Assessment Of Fibrosis Research Articles

Comparison of cytomorphology and histomorphology in myelodysplastic syndromes.

Gold standard for the establishment of the diagnosis of myelodysplastic syndromes (MDS) are cytomorphological features of hematopoietic cells in peripheral blood and bone marrow aspirates. There is increasing evidence that bone marrow histomorphology not only aids in the diagnosis of MDS but can provide additional prognostic information, particularly through assessment of fibrosis and cellularity. However, there is only sparse data on direct comparison between histological and cytomorphological findings within the same MDS patient cohort. Therefore, we performed such an analysis under exceptionally well-standardized conditions. We reexamined biopsy material of 128 patients from the Düsseldorf MDS registry who underwent bone marrow trephine biopsy (in addition to bone marrow aspiration) at the time of diagnosis, addressing the following items: a. Analysis of concordance of diagnoses made by histology and cytomorphology b. Analysis of additional information by histology with regard to the diagnosis and prognosis. The respective biomaterials were available at our institution and had been processed according to unchanged protocols between 1992 and 2010. Fresh histopathological sections were obtained from the tissue blocks, stained under identical conditions and re-assessed by a designated expert pathologist (C.B.) without knowledge of the previous histopathological report or the respective cytomorphological diagnosis. The latter, likewise, was uniformly made by the same expert cytomorphologist (U.G.). Histopathology of bone marrow trephine biopsies reliably captured the diagnosis of MDS. Assignment to the diagnostic WHO subgroup was not entirely concordant with cytomorphology, mainly due to incongruences between the proportion of CD34-positive cells on histopathology and the cytomorphological blast count. Histopathology provided additional diagnostic and prognostic information with high diagnostic and prognostic significance, such as fibrosis. Likewise, histopathology allowed more reliable estimation of bone marrow cellularity.

The first MASH drug therapy on the horizon: Current perspectives of resmetirom.

The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) poses a significant global health challenge, affecting over 30% of adults worldwide. MASLD is linked to increased mortality rates and substantial healthcare costs, primarily driven by its progression to metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver complications including cirrhosis and hepatocellular carcinoma. Despite its growing burden, effective pharmacotherapy for MASLD/MASH has been lacking until the recent conditional approval of resmetirom by the FDA. Resmetirom, a liver-targeted thyroid hormone receptor-β selective drug, has shown promise in clinical trials for treating non-cirrhotic MASH with moderate to advanced fibrosis. It has demonstrated efficacy in reducing hepatic fat content, improving liver histology (both MASH resolution and fibrosis improvement), and ameliorating biomarkers of liver damage without significant effects on body weight or glucose metabolism. Notably, resmetirom also exhibits favourable effects on circulating lipids, potentially reducing cardiovascular risk in MASLD/MASH patients. The safety profile of resmetirom appears acceptable, with gastrointestinal adverse events being the most common, though generally mild or moderate. However, long-term surveillance is warranted to monitor for potential risks related to thyroid, gonadal, or bone diseases. Clinical implementation of resmetirom faces challenges in patient selection and monitoring treatment response, and will heavily rely on non-invasive tests for liver fibrosis assessment. Nonetheless, resmetirom represents a landmark breakthrough in MASLD/MASH treatment, paving the way for future therapeutic strategies aiming to mitigate the multifaceted risks associated with this complex metabolic liver disease.

Quantitative analysis of liver standardized uptake value repeatability in SPECT/CT implications for clinical practice

Purpose. The aim of this study was to assess the repeatability of the SUV normalized by liver volume (SUVL) between two liver receptor SPECT/CT studies performed on different days in patients with ICG-R15 values within normal range. Methods. 935 patients who underwent liver receptor scintigraphy between January 2010 and August 2018 were included. Patients who underwent liver resection, hepatic arterial embolization or had ICG-R15 >10% between scans were excluded, and 38 patients were finally included in the analysis. The repeatability of SUVL between scans was assessed using the intraclass correlation coefficient (ICC) (1.1) between SUVLmax, SUVLpeak and SUVLmean at the first and second scan and the additive and proportional errors from the Bland-Altman analysis. Results. In ICC (1,1), SUVLmax, SUVLpeak and SUVLmean were all greater than 0.8, indicating almost perfect repeatability; neither additive nor proportional errors were observed in the Bland-Altman analysis. Conclusions. In patients with ICG-R15 values within the normal range, the SUV Liver (SUVL) between two liver receptor SPECT/CT studies performed on different days was repeatability over time. It was suggested that the SUVL of liver receptor scintigraphy could be an indicator that could be used for follow-up over time in the assessment of liver fibrosis.

Contemporary Imaging Assessment of Strictures and Fibrosis in Crohn Disease, With Focus on Quantitative Biomarkers: From the AJR Special Series on Imaging of Fibrosis.

Patients with Crohn disease commonly have bowel strictures develop, which exhibit varying degrees of inflammation and fibrosis. Differentiation of the distinct inflammatory and fibrotic components of strictures is key for the optimization of therapeutic management and for the development of antifibrotic drugs. Cross-sectional imaging techniques, including ultrasound, CT, and MRI, allow evaluation of the full thickness of the bowel wall as well as extramural complications and associated mesenteric abnormalities. Although promising data have been reported for a range of novel imaging biomarkers for detection of fibrosis and quantification of the degree of fibrosis, these biomarkers lack sufficient validation and standardization for clinical use. Additional methods, including PET with emerging radiotracers, artificial intelligence, and radiomics, are also under investigation for stricture characterization. In this review, we highlight the clinical relevance of identifying fibrosis in Crohn disease, review the histopathologic aspects of strictures in Crohn disease, summarize the morphologic imaging findings of strictures, and explore contemporary developments in the use of cross-sectional imaging techniques for detecting and characterizing intestinal strictures, with attention given to emerging quantitative biomarkers.

Radiology: Cardiothoracic Imaging Highlights 2023.

Radiology: Cardiothoracic Imaging publishes novel research and technical developments in cardiac, thoracic, and vascular imaging. The journal published many innovative studies during 2023 and achieved an impact factor for the first time since its inaugural issue in 2019, with an impact factor of 7.0. The current review article, led by the Radiology: Cardiothoracic Imaging trainee editorial board, highlights the most impactful articles published in the journal between November 2022 and October 2023. The review encompasses various aspects of coronary CT, photon-counting detector CT, PET/MRI, cardiac MRI, congenital heart disease, vascular imaging, thoracic imaging, artificial intelligence, and health services research. Key highlights include the potential for photon-counting detector CT to reduce contrast media volumes, utility of combined PET/MRI in the evaluation of cardiac sarcoidosis, the prognostic value of left atrial late gadolinium enhancement at MRI in predicting incident atrial fibrillation, the utility of an artificial intelligence tool to optimize detection of incidental pulmonary embolism, and standardization of medical terminology for cardiac CT. Ongoing research and future directions include evaluation of novel PET tracers for assessment of myocardial fibrosis, deployment of AI tools in clinical cardiovascular imaging workflows, and growing awareness of the need to improve environmental sustainability in imaging. Keywords: Coronary CT, Photon-counting Detector CT, PET/MRI, Cardiac MRI, Congenital Heart Disease, Vascular Imaging, Thoracic Imaging, Artificial Intelligence, Health Services Research © RSNA, 2024.

LiverRisk score: An accurate, cost-effective tool to predict fibrosis, liver-related, and diabetes-related mortality in the general population

Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n= 3,770), along with the NHANES follow-up cohort (n= 25,317) and the UK Biobank follow-up cohort (n= 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10kPa were defined as compensated advanced chronic liver disease (cACLD). Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).

Imaging Evaluation of Clinical and Subclinical Myocarditis in Multisystem Inflammatory Syndrome of Children with COVID-19 Using Cardiac Magnetic Resonance: The Results and Prognosis

Background: Coronavirus disease 2019 (COVID-19) has emerged as the most significant health crisis in recent years, leading to over 6 million deaths globally due to the disease. Objectives: Given the prevalence of multisystem inflammatory syndrome in children (MISC) following the COVID-19 pandemic, this study aims to examine the imaging findings and prognoses of clinical and subclinical myocarditis in children with MISC through cardiac magnetic resonance (CMR) imaging. Patients and Methods: This prospective cohort study carried out over eighteen months from May 2021 to November 2022, included 14 patients who underwent CMR imaging. A census of all eligible patients during the study period served as the sampling method. Inclusion criteria were patients with confirmed COVID-19 infection through serological tests, polymerase chain reaction (PCR), or recent exposure to COVID-19 patients. Exclusion criteria included patients with a history of congenital heart disease (CHD) or pulmonary disease. Additional diagnostic tests performed included blood sample tests, chest X-ray (CXR), electrocardiogram (ECG), and echocardiography. CMR imaging was conducted on patients with cardiac involvement. A diagnosis of myocardial inflammation was made if a patient met at least two of the Lake Louise Criteria. The Chi-square, Fisher's exact, and Mann-Whitney tests were used to examine the relationship between quantitative variables and treatment outcomes. Additionally, the Wilcoxon signed rank, and McNemar’s tests assessed changes in echocardiography findings from admission to follow-up. A significance level of 0.05 was set. Results: Among the 14 patients studied, 8 (57.10%) were girls and 6 (42.90%) were boys. The average age was 6.03 ± 3.71 years. The median time to CMR imaging after symptom onset was 4 weeks (interquartile range (IQR): 2 - 12, range: 30). Global function assessment using left ventricular ejection fraction (LVEF) showed that 5 (35.70%), 3 (21.40%), and 6 (42.90%) patients had normal function, mild dysfunction, and significant LV dysfunction, respectively. 71.40% of patients who recovered had mild tricuspid regurgitation (TR) and no cardiomegaly. Significant differences in mean values of polymorphonuclear neutrophil (PMN) (37.71 ± 11.75 vs. 81.44 ± 13.06), lymphocytes (48.71 ± 20.08 vs. 12.51 ± 7.26), hemoglobin (Hb) (12.60 ± 1.55 vs. 10.10 ± 1.62), mean corpuscular volume (MCV) (85.90 ± 5.67 vs. 79.37 ± 5.23), erythrocyte sedimentation rate (ESR) (8.86 ± 13.60 vs. 30.29 ± 21.33), and C-reactive protein (CRP) (18.91 ± 27.25 vs. 100.57 ± 85.67) were observed between non-recovered and recovered patients, respectively (P < 0.05). However, no statistically significant association was found between other variables, including N-terminal pro–B-type natriuretic peptide (NT-proBNP), D-dimer, and Troponin I (TPI), with treatment outcomes (P > 0.05). Conclusion: Our findings indicate that a negative COVID-19 test does not exclude an established clinical COVID-19 infection in children with MISC. The results suggest that all children with MISC and a history of COVID-19 infection should undergo assessment for myocardial fibrosis, regardless of ejection fraction (EF) as determined by Echocardiography, laboratory tests, and COVID-19 test results. Strain analysis, conducted during both the acute phase and subsequent follow-ups through CMR imaging or Echocardiography, is recommended to enhance the understanding of the prognosis.

Assessment and Risk Prediction of Chronic Kidney Disease and Kidney Fibrosis Using Non-Invasive Biomarkers.

Effective management of chronic kidney disease (CKD), a major health problem worldwide, requires accurate and timely diagnosis, prognosis of progression, assessment of therapeutic efficacy, and, ideally, prediction of drug response. Multiple biomarkers and algorithms for evaluating specific aspects of CKD have been proposed in the literature, many of which are based on a small number of samples. Based on the evidence presented in relevant studies, a comprehensive overview of the different biomarkers applicable for clinical implementation is lacking. This review aims to compile information on the non-invasive diagnostic, prognostic, and predictive biomarkers currently available for the management of CKD and provide guidance on the application of these biomarkers. We specifically focus on biomarkers that have demonstrated added value in prospective studies or those based on prospectively collected samples including at least 100 subjects. Published data demonstrate that several valid non-invasive biomarkers of potential value in the management of CKD are currently available.

A regular screening for hepatitis delta virus among chronic hepatitis B carriers improves the diagnostic of this infection and of subsequent cirrhosis development.

The prevalence of Hepatitis Delta Virus (HDV) is underestimated and the assessment of fibrosis is recommended for this infection. We tested the diagnostic impact of an annual screening for HDV serology in Hepatitis B Surface Antigen (HBs Ag) chronic carriers and followed the progression of fibrosis in these patients. Between January 2014 and October 2021, we annually tested all chronic HBs Ag-positive patients for HDV antibody (HDV Ab). Each HDV Ab positive patient underwent annually repeated elastometry. Patients with detectable HDV RNA levels (group 1) were compared to those with undetectable HDV RNA (group 2). We identified 610 chronic HBs Ag-positive patients, and repeated screening for HDV Ab was performed in 534 patients. Sixty (11%) patients were HDV Ab positive at baseline and were considered as "coinfected". Seven cases of HDV superinfection were diagnosed through repeated screening. In co-infected patients, cirrhosis was initially diagnosed in 12/60 patients and developed in six patients during follow-up. HDV RNA PCR was performed in 57/67 patients and 27 had detectable levels (group 1). Cumulative incidence of cirrhosis at 7years was 13.8% (95% CI 0-30) in group 1 and 0 (95% CI 0-0) in group 2 (p=0.026). A systematic screening for HDV in chronic HB Ag carriers revealed a high prevalence of HDV Ab. Repeated serological screening enables the diagnosis of superinfections in asymptomatic patients. Regular assessment of fibrosis using elastometry leads to the identification of incidental cirrhosis in patients with detectable HDV RNA.

Abstract 3774: Evaluation of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma

Abstract Introduction and Objectives: The incidence of hepatocellular carcinoma (HCC) has almost tripled since the early 1980s in the United States where it is the fastest rising cause of cancer-related deaths. Advanced liver fibrosis and cirrhosis are ones of major risk factors for HCC. The recent evidence demonstrates that successfully treating the cause of early to moderate hepatic fibrosis may reverse most. For this reason, detecting hepatic fibrosis in an early stage is crucial. Liver biopsy is currently the gold standard for the assessment of hepatic fibrosis in clinical practice. Thus, there is an urgent clinical need for the development of non-invasive blood-based tests because of its ease of obtaining biological material. Previously, we developed FibraChek™, non-invasive blood-based tests. In this study, we tested the performance of FibraChek™ on detecting hepatic fibrosis and HCC in the US. Methods: The performance of FibraChek™ was evaluated in a single-institutional cohort of 14 prospectively collected subjects presenting for chronic liver disease (NAFLD/NASH) patients with hepatic fibrosis, 19 prospectively collected subjects diagnosed with HCC, and 12 prospectively collected controls from the US. The algorithm uses weighted value of the 5 biomarkers: AST, ALT, Platelet, Taurocholic Acid (TCA) & Tyrosine plus age to derive a risk score. The ability of the test to identify patients harboring hepatic fibrosis or HCC was assessed. Hepatic fibrosis status was confirmed by tissue biopsy or definitive surgery. Diagnostic performance was assessed using AUC. Results: FibraChek™ provided an AUC of 0.923 with an overall sensitivity of 93.9%, specificity of 81.8%, NPV 91.2% and PPV 81.8%. Interestingly, risk scores in HCC cohort indicated higher than those in patients with hepatic fibrosis. Thus, FibraChek™ may be also able to use for HCC detection. Conclusions: Serum levels of a biomarker panel enabled the accurate discrimination of hepatic fibrosis and controls. The FibraChek™ test can achieve the easy, efficient, and accurate detection of hepatic fibrosis and HCC in a non-invasive patient setting. Citation Format: Sunao Tanaka, Guoxiang Xie, Hideki Furuya, Wei Jia, Charles J. Rosser. Evaluation of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3774.

Abstract 6383: Targeting radiation-induced fibrosis: Exploring promising therapeutic avenues and innovative assessment methods

Abstract Introduction: Radiation therapy is a vital cancer treatment for nearly 50% of patients, yet it poses a significant challenge in the form of radiation-induced fibrosis (RF). RF affects about 60% of those undergoing radiation, leading to painful scarring from excessive collagen accumulation. In head and neck cancer patients, as an example, RF reduces tissue flexibility, causing limited neck mobility and impaired swallowing. Furthermore, approximately 30% of patients also face disease recurrence post-radiation, with RF increasing surgical complications. Our laboratory previously identified the role of reduced fatty acid oxidation in RF (Zhao et al; Nat Metab;1(1):147 2019), offering a promising avenue for future drug development. We described the potential therapeutic benefit of caffeic acid phenethyl ester (CAPE) in countering pro-fibrotic metabolic changes. Our current objective is to develop more effective lead compounds to mitigate RF. Methods: Collagen expression, utilized as a surrogate marker for fibrosis, was quantified using ELISA, Western blot analysis, and RT-qPCR. Metabolic changes were assessed by examining the expression levels of PPARG and CD36. CAPE-like analogs were derived from an in-house collection, a commercially available library, and structure-activity relationship (SAR) analyses. In vivo, RF was induced in the hindlimbs of mice through exposure to 40 Gy, followed by weekly X-ray evaluations of hindlimb angles for 16 weeks. During X-ray assessments, both hindlimbs were subjected to a 5 g weight to enable measurement of the joint angle between the femur and tibia (wherein higher acute angles were a measure of worsening fibrosis). Skin samples from irradiated and unirradiated limbs were collected for the evaluation of collagen deposition, utilizing Picro Sirius staining followed by polarized microscopy. Results: Amongst 200 newly synthesized analogs, approximately one-third successfully reduced collagen secretion in human primary dermal fibroblasts. The most promising compounds exhibited a half-maximum inhibition concentration (IC50) for collagen secretion from 1 to 5µM. They also decreased intracellular collagen production and gene expression, associated with upregulation of PPARG and CD36 transcripts. The joint angle measurements in vivo revealed three distinct phases in the development of dermal fibrosis: 1) inflammatory; 2) recovery; and 3) fibrotic phases. Conclusions: We have successfully synthesized novel and potent analogs of CAPE which were able to reduce secretion of collagen. Furthermore, a novel method for the in vivo assessment of fibrosis was also developed. This innovative approach will facilitate the detailed assessments of future compounds capable of reducing collagen deposition in vivo, thereby providing an innovative avenue to mitigate one of the most pressing late normal tissue toxicities of radiation therapy. Citation Format: Pierre-Antoine Bissey, Leonardo Massignan, Ross Mancini, Wei Shi, Justin Williams, Mark Reed, Kenneth W. Yip, Fei-Fei Liu. Targeting radiation-induced fibrosis: Exploring promising therapeutic avenues and innovative assessment methods [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6383.

Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

AASLD Practice Guideline on imaging-based noninvasive liver disease assessment of hepatic fibrosis and steatosis.

AASLD Practice Guideline on imaging-based noninvasive liver disease assessment of hepatic fibrosis and steatosis.

AASLD Practice Guideline on blood-based noninvasive liver disease assessment of hepatic fibrosis and steatosis.

AASLD Practice Guideline on blood-based noninvasive liver disease assessment of hepatic fibrosis and steatosis.

18F] AlF-NOTA-FAPI-04 PET/CT for non-invasive assessment of tubular injury in kidney diseases.

[18F] AlF-NOTA-FAPI-04 is a novel positron emission tomography (PET) ligand, which specifically targets fibroblast activation protein (FAP) expression as a FAP inhibitor (FAPI). We analysed the diagnostic value of [18F] AlF-NOTA-FAPI-04 PET/CT for the non-invasive assessment of kidney interstitial inflammation and fibrosis in different renal pathologies. Twenty-six patients (14 males and 12 females; mean age, 50.5±16.5 years) with a wide range of kidney diseases and 10 patients (six males and four females; mean age, 55.4±8.6 years) without known evidence of renal disease as disease controls underwent [18F] AlF-NOTA-FAPI-04 PET/CT imaging. Kidney tissues obtained from kidney biopsies were stained with haematoxylin and eosin, periodic acid-Schiff, Masson's trichome, and periodic acid-silver methenamine. Immunohistochemical staining was also performed to assess the expression of α-smooth muscle actin (αSMA) and FAP. Renal parenchymal FAPI uptake reflected by maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) measurements on PET/CT was analysed against pathohistological findings. We found that renal parenchymal FAPI uptake was significantly higher in patients with various kidney diseases than in control patients in this study (SUVmax=4.3±1.8vs 1.9±0.4, SUVmean=3.9±1.7vs 1.5±0.4, respectively; all P<0.001). All kidney diseases, both in acute and chronic kidney disease, had increased renal parenchymal uptake to varying degrees. The correlation analysis indicated a positive association between the SUVmax and the tubulointerstitial inflammation (TII), interstitial fibrosis and tubular atrophy (IF/TA), and TII+IF/TA scores (r=0.612, 0.681, and 0.754, all P<0.05), and between the SUVmean and the TII, IF/TA, and TII+IF/TA scores (r=0.603, 0.700, and 0.748, all P<0.05). Furthermore, we found significant positive correlations between both SUVmax and the SUVmean with SMA and FAP staining scores (r=0.686 and 0.732, r=0.667 and 0.739, respectively; both P<0.001). [18F] AlF-NOTA-FAPI-04 PET/CT is clinically available for the comprehensive and non-invasive assessment of tubular injury in various kidney diseases.

Validation of FIB-6 score in assessment of liver fibrosis in chronic hepatitis B.

We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability.

Intravoxel incoherent motion assessment of liver fibrosis staging in MASLD.

Partial correlation analysis was performed to account for the interference of steatosis changes and inflammatory factors, to determine the true correlation between fibrosis and IVIM parameters (Dfast, Dslow, and F), and to evaluate the diagnostic efficacy of IVIM for liver fibrosis. A total of 106 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) examined by IVIM from November 2016 to November 2023 at our hospital were retrospectively included. Preliminary analysis of each IVIM parameter and correlations with pathological findings were performed using Spearman correlation analysis, and partial correlation analysis was used to exclude the interference of other pathological factors, thus yielding the true correlations between IVIM parameters (Dfast, Dslow, and F) and pathology. The diagnostic efficacy of IVIM parameters for diagnosing MASLDwas assessed via receiver operating characteristic (ROC) curve analysis. Spearman correlation analysis of all the IVIM parameters revealed correlations with steatosis, lobular inflammation, and ballooning. Partial correlation analysis indicated that Dfast was correlated with the pathological fibrosis stage (r = - 0.593, P < 0.001), Dslow was correlated with the pathological steatosis score (r = - 0.313, P < 0.05), and F was correlated with the pathological fibrosis stage and steatosis score (r = - 0.456 and 0.255, P < 0.001 and P < 0.05). In the diagnosis of hepatic fibrosis, significant hepatic fibrosis, advanced liver fibrosis and cirrhosis, Dfast achieved areas under the ROC curve of 0.763, 0.801, 0.853, and 0.897, respectively. The threshold values for diagnosing different fibrosis stages using Dfast (10-3 mm2/s) were 57.613, 54.587, 52.714, and 51.978, respectively. According to our partial correlation analysis, there was a moderate correlation between Dfast and F according to fibrosis stage, and Dfast was not influenced by inflammation or steatosis when diagnosing fibrosis in MASLD patients. A relatively close Dfast threshold is insufficient for accurately and noninvasively assessing various stages of MASLD fibrosis. In clinical practice, this approach can be considered an alternative method for the preliminary assessment of fibrosis in MASLD patients.

Evaluation of aspartate aminotransferase to platelet ratio index and fibrosis 4 score for selecting patients with chronic hepatitis B to perform liver fibrosis assessment by transient elastography in resource-limited areas

Evaluation of aspartate aminotransferase to platelet ratio index and fibrosis 4 score for selecting patients with chronic hepatitis B to perform liver fibrosis assessment by transient elastography in resource-limited areas

Assessment of hepatic fibrosis with non-invasive indices in subjects with diabetes before and after liver transplantation.

One of the most common complications of cirrhosis is diabetes, which prevalence is strictly related to severity of hepatopathy. Actually, there are no data on the persistence of post-transplant glucose abnormalities and on a potential impact of diabetes on development of fibrosis in the transplanted liver. To this aim, we evaluated liver fibrosis in cirrhotic subjects before and after being transplanted. The study included 111 individuals who had liver transplantation. The assessment was performed before and two years after surgery to investigate a potential impact of the persistence of diabetes on developing de novo fibrosis in the transplanted liver. The degree of fibrosis was assessed using the Fibrosis Index Based on 4 Factors (FIB-4) and the Aspartate to Platelet Ratio Index (APRI). At pre-transplant evaluation, 63 out of 111 (56.8%) subjects were diabetic. Diabetic subjects had higher FIB-4 (Geometric mean, 95% confidence interval: 9.74, 8.32-11.41 vs 5.93, 4.71-7.46, P<0.001) and APRI (2.04, 1.69-2.47 vs 1.18, 0.90-1.55, P<0.001) compared to non-diabetic subjects. Two years after transplantation, 39 out of 111 (35.1%) subjects remained with diabetes and continued to show significantly higher FIB-4 (3.14, 2.57-3.82 vs 1.87, 1.55-2.27, P<0.001) and APRI (0.52, 0.39-0.69 vs 0.26, 0.21-0.32, P<0.001) compared to subjects without diabetes. Thus, persistence of diabetes after surgery is a possible risk factor for an evolution to fibrosis in the transplanted liver, potentially leading to worsened long-term outcomes in this population.

Insulin-like Growth Factor Binding Proteins and Cellular Senescence Are Involved in the Progression of Non-Alcoholic Fatty Liver Disease and Fibrosis in a Mouse Model.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBPs) are a family of secreted proteins involved in senescence and scarring, mainly synthetized in the liver. Here, we aimed to study the association of IGFBPs and their induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: A total of 16-week-old male C57BL/6 mice weighing 23 ± 3 g were fed either methionine/choline-deficient (MCD) or control diet for 2, 8, or 12 weeks. Blood and liver samples were collected, and a histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in the liver and serum. Data were expressed as mean ± SD and analyzed by a one-way ANOVA followed by Tukey's test. Lineal regression models were applied for NAFLD and fibrosis progression. p < 0.05 was considered significant. Results: IGFBP-1 and -2 were increased in serum during NAFLD. IGFBP-7 was significantly increased in the serum in NASH compared with the controls. Senescence increased in NAFLD. Serum and liver IGFBP-7 as well as SA-β-gal activity increased as fibrosis progressed. Both IGFBP-7 and cellular senescence were significantly higher during NAFLD and fibrosis in MCD-fed mice. Conclusions: IGFBP-1, -2, and -7, through their consequent senescence, have a role in the progression of NAFLD and its associated fibrosis, being a plausible determinant in the progression from steatosis to NASH.