Advanced Fibrosis Research Articles

Impact of Metabolic Syndrome Traits on Kidney Disease Risk in Individuals with MASLD: A UK Biobank Study.

The impact of metabolic syndrome (MetS) traits on chronic kidney disease (CKD) risk in metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. We investigated the impact of type and number of MetS traits and liver fibrosis on prevalent CKD and incident end-stage renal disease (ESRD) risk in SLD. 234 488 UK Biobank participants' were analysed. Hepatic steatosis index (> 36 for SLD, < 30 for no SLD) and MRI-proton density fat fraction (≥ 5.56%) were used to identify SLD. MetS traits were identified using MASLD criteria. Advanced fibrosis (FIB-4 score > 2.67) was determined using FIB-4 scores. eGFR < 60 mL/min/1.73 m2 or albuminuria > 3 mg/mmol identified prevalent CKD. A validated algorithm identified incident ESRD. Binary logistic and Cox regressions were used to test associations with prevalent CKD ([adjusted odds ratios (ORs)]) and incident ESRD (adjusted hazard ratios [HRs]) respectively. 102 410 participants (41.2%) had SLD. 64.4% had MetS. 1.3% had FIB-4 score > 2.67. With SLD and only one MetS trait, hypertension (OR 1.35, 95% CI 1.35-1.72) or type 2 diabetes (T2D) (OR 1.89, 95% CI 1.06-3.38) increased risk of prevalent CKD. MetS (≥ 3 traits) increased prevalent CKD risk (OR 1.94, 95% CI 1.75-2.15), which was further increased by advanced liver fibrosis (OR 4.29, 95% CI 3.36-5.47). CKD prevalence increased with increasing MetS traits. Over 13.6 years (median follow-up), MetS was associated with increased risk of developing ESRD (HR 1.70, 95% CI 1.19-2.43). In MASLD, hypertension, and T2D, number of MetS traits and liver fibrosis increased risk of prevalent CKD and presence of MetS increased the risk of incident ESRD.

NAFLD No More: A Review of Current Guidelines in the Diagnosis and Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Provide a concise update on metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as a practical approach to screening and initial evaluation. Nomenclature changes have placed a greater focus on cardiometabolic risk factors in the definition of MASLD. Screening for MASLD is by stepwise noninvasive serum and imaging tests which can identify patients at risk for advanced fibrosis and liver-related complications. MASLD has been increasing in prevalence and disease burden but is underrecognized in primary care and endocrinology clinics. Multiple society guidelines, synthesized here, provide a framework for the initial approach in the diagnosis and evaluation of MASLD. Recent advances in pharmacologic treatment underline the importance of screening for patients who are at risk for advanced fibrosis as they are most likely to benefit from new drug classes, such as the liver-directed thyroid receptor agonist resmiterom.

Abstract 4138624: Looking Beyond Respirophasic Ventricular Interdependence: A Case Report of Constrictive Pericarditis Masquerading as Cirrhosis

Case Presentation: A 67-year-old man with recurrent pleural effusions and concern for cirrhosis was referred for liver transplant. Pleural fluid was transudative by Light’s criteria with a high total protein level of 3.5 g/dL, which made hepatic hydrothorax unlikely. Liver biopsy confirmed congestive hepatopathy without advanced fibrosis. Transthoracic echocardiogram showed left ventricular (LV) ejection fraction 55%, right ventricular (RV) systolic pressure 35 mmHg, normal mitral annular tissue doppler velocities, and early diastolic septal bounce. Right and left heart catheterization showed prominent X and Y descent, elevated and equalized diastolic pressures, but no respiratory discordance in the LV-RV pressure gradient. As etiology of these findings were unclear, he underwent aggressive diuresis and hemodialysis, but repeat right heart catheterization showed persistently elevated right and left filling pressures. Cardiac MRI had no evidence of myocardial or pericardial inflammation/edema but showed pericardial thickening (7.9 mm) and septal bounce. There was no inspiratory septal shift, but the large pleural effusion appeared to limit diaphragm excursion. Given lack of respirophasic ventricular interdependence and thickened pericardium on MRI, CT was ordered, showing pericardial calcifications. Diagnosis of constrictive pericarditis was made, and patient underwent complete pericardiectomy. Pathology confirmed calcified and thick pericardium without acute inflammation. Post-operatively, patient developed RV failure, but recovered with inotrope support and was discharged with improvement in congestive symptoms. Discussion: Constrictive pericarditis classically exhibits respirophasic ventricular interdependence, but large pleural effusions may decrease respiratory variation in intrathoracic pressures, blunting this response. Normal mitral annulus tissue doppler velocities and lack of infiltrative process on cardiac MRI made restrictive cardiomyopathy unlikely. In the absence of respirophasic changes on multimodality testing, constriction can be diagnosed with other supportive features such as diastolic septal bounce, rapid Y descent, diastolic pressure equalization, and pericardial thickening and calcifications.

Weight Loss After Sleeve Gastrectomy According to Metabolic Dysfunction-Associated Steatotic Liver Disease Stage in Patients with Obesity: A Liver Biopsy-Based Prospective Study

Background: The role of metabolic dysfunction-associated steatotic liver disease (MASLD) in sleeve gastrectomy (SG)-related outcomes remains uncertain. In this study, we aimed to assess the influence of preoperative biopsy-proven MASLD and its stages on weight loss after SG. Methods: One hundred sixty-three patients with obesity undergoing SG with concomitant intraoperative liver biopsy were followed up for 1 year. Fifty-eight participants were categorized as no MASLD, thirty-eight as metabolic dysfunction-associated steatotic liver (MASL), and sixty-seven as metabolic dysfunction-associated steatohepatitis (MASH). Percentage total weight loss (%TWL) and percentage excess weight loss (%EWL) 1 year after SG were calculated for the different groups. We also evaluated the association between preoperative MASLD (and its stages) and weight loss, after adjusting for potential confounders. Results: Significant differences among groups were detected in %EWL (p = 0.004, ANOVA test), but not in %TWL (p = 0.079). However, significant differences in %TWL were found when MASH and no MASH (i.e., participants with MASL and participants without MASLD) groups were compared (27.3 ± 9.9 vs. 30.7 ± 9, respectively, p = 0.025). In the linear regression model for predicting %EWL 1 year after SG, the presence of MASH was independently associated with a lower %EWL, after adjusting for age, sex, baseline body mass index (BMI), and baseline glycated hemoglobin (HbA1c) (Beta −7.1; 95% CI −13.6, −0.5; p = 0.035). The presence of MASLD, liver fibrosis, or advanced liver fibrosis (≥F2) was also associated with lower %EWL after SG in crude models, although they did not remain significant after adjusting for these confounders. The presence of MASH was inversely related to %TWL, although the association did not remain significant after adjustment (Beta −2.7; 95% CI −5.7, 0.2; p = 0.069). Conclusions: MASH may be independently associated with lower %EWL 1 year after SG in patients with obesity.

Sequential Diagnostic Approach Using FIB-4 and ELF for Predicting Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease

Background and Aims: Multiple non-invasive tests (NITs) for identifying advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are available, but, due to the limitations of single NITs, the American Association for the Study of Liver Disease (AASLD) guidelines suggest a two-step strategy, combining the Fibrosis-4 Index (FIB-4) score with the Enhanced Liver Fibrosis (ELF) test to improve diagnostic accuracy and minimize unnecessary liver biopsies. However, few real-world studies have used such a sequential approach. We here evaluated the diagnostic accuracy of the ELF test in patients with recently established metabolic dysfunction-associated steatotic liver disease (MASLD) and assessed the clinical utility of applying a two-step strategy, including the ELF test following the FIB-4 score assessment, in patients with MASLD. Methods: We enrolled 153 patients diagnosed with MASLD who underwent liver biopsy at the Dong-A University Hospital between June 2018 and August 2023. The degree of fibrosis was determined based on liver biopsy results. Various NITs were used, including the Aminotransferase-to-Platelet Ratio Index (APRI), FIB-4 score, NAFLD Fibrosis score (NFS) and ELF test. The diagnostic efficacy of these NITs was evaluated based on the area under the receiver operating characteristic curve (AUROC). Additionally, the performance of each test was further examined both when applied individually and in a two-step approach, where FIB-4 was used followed by ELF testing. Key metrics such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were used for this analysis. Results: Overall, 153 patients with MASLD (mean age: 46.62 years; 52.3% men; 28.1% with type 2 diabetes) were included. The performance of the NITs in identifying advanced fibrosis was as follows: the AUROC of the APRI, FIB-4, NFS, and ELF tests were 0.803 (95% confidence interval (CI), 0.713–0.863), 0.769 (95% CI, 0.694–0.833), 0.699 (95% CI, 0.528–0.796), and 0.829 (95% CI, 0.760–0.885), respectively. The combination of the FIB-4 score ≥ 1.30 and the ELF score ≥ 9.8 showed 67.86% sensitivity, 90.40% specificity, a PPV of 75.18%, an NPV of 86.78%, an accuracy of 83.64%, and an AUROC of 0.791 for predicting the diagnosis of advanced fibrosis. This approach excluded 28 patients (71.8%) from unnecessary liver biopsies. Conclusions: Our study demonstrated that ELF testing maintained diagnostic accuracy in assessing liver fibrosis in patients with MASLD in real-world practice. This test was used as a second step in the evaluation, reducing clinically unnecessary invasive liver biopsies and referrals to tertiary institutions. This approach allows assessment of MASLD severity in primary care settings without requiring additional equipment.

Modified FIB-4 Index in Type 2 Diabetes Mellitus with Steatosis: A Non-Linear Predictive Model for Advanced Hepatic Fibrosis

Background: The Fibrosis-4 (FIB-4) index is widely recommended as a first-tier method for screening advanced hepatic fibrosis; however, its diagnostic performance is known to be suboptimal in patients with Type 2 diabetes mellitus (T2DM). We aim to propose a modified FIB-4, using the parameters of the existing FIB-4, tailored specifically for diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A total of 1503 patients who underwent liver biopsy were divided into T2DM (n = 517) and non-T2DM (n = 986) groups. The model was developed using multiple regression analysis in the derivation cohort and validated in the validation cohort. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic (AUC) curves. Results: Among the 1503 individuals, those with T2DM were older, more likely to be male, and had a higher prevalence of advanced hepatic fibrosis (≥F3) compared to non-T2DM individuals. Independent risk factors for advanced fibrosis in T2DM included age, AST, AST/ALT ratio, albumin, triglycerides, and platelet count. The optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index) demonstrated superior diagnostic accuracy (AUC 0.771) compared to the FIB-4 (AUC 0.735, p = 0.012). The model showed a higher negative predictive value than the original FIB-4 across all age groups in the diabetic group. Conclusions: The newly optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index), incorporating a non-linear predictive model, improves diagnostic performance (AUC) and the negative predictive value in MASLD with T2DM.

Magnetic resonance elastography is useful to determine the severity of liver fibrosis according to liver biopsy in post-fontan patients.

The reliability of various modalities for assessing and monitoring Fontan-associated liver disease compared to liver biopsy remains an intriguing subject of inquiry. Our objective was to assess the efficacy of multiple modalities in comparison to liver histology for evaluating liver fibrosis in post-Fontan patients. We conducted a cross-sectional study involving Fontan patients without known liver disease. Eligible patients underwent cardiac and hepatic evaluations, including ultrasound liver elastography, magnetic resonance elastography (MRE) of the liver, computerized tomography (CT) scan of the upper abdomen, echocardiography, cardiac catheterization, and liver biopsy. The severity of liver fibrosis was categorized using the METAVIR score derived from liver biopsy results: F0/F1 indicated no or mild fibrosis, F2 indicated significant fibrosis, F3 indicated advanced fibrosis and F4 indicated cirrhosis. A total of 38 patients (mean age 21 ± 6.5 years, 52.6% female) were included in the cross-sectional study, with a mean time elapsed since the Fontan operation of 13 years. Parameters obtained from echocardiography, ultrasound liver elastography, and CT scan of the upper abdomen did not exhibit significant differences among the groups. Notably, liver biopsy revealed advanced cirrhosis in 23 out of 38 patients and none were diagnosed with hepatocellular carcinoma. Multivariate logistic regression analysis demonstrated that the factor significantly associated with significant liver fibrosis or cirrhosis in post-Fontan patients was liver stiffness with MRE > 4.4kPa [OR 13.5 (95% CI 1.2-152.2)]. Our findings suggest that post-Fontan patients with liver stiffness of MRE > 4.4kPa should undergo further investigation. These results contribute to understanding the liver fibrosis assessment in post-Fontan patients and highlight the importance of MRE in predicting significant liver disease.

Association of dietary inflammatory index with sarcopenia in patients with Metabolic dysfunction-associated fatty liver disease: a cross-sectional study

BackgroundSarcopenia is a common complication of fatty liver, and sarcopenia increases the risk of advanced liver fibrosis in patients with Metabolic dysfunction-associated fatty liver disease (MAFLD). Chronic inflammation is the crucial link between sarcopenia and fatty liver. An anti-inflammatory diet is expected to be an essential measure to prevent sarcopenia in patients with fatty liver, and the dietary inflammatory index (DII) is a crucial tool for assessing the inflammatory potential of diets. However, the relationship between DII and sarcopenia in patients with fatty liver is unclear.ObjectiveThis study investigated the correlation between the dietary inflammatory index (DII) and sarcopenia in patients with Metabolic dysfunction-associated fatty liver disease (MAFLD).MethodsData for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2017–2018, with 917 patients with MAFLD participating in the study. Participants were divided into three groups based on DII tertiles: group T1 (n = 305), group T2 (n = 306), and group T3 (n = 306), and binary logistic regression was used to assess the relationship between DII and sarcopenia with stratified analyses based on the weights recommended by the NHANES and multivariate linear regression was used to evaluate the association of DII with total appendicular lean mass.ResultsAfter adjusting for all confounders, DII was significantly and positively associated with the risk of sarcopenia in women [OR: 1.61, 95% CI: (1.226, 2.06), p &amp;lt; 0.001]. The risk of sarcopenia was higher in the T3 group compared to the T1 group [OR: 4.04, 95% CI: (1.66, 9.84), p = 0.002]. DII was negatively associated with appendicular lean mass adjusted for body mass index in both men and women.ConclusionDII was significantly associated with the risk of sarcopenia in female patients with MAFLD, with higher DII scores related to a higher risk of sarcopenia. Higher DII scores related to a higher risk of sarcopenia in men with significant fibrosis.

Association Between Noninvasive Liver Fibrosis Scores and Heart Failure in a General Population.

The association between nonalcoholic fatty liver disease and cardiovascular disease is firmly established, yet the association between noninvasive liver fibrosis scores and cardiovascular events remains a topic of uncertainty. Our study aimed to explore the association between liver fibrosis and heart failure. The data set was from the National Health and Nutrition Examination Survey 2011 to 2018. Advanced hepatic fibrosis risk was assessed through 3 noninvasive liver fibrosis scores: Fibrosis-4 score (FIB-4), the nonalcoholic fatty liver disease fibrosis score (NFS), and the aspartate aminotransferase to platelet ratio index (APRI). We included 19 695 eligible participants. The national prevalence of advanced liver fibrosis risk in the United States was 4.20%, 8.06%, and 0.35% as determined by FIB-4, NFS, and APRI scores, respectively. Weighted logistic regression analysis revealed significant associations between advanced liver fibrosis risk and the prevalence of heart failure (continuous variables, FIB-4: odds ratio [OR], 1.15 [95% CI, 1.07-1.23]; NFS: OR, 1.42 [95% CI, 1.23-1.64]; APRI: OR, 1.44 [95% CI, 1.15-1.81]). When the scores were assessed as categorical variables, the results were still significant (FIB-4 ≥2.67 versus FIB-4 <1.3: OR, 2.18 [95% CI, 1.47-3.24]; NFS ≥0.675 versus NFS <-1.455: OR, 2.53 [95% CI, 1.37-4.68]). Subgroup analysis found that the association between APRI and heart failure was stronger in female patients. In the general US population, the prevalence of advanced liver fibrosis risk varied between 0.35% and 8.06% as indicated by noninvasive liver fibrosis scores. FIB-4, NFS, and APRI scores were linked to an elevated prevalence of heart failure.

An Assessment of the Feasibility, Patient Acceptance, and Performance of Point-of-Care Transient Elastography for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review and Meta-Analysis

Background: Vibration-Controlled Transient Elastography (VCTE) with FibroScan is a non-invasive, reliable diagnostic tool for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD), enabling early detection and management to prevent severe liver diseases. VCTE’s ease and portability suit primary care, streamlining referrals, promoting lifestyle changes, reducing costs, and benefiting underserved communities. Methods: Studies on point-of-care VCTE were systematically reviewed, followed by meta-analysis using a random-effects model. Pooled proportions with 95% confidence intervals were reported, and heterogeneity was assessed using I2%. Results: A total of twenty studies from 14 countries, including 6159 patients, were analyzed, with three studies from France, two from the U.S., and four from China. The population had a slight male preponderance, with a mean age range of 35–73 years and a BMI range of 24.4–41.1%. The diagnostic accuracy for detecting any fibrosis (≥F1) was reported in four studies (n = 210) with an AUC of 0.74, sensitivity of 69.5%, and specificity of 70.6%. For significant fibrosis (≥F2), eight studies (n = 650) reported an AUC of 0.69, sensitivity of 81.7%, and specificity of 64.6%. Advanced fibrosis (≥F3) was evaluated in 10 studies (n = 619), with an AUC of 0.84, sensitivity of 88.1%, and specificity of 63.8%. Cirrhosis (F4) was assessed in nine studies (n = 533), with an AUC of 0.65, sensitivity of 87.5%, and specificity of 62.6%. Steatosis diagnoses across stages S1 to S3 showed increasing diagnostic accuracies, with AUCs of 0.85, 0.76, and 0.80, respectively. Probe type and BMI were significant covariates influencing diagnostic performance for both fibrosis and steatosis, while the percentage of male participants also showed significant associations. Conclusions: VCTE shows high diagnostic accuracy for fibrosis and steatosis in MASLD patients at the point of care. Future research should assess its implementation in fibroscan settings.

Regression of hepatic fibrosis after pharmacological therapy for nonalcoholic steatohepatitis.

The global incidence of nonalcoholic fatty liver disease (NAFLD) is escalating considerably. NAFLD covers a range of liver conditions from simple steatosis to the more severe form known as nonalcoholic steatohepatitis, which involves chronic liver inflammation and the transformation of hepatic stellate cells into myofibroblasts that generate excess extracellular matrix, leading to fibrosis. Hepatocyte ballooning is a key catalyst for fibrosis progression, potentially advancing to cirrhosis and its decompensated state. Fibrosis is a critical prognostic factor for outcomes in patients with NAFLD; therefore, those with substantial fibrosis require timely intervention. Although liver biopsy is the most reliable method for fibrosis detection, it is associated with certain risks and limitations, particularly in routine screening. Consequently, various noninvasive diagnostic techniques have been introduced. This review examines the increasing prevalence of NAFLD, evaluates the noninvasive diagnostic techniques for fibrosis, and assesses their efficacy in staging the disease. In addition, it critically appraises current and emerging antifibrotic therapies, focusing on their mechanisms, efficacy, and potential in reversing fibrosis. This review underscores the urgent need for effective therapeutic strategies, given the dire consequences of advanced fibrosis.

Metabolic and hepatic phenotypes in sarcopenic obesity and impact of bariatric surgery

Background & AimsSarcopenic obesity (SO) is associated with cardiometabolic disorders and steatotic liver disease and carries major health risks. We assessed the hepatic and metabolic clinical phenotype associated with SO in patients with obesity undergoing bariatric surgery (BS). We also evaluated whether weight-loss and metabolic improvement post-surgery differ between patients with and without SO. Methods972 consecutive patients from a single-center BS cohort who underwent whole-body dual-energy X-ray absorptiometry (DXA) and peri-operative liver biopsy were included. SO was diagnosed using the AIM-SO score, an AI-assisted unbiased clustering algorithm based on body composition. One-year post-surgery, 862 patients were reassessed for AIM-SO score changes. ResultsPre-operatively, 207 (21.3%) patients were diagnosed with SO. These patients had significantly higher prevalence of type-2 diabetes (T2D), arterial hypertension and obstructive sleep apnea (OSA) compared to patients without SO (all p≤0.003). Patients with SO had more severe liver damage: higher grades of moderate/advanced steatosis (64.2% vs. 47.3%), steatohepatitis (44.4% vs. 32.3%) and advanced fibrosis (12.1% vs. 6.0%) (all p≤0.01). One-year post-BS, 58.5% of patients had remission of SO. Patients with persistent SO exhibited less weight-loss than those with SO remission (–23.8 kg vs. –29.1 kg, p<0.001) and had lower rates of remission for T2D (41.9% vs. 69.8%), arterial hypertension (20.8% vs. 45.3%), and metabolic syndrome (47.6% vs. 75.0%) (all p≤0.009). ConclusionThe DXA-based AIM-SO score identifies patients with SO who are at greater risk of hepatic and cardiometabolic comorbidities, and predicts less favorable weight-loss and metabolic improvements post-BS.

Liver transcriptome analysis reveals PSC-attributed gene set associated with fibrosis progression

BackgroundPrimary Sclerosing Cholangitis (PSC) is a chronic heterogenous cholangiopathy with unknown etiology where chronic inflammation of the bile ducts leads to multifocal biliary strictures and biliary fibrosis with consecutive cirrhosis development. We here aimed to identify a PSC-specific gene signature associated with biliary fibrosis development. MethodsWe performed RNA-sequencing of 47 liver biopsies from people with PSC (n = 16), primary biliary cholangitis (PBC, n = 15), and metabolic dysfunction-associated steatotic liver disease (MASLD, n = 16) with different fibrosis stages to identify a PSC-specific gene signature associated with biliary fibrosis progression. For validation, we compared an external transcriptome data set of liver biopsies from people with PSC (n = 73) with different fibrosis stages (DOI: 10.1002/hep.31488; baseline samples from NCT01672853). ResultsDifferential gene expression analysis of the liver transcriptome from PSC patients with advanced versus early fibrosis revealed 431 genes associated with fibrosis development. Of those, 367 were identified as PSC-associated when compared to PBC or MASLD. Validation against an external data set of 73 liver biopsies from PSC patients with different fibrosis stages led to a condensed set of 150 (out of 367) DEGs. Cell type specificity assignment of those genes by using published single cell RNA-seq data revealed genetic disease drivers expressed by cholangiocytes (e.g. CXCL1, SPP1), fibroblasts, innate and adaptive immune cells while deconvolution along fibrosis progression of the PSC, PBC, MASLD samples highlighted an early involvement of macrophage- and neutrophil-associated genes in PSC fibrosis. ConclusionWe reveal a PSC-attributed gene signature associated with biliary fibrosis development that may enable the identification of potential new biomarkers and therapeutic targets in PSC-related fibrogenesis. IMPACT AND IMPLICATIONSPrimary sclerosing cholangitis (PSC) is an inflammatory liver disease that is characterized by multifocal inflammation of bile ducts and subsequent biliary fibrosis. Herein, we identify a PSC-specific gene set of biliary fibrosis progression attributing to a uniquely complex milieu of different cell types, including innate and adaptive immune cells while neutrophils and macrophages showed an earlier involvement in fibrosis initiation in PSC in contrast to PBC and MASLD. Thus, our unbiased approach lays an important groundwork for further mechanistic studies for research into PSC-specific fibrosis.

Assessment and integration of multiparametric MRI for liver fibrosis staging in rat non-alcoholic steatohepatitis: Evaluation of diagnostic efficiency and model interpretation

ObjectivesMulti-parametric MRI techniques, including intravoxel incoherence motion (IVIM), iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL IQ), T2* mapping and T2 mapping, were employed to develop and validate a predictive model for non-alcoholic steatohepatitis (NASH) diagnosis and liver fibrosis (LF) staging in rats. The combined model was interpreted using SHapley Additive exPlanations (SHAP) values for model understanding. Materials and methods160 healthy Sprague-Dawley (SD) rats were divided into control (n = 24) and experimental (n = 136) groups, and the 12-week and 16-week groups were injected intraperitoneally with carbon tetrachloride (CCl4) for 4 weeks, one month before the final feeding period. All rats were subjected to pathological examination to determine LF stage. Upon the study’s completion, 147 SD rats were assessed for liver fibrosis. Results84 SD rats were diagnosed with NASH and 31, 10, and 43 rats were histologically diagnosed with no fibrosis (F0), early LF (F1-F2), and late LF (F3-F4). For diagnosis of NASH and staging of liver fibrosis associated with NASH, a combined multi-parameter magnetic resonance imaging prediction model has a higher area under the ROC curve (AUC) than individual diffusion parameters, especially in advanced stages of fibrosis, with an AUC of 0.929 for the combined model. In SHAP, the free fluid(FF) value contributes most to the model for diagnosing NASH and advanced liver fibrosis, while the T2 value contributes most for diagnosing liver fibrosis and the apparent diffusion coefficient (ADC) value contributes most for diagnosing liver cirrhosis. ConclusionsThe integration of several magnetic resonance imaging methods along with SHAP value analysis provides a more comprehensive and theoretical investigation into the mechanisms and factors contributing to the progression of liver fibrosis in NASH, offering insights from various angles.

Development of fully automated models for staging liver fibrosis using non-contrast MRI and artificial intelligence: a retrospective multicenter study

Accurate staging of liver fibrosis (LF) is essential for clinical management in chronic liver disease. While non-contrast MRI (NC-MRI) yields valuable information for liver assessment, its effectiveness in predicting LF remains underexplored. This study aimed to develop and validate artificial intelligence (AI)-powered models utilizing NC-MRI for staging LF. A total of 1726 patients from Shengjing Hospital of China Medical University, registered between October 2003 and October 2022, were retrospectively collected, and divided into development (n=1208) and internal test (n=518) cohorts. An external test cohort consisting of 337 individuals from six centers, registered between June 2015 and November 2022, were also included. All participants underwent NC-MRI (T1-weighted imaging, T1WI; and T2-fat-suppressed imaging, T2FS) and liver biopsies. Two classification models (CMs), named T1 and T2FS, were trained on respective image types using 3D contextual transformer networks and evaluated on both test cohorts. Additionally, three CMs-Clinic, Image, and Fusion-were developed using clinical features, T1 and T2FS scores, and their integration via logistic regression. Classification effectiveness of CMs was assessed using the area under the receiver operating characteristic curve (AUC). A comparison was conducted between the optimal models (OMs) with highest AUC and other methods (transient elastography, five serum biomarkers, and six radiologists). Fusion models (i.e., OM) yielded the highest AUC among the CMs, achieving AUCs of 0.810 for significant fibrosis, 0.881 for advanced fibrosis, and 0.918 for cirrhosis in the internal test cohort, and 0.808, 0.868, and 0.925, respectively, in the external test cohort. The OMs demonstrated superior performance in AUC, significantly surpassing transient elastography (only for staging≥F2 and ≥ F3 grades), serum biomarkers, and three junior radiologists for staging LF. Radiologists, with the aid of the OMs, can achieve a higher AUC in LF assessment. AI-powered models utilizing NC-MRI, including T1WI and T2FS, accurately stage LF. National Natural Science Foundation of China (No. 82071885); General Program of the Liaoning Provincial Department of Education (LJKMZ20221160); Liaoning Province Science and Technology Joint Plan (2023JH2/101700127); the Leading Young Talent Program of Xingliao Yingcai in Liaoning Province (XLYC2203037).

Uncommon granulomatous manifestation in Epstein-Barr virus-positive follicular dendritic cell sarcoma: a case report.

Hepatic Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) represents a rare form of liver malignancy. The absence of distinct clinical and radiological characteristics, compounded by its rare occurrence, contributes to a challenging diagnosis. Here, we report a case of a 54-year-old Chinese female with a background of chronic hepatitis B virus treated with entecavir and complicated by advanced fibrosis presenting with a liver mass found on her annual surveillance ultrasound. Hepatectomy was performed under clinical suspicion of hepatocellular carcinoma. Immunomorphologic characteristics of the tumor were consistent with EBV+ IFDCS with distinct non-caseating granulomatous inflammation. Our case illustrates the importance of considering EBV+ IFDCS in the differential diagnosis of hepatic inflammatory lesions. Awareness of this entity and its characteristic features is essential for accurately diagnosing and managing this rare neoplasm.

Is Schistosoma mansoni playing a part in liver carcinogenesis?

The relationship between Schistosoma mansoni (Sm) and hepatocellular carcinoma (HCC) has been evaluated by many studies that point towards a co-relation between schistosomal infection and HCC. While many such studies demonstrated that Sm infection in the presence of another carcinogenic factors leads to HCC, none of these studies could conclusively prove the cancer-inducing ability of Sm in humans, independent of other carcinogenic factors. The aim of this work is to present the current understanding on the association of Sm with HCC. Many epidemiological, pathological, and clinical studies have shown the role of multiple events like chronic inflammation and fibrosis as well as hepato-toxic agents like soluble egg antigens (SEAs), which help in creating a micro-environment which is suitable for HCC development. The role of Sm infection and deposited eggs in causing persistent inflammation, advanced fibrosis, and the role of SEAs, especially IPSE/alpha-1, is emphasised. This work concludes that Sm infection has the potential to induce cancer independently but the same has not been reported in humans to date. Extensive research is required to establish a causal relationship between Sm infection and HCC induction, or a complete lack thereof. However, Sm infection definitely acts along with other carcinogenic factors to induce HCC at a much faster pace and also leads to an aggressive form of liver cancer, which the other carcinogenic factor could not have achieved alone.

Disparities in steatosis prevalence in the United States by Race or Ethnicity according to the 2023 criteria

IntroductionThe 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature.MethodsWe undertook a cross-sectional study employing the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed.ResultsA total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1–43.8%), MetALD 1.7% (95% CI: 1.3–2.0%), and ALD 0.6% (95% CI: 0.3–0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40–64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk.ConclusionsMASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated.

Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study.

Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5years after successful HCV treatment) in persons with HIV/HCV coinfection. We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index. During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG. We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.

An Elevated FIB-4 Score is associated with the severity of heart failure

Abstract Background Liver disease and heart failure (HF) are known to be closely associated. Non-invasive tests (NIT), such as the FIB-4 score, have been recommended by different guidelines to rule out advanced liver fibrosis and to stratify the risk of liver-related outcomes in patients with chronic liver diseases. Purpose Thus, our goal was to evaluate the connection between the FIB-4 index, heart failure, associated comorbidities, and cardiological biomarkers that predict the risk of liver fibrosis in patients with heart failure. Methods HF patients hospitalized in the cardiology department were divided into a group with an FIB-4 index &amp;lt;1.3 (indicating a low risk of liver fibrosis) (n=53) and a group with an FIB-4 index ≥1.3 (indicating intermediate and high risk of fibrosis) (n=59). Clinical examinations, laboratory results, echocardiography with Vivid E95-GE Healthcare, non-invasive body mass analysis with Body Composition Analyzer (Tanita Pro), and measurements of NT-proBNP, growth differentiation factor 15 (GDF-15), galectin-3, fatty acid-binding protein (FABP), copeptin, and vascular endothelial growth factor (VEGF) concentrations were performed. Results The patients with an FIB-4 index ≥1.3 had significantly higher: left ventricular volume index (LAVI) (p=0.004), E/E’ ratio (p=0.004) and lower left ventricular ejection fraction (p=0.003) compared to group with low risk of liver fibrosis. There were no differences in body mass compartments between groups except for ECW/TBW (%) - an index of body water distribution, which was lower in low-risk liver fibrosis group (p=0.0002). Patients with an FIB-4 index ≥1.3 had also lower: GFR MDRD (median 59.95 vs 85.1 mL/min/1.73 m²; p&amp;lt;0.001), total cholesterol (116.5 vs 15 mg/dL; p=0.002), LDL cholesterol (median 56 vs 93 mg/dL; p&amp;lt;0.0001) and HDL cholesterol (median 39 vs 47 mg/dL; p=0.03). Regarding heart failure biochemical biomarkers, patients with low risk of liver fibrosis had significantly lower level of NT-proBNP (median 37 vs 161 pg/ml; p&amp;lt;0.0001), GDF-15 (median 399.6 vs 898.9 pg/ml; p&amp;lt;0.0001) and FABP (median 101 vs 264,7 pg/ml; p=0.04). In a multiple logistic regression model the factors that were independently associated with the risk of liver fibrosis in HF patients based on an FIB-4 index were GDF-15 &amp;gt;724 pg/ml (OR 33.7, 95%CI: 6.5-174.2; p=0.0001), and NT-proBNP &amp;gt;129 pg/ml (OR 19.9, 95% CI: 3.8-103; p=0.0001) (Figure 1) Conclusion Our study suggests association between an elevated FIB-4 score and heart functions, and kidney impairment with fluid overload but not with higher total and low density cholesterols fractions or percentage of fat. Higher GDF-15 and NT-proBNP levels are independently associated with the risk of liver fibrosis based on an FIB-4 index. FIB-4 index in HF patients is an easy method to monitor the risk of liver fibrosis and might help to predict the HF progression and CVD complications.