver disease and severe obesity undergoing bariatric surgery. A total of 632 patients with severe obesity underwent preoperative VCTE and intraoperative liver biopsy during bariatric surgery from January 2020 to August 2021. Variables collected included patient demographics, laboratory values, abdominal ultrasound, VCTE, and liver biopsy results. Analysis of variance 1-way test, χ2 tests, and Fisher exact tests were used for quantitative and qualitative variables, respectively. The 95% CIs for the mean FIB-4 scores were used to generate surrogate cutoff values. The VCTE and FIB-4 scores were integrated using an algorithm that utilized a dynamic decision-making process at each stage to find the values that would yield the highest concordance with liver biopsy. VCTE alone was in concordance with liver biopsy results in 59.7% of cases. Combining the proposed FIB-4 cutoff scores with VCTE led to an improved concordance with a liver biopsy of 88%. Our study demonstrated that accessible noninvasive testing has limitations alone but when combined, can improve staging of hepatic fibrosis.

Correlation Between Real-Time Shear Wave Elastography and Liver Serum Markers in Determining the Stage of Liver Fibrosis in Patients with Chronic Liver Diseases.

Introduction: Non-invasive methods aim to predict the stage of liver fibrosis in line with histological findings via biopsy. Shear wave elastography and serum markers are proven as accurate non-invasive methods for determining liver fibrosis as a modern non-invasive methods compared to liver biopsy in staging hepatic fibrosis. Aims: This study aims to determine the correlation between Shear Wave Elastography and indirect and direct serum markers of fibrosis when staging liver fibrosis. Material and methods: The study was conducted in the Clinic of Gastroenterohepatology, the Institute of Immunology and Human Genetics, and the Institute of Pathology between 2021 and 2023. The study comprises 70 patients with liver lesions, diagnosed based on clinical results, laboratory tests, and ultra-sound imaging. All patients underwent liver biopsy, classified according to Ishak and Metavir score as a reference method for diagnosing liver fibrosis. Real-time shear wave elastography was also performed as a non-invasive method and serum markers were checked for liver fibrosis. Findings: The statistical analysis indicated a positive correlation between the values of direct and indirect liver fibrosis markers and Shear Wave Elastography results. Conclusion: Our study has demonstrated that shear wave elastography has a significant positive correlation with biochemical markers of liver lesions and serum markers of liver fibrosis, whereas it has a negative correlation with platelets.

Proses Asuhan Gizi Terstandar pada Pasien dengan Autoimun dan Sirosis Hepatis

Liver cirrhosis is a pathological condition of the liver that defines the end stage of hepatic fibrosis. Liver cell damage will lead to disruption of the liver structure and increased vascularization, causing enlargement of blood vessels in the gastric and esophageal areas. Liver cirrhosis is often caused by history of infection with hepatitis B virus or hepatitis C virus. Other causes include a family history of liver disease, excessive alcohol consumption, and a history of autoimmune disease. Providing a liver diet as one of the standardized Nutrition Care Process (NCP) for this disease aims to achieve and maintain optimal nutritional status without burdening liver function. The purpose of the case study is to find out the process of standardized nutritional care process for patients with autoimmune and liver cirrhosis through providing a liver diet. The case study was conducted in September 2023 at patients in Hospital X Surabaya. After monitoring and evaluation, the patient’s energy, protein, fat, and carbohydrates intake domains increased even though they had not yet reached the fulfillment target (&lt;80%), the patient’s biochemistry domain was not received because the monitoring time was short, the patient’s physical/clinical condition continued to improve until the third day. The progress of the patient’s recovery over three days always increases. Starting with the stabilized appetite, the food intake received by patient increases so the patient’s physical and clinical condition continues to improve.

Drug treatments to prevent first decompensation in cirrhosis.

Cirrhosis is a prevalent condition affecting more than 100 million people globally and carrying significant morbidity and mortality related to the development of portal hypertension and hepatic decompensation. Current treatment is primarily targeted at identifying chronic liver disease early and preventing the progression of fibrosis by treating the underlying etiology of liver disease. Treatment options for patients with advanced fibrosis are limited, and the only drug class approved for the prevention of hepatic decompensation remains non-selective beta blockers. There are several pharmacological therapies being developed in both preclinical and clinical trials to explore their efficacy in preventing first hepatic decompensation. Most studies evaluate primary endpoints reflective of disease severity and portal hypertension, such as change in hepatic venous pressure gradient or fibrosis stage based on histology or imaging. While many drugs are being investigated, much work is still needed to identify treatment targets with effective outcomes in order to move the needle in the field of cirrhosis management. This narrative review will address the current state of cirrhosis therapies including potential new therapeutic targets as well as provide direction on future advancements that will improve our current treatment paradigm and lead to better outcomes for those burdened with cirrhosis.

Multiplex Collagen Fingerprinting for the Staging of Hepatic Fibrosis Using High-Precision Fluorescence-Guided SERS Imaging.

Hepatic fibrosis is a common chronic liver disease, and its severe progression can culminate in cirrhosis and hepatocellular carcinoma (HCC). Precise diagnosis and staging of hepatic fibrosis are essential to prevent liver cirrhosis and HCC. Simultaneous detection of multiplex collagen biomarkers within liver tissue is crucial for staging hepatic fibrosis. We herein for the first time constructed multiplex collagen fingerprinting for the staging of hepatic fibrosis using high-precision fluorescence-guided surface-enhanced Raman scattering (SERS) imaging. SERS/fluorescent probes, collectively referred to as SF, comprising silver nanoparticles (Ag NPs), Raman reporters, and FAM-labeled collagen targeting peptides. These probes exhibit exceptional aqueous dispersion and stability, attributed to the increased number of Asp residues in CTP. Meanwhile, SF probes, namely SF-I, SF-IV, and SF-D have demonstrated specific targeting of type I, type IV, and denatured collagen, respectively, within hepatic fibrotic tissues. The results from fluorescence-guided SERS imaging underscore the method's capacity for typing, localization, and quantification of collagen, thus providing novel insights into collagen's role in the development of hepatic fibrosis. The collagen fingerprinting strategy offers a potent toolkit for the multifaceted profiling of collagen superfamilies, holding significant implications for the precise staging of hepatic fibrosis.

Galectin 3-binding protein (LGALS3BP) depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1 (TGF-β1) availability and inhibits hepatocarcinogenesis.

Increased Galectin 3-binding protein (LGALS3BP) serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma (HCC). Considering the crucial role of transforming growth factor-β1 (TGF-β1) in the emergence of these diseases, the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling pathway. The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis (MASH) and HCC. Multiple omics techniques, such as RNA-sequencing, transposase-accessible chromatin-sequencing assay, and liquid chromatography-tandem mass spectrometry proteomics, were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 axis. The effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout mice. In patients with MASH and HCC, the levels of LGALS3BP and TGFB1 exhibited positive correlations. Stimulation of LGALS3BP by the inflammatory cytokine interferon α in HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1. Aggravated fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice, with increased TGFB1 levels. LGALS3BP directly bound to and assembled integrin αV, an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin cytoskeleton. The released TGF-β1 activated JunB transcription factor, which in turn promoted the TGF-β1 positive feedback loop. LGALS3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced fibrosis. Moreover, LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β1. LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway, making it a promising therapeutic target in TGF-β1-related diseases.

Effects of hepatic fibrosis on the quantification of hepatic steatosis using the controlled attenuation parameter in patients with chronic hepatitis B.

This study assessed the impact of hepatic fibrosis on the diagnostic performance of the controlled attenuation parameter (CAP) in quantifying hepatic steatosis in patients with chronic hepatitis B (CHB). CHB patients who underwent liver stiffness measurement (LSM) and CAP assessment using transient elastography before liver resection between 2019 and 2022 were retrospectively evaluated. Clinical data included body mass index (BMI) and laboratory parameters. The histologically determined hepatic fat fraction (HFF) and fibrosis stages were reviewed by pathologists blinded to clinical and radiologic data. The Pearson correlation coefficient between CAP and HFF was calculated. The diagnostic performance of CAP for significant hepatic steatosis (HFF ≥10%) was assessed using areas under the receiver operating curve (AUCs), stratified by fibrosis stages (F0-1 vs. F2-4). Factors significantly associated with CAP were determined by univariable and multivariable linear regression analyses. Among 399 CHB patients (median age 59 years; 306 men), 16.3% showed significant steatosis. HFF ranged from 0% to 60%. Of these patients, 9.8%, 19.8%, 29.3%, and 41.1% had fibrosis stages F0-1, F2, F3, and F4, respectively. CAP positively correlated with HFF (r=0.445, P&lt;0.001). The AUC of CAP for diagnosing significant steatosis was 0.786 (95% confidence interval [CI], 0.726 to 0.845) overall, and significantly lower in F2-4 (0.772; 95% CI, 0.708 to 0.836) than in F0-1 (0.924; 95% CI, 0.835 to 1.000) (P=0.006). Multivariable analysis showed that BMI (P&lt;0.001) and HFF (P&lt;0.001) significantly affected CAP, whereas LSM and fibrosis stages did not. CAP evaluations of significant hepatic steatosis are less reliable in CHB patients with significant or more advanced (F2-4) than with no or mild (F0-1) fibrosis.

Elevated ALT/AST ratio as a marker for NAFLD risk and severity: insights from a cross-sectional analysis in the United States.

The prevalence and incidence of Nonalcoholic fatty liver disease (NAFLD) are increasing worldwide, and NAFLD has emerged as a prominent global health concern. The link between serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio and NAFLD remains unclear. This study investigated the association between the ALT/AST ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population. We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 4753 participants. Subgroup analyses, stratified by age, gender, and body mass index (BMI), were performed, along with adjusted multivariable logistic regression analyses to evaluate the relationship between ALT/AST levels and the likelihood of NAFLD, liver steatosis, and hepatic fibrosis stage. A generalized additive model examined the non-linear relationship between ALT/AST and the probability of developing NAFLD. Among 4753 participants, 1508 (31.73%) were diagnosed with NAFLD. Significant positive correlations between ALT/AST and NAFLD risk were found across all models. In addition, the subgroup analysis by gender, age, and BMI suggested that ALT/AST showed a positive correlation with NAFLD. The ALT/AST ratio was positively correlated with the degree of liver steatosis and liver fibrosis. The correlation between ALT/AST and the incidence of NAFLD showed a non-linear pattern. In women, the non-linear trend is particularly evident, showing an inverted U-shaped curve with an inflection point of 1.302.A receiver operating characteristic (ROC) analysis showed that the predictive value of ALT/AST for NAFLD was better than that of traditional liver enzyme parameters. A higher ALT/AST ratio was independently associated with a significantly higher risk of NAFLD and liver fibrosis within American cohorts. This link is robust among females, children, and adolescents. ALT/AST ratio can be used as a simple and effective noninvasive biomarker to identify individuals with high risk of NAFLD.

NLRP3 inflammasome pathway involved in the pathogenesis of metabolic associated fatty liver disease

The prevalence of Metabolic-associated fatty liver disease (MAFLD) has been steadily increasing worldwide, paralleling the global epidemic of obesity and diabetes. It is estimated that approximately one-quarter of the global population is affected by MAFLD. Despite its high prevalence, MAFLD often goes undiagnosed due to the lack of specific symptoms in its early stages. However, as the disease progresses, it can lead to more severe liver-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, we aimed to investigate the expression levels of the nucleotide-binding oligomerization domain, leucine-rich repeat (LRR)—containing proteins (NLR) family pyrin domain-containing protein 3 [NLRP3] inflammasome pathway components, NLRP3 and interleukin 1β (IL-1β) genes in patients with MAFLD with various degrees of steatosis and fibrosis. Participants were classified into two equal groups; MAFLD group: consisted of 120 patients with different degrees of hepatic fibrosis and steatosis based on fibro scan results. The non-MAFLD group was comprised of 107 participants. Molecular analysis of pyrin domain-containing protein 3 and IL-1β relative gene expressions was performed in the blood of all participants, using Real-time quantitative polymerase chain reaction (RT-qPCR). Patients with post-MAFLD hepatic fibrosis had significantly higher relative gene expression levels of IL-1β and NLRP3; with IL-1β > 1.1 had AUC of 0.919, sensitivity of 88.33, specificity of 96.26, PPV of 96.4, and NPV of 88 and 92.3 accuracy (p value < 0.001). NLRP3 > 1.33 had a sensitivity of 97.5, specificity of 99.07, PPV of 99.2, NPV of 97.2, and 98.3 accuracy with an AUC of 0.991 (p value < 0.001) as predictors of post-MAFLD hepatic fibrosis.. A significant increase in the mean relative gene expression levels of both IL-1β and NLRP3 found in patients with early fibrosis (F0-F1-2); 31.97 ± 11.8 and 6.76 ± 2.18, respectively; compared with patients with advanced hepatic fibrosis stages (F2-F3); 2.62 ± 3.71 and 4.27 ± 2.99 (p < 0.001 each). The present study provides novel evidence for the possible involvement of IL-1β and NLRP3 inflammasome in metabolic-associated fatty liver disease pathogenesis and could be valid markers for the early detection of post-MAFLD hepatic fibrosis.

Conditional deletion of CEACAM1 in hepatic stellate cells causes their activation

ObjectivesHepatic CEACAM1 expression declines with advanced hepatic fibrosis stage in patients with metabolic dysfunction-associated steatohepatitis (MASH). Global and hepatocyte-specific deletions of Ceacam1 impair insulin clearance to cause hepatic insulin resistance and steatosis. They also cause hepatic inflammation and fibrosis, a condition characterized by excessive collagen production from activated hepatic stellate cells (HSCs). Given the positive effect of PPARγ on CEACAM1 transcription and on HSCs quiescence, the current studies investigated whether CEACAM1 loss from HSCs causes their activation. MethodsWe examined whether lentiviral shRNA-mediated CEACAM1 donwregulation (KD-LX2) activates cultured human LX2 stellate cells. We also generated LratCre + Cc1fl/fl mutants with conditional Ceacam1 deletion in HSCs and characterized their MASH phenotype. Media transfer experiments were employed to examine whether media from mutant human and murine HSCs activate their wild-type counterparts. ResultsLratCre + Cc1fl/fl mutants displayed hepatic inflammation and fibrosis but without insulin resistance or hepatic steatosis. Their HSCs, like KD-LX2 cells, underwent myofibroblastic transformation and their media activated wild-type HSCs. This was inhibited by nicotinic acid treatment which blunted the release of IL-6 and fatty acids, both of which activate the epidermal growth factor receptor (EGFR) tyrosine kinase. Gefitinib inhibition of EGFR and its downstream NF-κB/IL-6/STAT3 inflammatory and MAPK-proliferation pathways also blunted HSCs activation in the absence of CEACAM1. ConclusionsLoss of CEACAM1 in HSCs provoked their myofibroblastic transformation in the absence of insulin resistance and hepatic steatosis. This response is mediated by autocrine HSCs activation of the EGFR pathway that amplifies inflammation and proliferation.

Monoexponential and advanced diffusion-weighted imaging for hepatic fibrosis staging based on high inter-examiner reliability.

To determine the diagnostic efficiencies of multiple diffusion-weighted imaging (DWI) techniques for hepatic fibrosis (HF) staging under the premise of high inter-examiner reliability. Participants with biopsy-confirmed HF were recruited and divided into the early HF (EHF) and advanced HF (AHF) groups; healthy volunteers (HVs) served as controls. Two examiners analyzed intravoxel incoherent motion (IVIM) using the IVIM-DWI and diffusion kurtosis imaging (DKI) models. Intravoxel incoherent motion-DWI, DKI, and diffusion tensor imaging parameters with intraclass correlation coefficients (ICCs) of ≥0.6 were used to create regression models: HVs vs. EHF and EHF vs. AHF. We enrolled 48 HVs, 59 EHF patients, and 38 AHF patients. Mean, radial, and axial kurtosis; fractional anisotropy; mean, radial, and axial diffusivity; and α exhibited excellent reliability (ICCs: 0.80-0.98). Fractional anisotropy of kurtosis, f, and apparent diffusion coefficient showed good reliability (ICCs: 0.69-0.92). The real (0.58-0.67), pseudo- (0.27-0.76), and distributed diffusion coefficients (0.58-0.67) showed low reliability. In the HVs versus (vs.) EHF model, α (p=0.008) and ADC (p=0.011) presented statistical differences (area under curve [AUC]: 0.710). In the EHF vs. AHF model, α (p=0.04) and distributed diffusion coefficient (p=0.02) presented significant differences (AUC: 0.758). Under the premise of high inter-examiner reliability, DWI and IVIM-derived stretched-exponential model parameters may help stage HF.

Exploring the impact of excluding intrahepatic segmental vessels on liver stiffness measurement and advanced fibrosis diagnosis using magnetic resonance elastography.

The impact of excluding intrahepatic segmental vessels from regions of interest (ROIs) on liver stiffness measurement (LSM) via magnetic resonance elastography (MRE) remains uncertain. To determine the effect of excluding intrahepatic segmental vessels from ROIs on LSM obtained from MRE. This retrospective analysis included 95 participants who underwent successful two-dimensional gradient recalled-echo MRE before hepatic tumor resection (n = 49) or living liver donation (n = 46). The conventional LSM was determined by manually drawing ROIs on the elastogram within the 95% confidence region, staying 1 cm within the liver capsule and excluding large hilar vessels, the gallbladder, hepatic lesions, and artifacts. In addition, the modified LSM was determined by excluding intrahepatic segmental vessels. LSMs obtained by the two methods were compared with paired sample signed-rank test. Diagnostic performance for advanced fibrosis was calculated and compared using McNemar's test and Delong's test. The stage of hepatic fibrosis was assessed using surgical specimens by the METAVIR system. The modified LSM was larger than the conventional LSM (2.4 kPa vs. 2.2 kPa in reader 1; 2.7 kPa vs. 2.4 kPa in reader 2; P < 0.001). The modified LSM showed superior sensitivity (0.841 vs. 0.659 in reader 1; 0.864 vs. 0.705 in reader 2; P < 0.05) and area under the curve (0.901 vs. 0.820 in reader 1; 0.912 vs. 0.843 in reader 2; P < 0.05) for detecting advanced fibrosis (≥F3) than conventional LSM. The exclusion of intrahepatic segmental vessels from ROIs in MRE affected the LSM and enhanced diagnostic performance for advanced fibrosis.

Feasibility and performance of spin-echo EPI MR elastography at 3 Tesla for staging hepatic fibrosis in the presence of hepatic iron overload

PurposeTo assess the feasibility and performance of MR elastography (MRE) for quantifying liver fibrosis in patients with and without hepatic iron overload.MethodsThis retrospective single-center study analyzed 139 patients who underwent liver MRI at 3 Tesla including MRE (2D spin-echo EPI sequence) and R2* mapping for liver iron content (LIC) estimation. MRE feasibility and diagnostic performance between patients with normal and elevated LIC were compared.ResultsPatients with elevated LIC (21%) had significantly higher MRE failure rates (24.1% vs. 3.6%, p < 0.001) compared to patients with normal LIC (79%). For those with only insignificant to mild iron overload (LIC < 5.4 mg/g; 17%), MRE failure rate did not differ significantly from patients without iron overload (8.3% vs. 3.6%, p = 0.315). R2* predicted MRE failure with fair accuracy at a threshold of R2* ≥ 269 s−1 (LIC of approximately 4.6 mg/g). MRE showed good diagnostic performance for detecting significant (≥ F2) and severe fibrosis (≥ F3) in patients without (AUC 0.835 and 0.900) and with iron overload (AUC 0.818 and 0.889) without significant difference between the cohorts (p = 0.884 and p = 0.913). For detecting cirrhosis MRE showed an excellent diagnostic performance in both groups (AUC 0.944 and 1.000, p = 0.009).ConclusionSpin-echo EPI MRE at 3 Tesla is feasible in patients with mild iron overload with good to excellent performance for detecting hepatic fibrosis with a failure rate comparable to patients without iron overload.

Impact of Direct Acting Antivirals Therapy on Novel Fibrosis Index for Assessment of Hepatic Fibrosis in Comparison with AST to Platelet Ratio and Fibrosis-4 (FIB-4) Indices in Egyptian Patients with Chronic Hepatitis C Infection in Correlation with Fibroscan

Abstract Background Chronic viral infection causes multiple waves of inflammation and tissue repair which involves deposition of extracellular matrix resulting in scarring or progressive fibrosis over time and ultimately leading to liver cirrhosis. The introduction of DAAs has improved eradication rate of HCV and achievement of SVR. In addition to the high rates of sustained virological response (SVR), hepatic fibrosis may regress, and the risks of complications, such as hepatic failure and portal hypertension are reduced after SVRs, Stage of liver fibrosis in chronic HCV infection is a well-established factor that determines the severity of disease and associated complications. Numerous noninvasive fibrosis scores, imaging techniques and new serum fibrosis markers have been applied to evaluate the phases of liver fibrosis, and have mostly replaced liver biopsy Transient elastography (TE) is the most accurate method with high sensitivity and specificity for advanced fibrosis the aminotransferase (AST)/platelet ratio index (APRI) and the fibrosis-4 (FIB-4) scores are the most widely used in viral hepatitis C patients, particularly in those with significant fibrosis and cirrhosis. Objective The aim of this study is to evaluate Impact of Direct Acting Antivirals therapy on Novel fibrosis index for assessment of hepatic fibrosis in comparison with AST to Platelet ratio and fibrosis-4(FIB-4) indices in Egyptian patients with chronic hepatitis C infection in correlation with fibro scan. Patients and Methods This is a prospective Cohort clinical study performed on 100 Egyptian patients are ≥18 years of age who have chronic infection with hepatitis C who will be treated with combination of IFN-free DAAs (Sofosbuvir &amp; Daclatasvir ± Ribavirin) for 3 months. oral informed consent was taken from all patients included in the study. Results In the current study, there was significant regression of degree of fibrosis after treatment with DAAs in all patients achieving SVR by fibroscan, APR and fib4. novel fibrosis index is reliable and good tool in assessment of liver fibrosis in correlation to fibroscan, APRI and FIB4 especially significant fibrosis with the cut off value in prediction of hepatic fibrosis stage 4 was &amp;gt;3.1 and has sensitivity of 81.5% while the specificity was 74.1%. The positive predictive value was 66% while the negative predictive value was 86.8% Conclusion Novel fibrosis index has been found to be good reliable marker for assessment of liver fibrosis with high accuracy of predicting f4 fibrosis stage. There was significant marked reduction of fibrosis degree by fibroscan and non invasive indices (APRI &amp;FIB4) after treatment with directly acting antiviral in both cirrhotic and non cirrhotic patients regardless the treatment regimen used with improved overall liver function tests especially albumin level, liver enzymes, hemoglobin level and platelet count in patients who reached SVR.

Expression and predictive value of serum core fucosylated low molecular weight kininogen and alpha-galactosylated antibodies in patients with hepatic fibrosis.

Hepatic fibrosis is a common pathological basis for many chronic liver diseases and can progress to cirrhosis, a leading cause of mortality in liver diseases. Early identification and reversal of hepatic fibrosis are key in the treatment of chronic liver disease. This study aims to compare the expression levels of serum core fucosylated low molecular weight kininogen (LMWK-Fc) and alpha-galactosylated (α-Gal) antibodies in patients with hepatic fibrosis at different stages, and to evaluate their diagnostic efficacy for hepatic fibrosis. A retrospective analysis was conducted on 275 patients with chronic liver disease who visited the Department of Infectious Diseases at the Second Xiangya Hospital of Central South University between June 2022 and March 2023. Among these, 115 patients underwent liver biopsy. Based on the extent of collagen deposition and its impact on liver structure and microcirculation, patients were staged from 0 to 4: S0 (no significant collagen deposition in liver tissues; liver structure and microcirculation are normal), S1 (mild collagen deposition in liver tissues, with partial disruption of lobule structure, but microcirculation remains largely normal), S2 (moderate collagen deposition in liver tissues, with partial disruption of lobule structure and microcirculation), S3 (extensive collagen deposition in liver tissues, with substantial disruption of lobule structure and microcirculation), and S4 (development of cirrhosis, with heavy collagen deposition, complete disruption of lobule structure, and severe impairment of microcirculation). Patients were grouped as no fibrosis (S0), fibrosis (S1-S2), and significant fibrosis (S3-S4). For the 160 patients without liver biopsy, they were categorized based on liver stiffness measurement (LSM) value: no fibrosis (F0: LSM<7.3 kPa), fibrosis (F1-F2: LSM 7.3-12.4 kPa), and significant fibrosis (F3-F4: LSM>12.4 kPa). Demographic data (age, gender) and laboratory indicators (alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, alkaline phosphatase, alpha-fetoprotein, platelet count) were collected to calculate the fibrosis-4 index (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI). Serum LMWK-Fc and α-Gal antibodies were measured and compared across the groups, and their correlation with fibrosis severity was analyzed. The receiver operating characteristic (ROC) curve was used to assess the predictive value of serum LMWK-Fc and α-Gal antibody levels for hepatic fibrosis. Among the 160 patients without complete liver biopsy, serum α-Gal antibody and LMWK-Fc levels increased progressively from the no fibrosis group to the significant fibrosis group, with statistically significant differences (P<0.05). Among the 115 patients with liver biopsy, serum LMWK-Fc levels were significantly higher in the fibrosis group and the significant fibrosis groups compared with the no fibrosis group, and α-Gal antibody levels were significantly higher in the significant fibrosis group compared with the no fibrosis group and the fibrosis group (P<0.001, P=0.032, respectively). Univariate and multivariate linear regression analyses showed that hepatic fibrosis was correlated with gender and LMWK-Fc levels (both P<0.05), but not with age, α-Gal antibody levels, FIB-4, or APRI (all P>0.05). The expression levels of serum LMWK-Fc and α-Gal antibodies vary across different stages of hepatic fibrosis, suggesting a potential association with fibrosis progression. LMWK-Fc levels have a certain predictive value for the diagnosis of hepatic fibrosis.

3D-Printed SERS Chips for Highly Specific Detection of Denatured Type I and IV Collagens in Blood for Early Hepatic Fibrosis Diagnosis.

Hepatic fibrosis, the insidious progression of chronic liver scarring leading to life-threatening cirrhosis and hepatocellular carcinoma, necessitates the urgent development of noninvasive and precise diagnostic methodologies. Denatured collagen emerges as a critical biomarker in the pathogenesis of hepatic fibrosis. Herein, we have for the first time developed 3D-printed collagen capture chips for highly specific surface-enhanced Raman scattering (SERS) detection of denatured type I and type IV collagen in blood, facilitating the early diagnosis of hepatic fibrosis. Employing a novel blend of denatured collagen-targeting peptide-modified silver nanoparticle probes (Ag@DCTP) and polyethylene glycol diacrylate (PEGDA), we engineered a robust ink for the 3D fabrication of these collagen capture chips. The chips are further equipped with specialized SERS peptide probes, Ag@ICTP@R1 (S-I) and Ag@IVCTP@R2 (S-IV), tailored for the targeted detection of type I and IV collagen, respectively. The SERS chip platform demonstrated exceptional specificity and sensitivity in capturing and detecting denatured type I and IV collagen, achieving detection limits of 3.5 ng/mL for type I and 3.2 ng/mL for type IV collagen within a 10-400 ng/mL range. When tested on serum samples from hepatic fibrosis mouse models across a spectrum of fibrosis stages (S0-S4), the chips consistently measured denatured type I collagen and detected a progressive increase in type IV collagen concentration, which correlated with the severity of fibrosis. This novel strategy establishes a benchmark for the multiplexed detection of collagen biomarkers, enhancing our capacity to assess the stages of hepatic fibrosis.