Non-invasive Fibrosis Markers Research Articles

Non-invasive markers of hepatic steatosis and fibrosis following INSTI initiation in women with HIV.

The impact of integrase strand-transfer inhibitors (INSTIs) on steatotic liver disease in women with HIV (WWH) is unknown. Using data collected in the Women's Interagency HIV Study from 2007-2020, change in Fibrosis-4 index (FIB4), aspartate aminotransferase to platelet ratio index (APRI), and non-alcoholic fatty liver disease fibrosis score (NFS) over 5 years was compared between virologically-suppressed WWH who switched to or added an INSTI to their antiretroviral therapy (ART) and WWH remaining on non-INSTI ART. In participants with transient elastography (TE) measures, estimates of hepatic steatosis (controlled attenuation parameter, CAP), fibrosis (liver stiffness, LS), and steatohepatitis (FibroScan-aspartate aminotransferase scores, FAST) were compared by group. A total of 872 WWH (323 INSTI, 549 non-INSTI) were included, and 280 (146 INSTI, 134 non-INSTI) had TE. Of these, 61% were Non-Hispanic Black; mean age was 47 years and body mass index was 31.4 kg/m2. Among non-obese women, those in the INSTI compared to the non-INSTI group had a greater increase in NFS (but not FIB4 or APRI) over time (study group*time, p=0.015). Those in the INSTI compared to non-INSTI group also had greater CAP (+25, 95%CI:0.28-49, p=0.048), LS (+1.23, 1.01-1.49, p=0.038), and FAST scores (+1.97, 1.17-3.31, p=0.011) and a 3.7 (1.2-11.4, p=0.021) greater odds of having hepatic steatosis (CAP≥248 dB/m) within 1 year of starting an INSTI. Hepatic steatosis risk was increased only within the first year following INSTI initiation among WWH. Longitudinal hepatic assessments are warranted to evaluate whether these changes are associated with clinically significant liver disease.

Comparative application of MAFLD and MASLD diagnostic criteria on NAFLD patients: insights from a single-center cohort

The diagnostic criteria for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) and Metabolic Associated Steatotic Liver Disease (MASLD) aim to refine the classification of fatty liver diseases previously grouped under Non-Alcoholic Fatty Liver Disease (NAFLD). This study evaluates the applicability of the MAFLD and MASLD frameworks in NAFLD patients, exploring their clinical utility in identifying high-risk patients. A total of 369 NAFLD patients were assessed using MAFLD and MASLD diagnostic criteria. Baseline characteristics, metabolic profiles, hepatic fibrosis, and cardiovascular risks were compared across the groups. Among NAFLD patients, 97.55% (n = 359) met MASLD criteria, and 97.01% (n = 357) fulfilled MAFLD criteria. Both frameworks MAFLD and MASLD captured overlapping populations, with MASLD encompassing slightly more cases. No significant differences were observed in metabolic risk factors, fibrosis indices (APRI, FIB-4, NAFLD fibrosis score), or cardiovascular risk (10-year ASCVD score). A small subset of lean NAFLD patients (10 cases) with distinct profiles remained uncategorized by either framework. Pure NAFLD cases (n = 10) were with mild insulin resistance (HOMA-IR: 3.07 ± 0.33) and slightly elevated LDL (102.5 ± 42.87 mg/dL), while fibrosis indices indicated low fibrosis risk. Steatosis indices supported the diagnosis of early-stage NAFLD with preserved liver function. These patients do not meet the criteria for inclusion in the MAFLD or MASLD frameworks, highlighting a gap in the current diagnostic systems. MAFLD and MASLD criteria align closely with NAFLD in capturing patients with metabolic risk with MASLD-enhanced inclusivity. Further refinement is required to address heterogeneity, particularly in lean NAFLD patients. Hypertension prevalence was comparable (17.4% in NAFLD, 18.2% in MAFLD, 17.8% in MASLD; p = 0.960), as was diabetes mellitus (36.7%, 37.8%, and 37.6%, respectively; p = 0.945). Body mass index was also similar across groups, with medians of 33.25, 33.6, and 33.4 kg/m2 (p = 0.731). Non-invasive markers of hepatic fibrosis, including APRI, FIB-4, and NAFLD fibrosis scores, did not differ significantly, with median FIB-4 scores around 1.05 (p = 0.953). Similarly, were the results of hepatic steatosis index and ASCVD score.

Endoscopic Ultrasound Guided Portosystemic Pressure Gradient Correlates with Clinical Parameters and Liver Histology.

Endoscopic ultrasound guided portosystemic pressure gradient measurement (EUS-PPG) is a novel technique to evaluate for portal hypertension (PH), a diagnosis that can prognosticate and guide therapy for patients. This study evaluated the safety and efficacy of EUS-PPG and correlation with clinical parameters and liver histology. We conducted a multi-center, retrospective study of patients undergoing EUS-PPG from January 2020 to December 2022 for suspected liver disease or PH. Linear regression was used to examine the relationship between EUS-PPG and clinical parameters of PH and the chi square test, Fisher's exact test, and Wilcoxon Rank Sums test described correlation with liver biopsy histology and non-invasive markers of fibrosis (FIB-4, APRI). Logistic regression was performed to identify the strongest predictor of histologic cirrhosis. Across 8 centers, 385 patients were enrolled and 373 had successful EUS-PPG (technical success 97%). Higher median PPGs were observed in patients with than without esophageal varices (11.6mmHg vs 4.1), portal hypertensive gastropathy (10.5mmHg vs 3.3), and thrombocytopenia (7.6 mmHg vs 4.4) (p<0.001). Individuals with PH and clinically significant PH (PPG>10) were 6.7 and 3.8 times more likely to have cirrhosis on histology. EUS-PPG was the best overall predictor of biopsy proven cirrhosis (AUC 0.84) compared to FIB-4 (0.72), and APRI (0.54). There were 2 minor adverse events related to PPG (post procedural pain). EUS-PPG measurement was technically feasible, safe and demonstrated strong correlation with clinical parameters of PH and liver histology. The strongest predictor of cirrhosis was EUS-PPG >5mm Hg which outperformed non-invasive markers of fibrosis.

Phenotypes of primary sclerosing cholangitis in children

Background. Primary sclerosing cholangitis (PSC) in children is a rare chronic immune-mediated disease of the biliary tract, which, unlike in adults, has a less aggressive course with da­mage to the intrahepatic bile ducts and is combined with autoimmune hepatitis, creating a special clinical phenotype of PSC, autoimmune sclerosing cholangitis (ASC). Although immunosuppressive therapy is effective in controlling autoimmune inflammation, it does not inhibit the progression of fibrotic changes around the bile ducts, which, unfortunately, leads to the formation of biliary cirrhosis of the liver. Research aimed at studying the clinical course of PSC in children and improving early diagnosis is relevant, especially given the limited access to modern diagnostic methods, such as magnetic resonance cholangiopancreatography, the need for invasive studies, and the lack of standardized diagnostic criteria adapted to childhood, which complicates the diagnosis and treatment of these patients. Objective: to investigate the clinical features of primary sclerosing cholangitis in children and adolescents depending on di­sease phenotype with the aim of develo­ping individualized treatment approaches. Materials and methods. Retrospective and prospective analysis of the clinical course of primary sclerosing cholangitis in children and adolescents who were treated and followed at the Department of Pediatric Hepatology from 2016 to 2024 was conducted. The study included 68 children (62 % boys and 38 % girls) with PSC aged 3 to 18 years (mean age at diagnosis was (11.0 ± 3.9) years). Of these, 38 patients (56 %) had autoimmune sclerosing cholangitis, and 30 (44 %) had isolated PSC without clinical or histological signs of autoimmune hepatitis. Results. At disease onset, 40 % of children with PSC had liver fibrosis graded F3-F4 on METAVIR, with 24 % showing cirrhosis. The most common phenotype in children with PSC was a mixed one involving both large and small bile ducts (63 %). PSC with large bile duct involvement alone was observed in 11 % of cases, 70 % of these children were diagnosed with cirrhosis. Small duct involvement alone was present in 26 % of cases, with cirrhosis in 12.5 % (p = 0.01). Inflammatory bowel disease (IBD) was diagnosed in 84 % of children with PSC: 32 % had ulcerative colitis, 38 % had indeterminate IBD, and 16 % had Crohn’s disease. Pancolitis occurred in 56 % of cases, while 19 % of patients had histological signs of IBD without clinical or endoscopic manifestations. Asymptomatic IBD was diagnosed in 58 % of cases. The clinical course of ASC differed from isolated PSC with significantly higher rates of anemia (47 vs. 27 %, p = 0.03), elevated serum IgG levels (23.9 vs. 12.5 g/l, р &lt; 0.01), and higher levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin (p &lt; 0.01 for all), non-invasive fibrosis markers (APRI, FIB-4, 2D-SWE) at onset (p &lt; 0.01; p = 0.01; p = 0.04, respectively). Liver fibrosis F3-F4 on METAVIR was more frequently diagnosed in ASC group than in patients with isolated PSC (73 vs. 40 %, p = 0.06). Large bile duct involvement alone was found only in isolated PSC (p &lt; 0.0009). No differences were observed between ASC and isolated PSC in terms of IBD phenotype. Conclusions. PSC in children is represented by 2 phenotypes (ASC and isolated PSC) that occur with almost equal frequency. ASC and isolated PSC have similar phenotypes of biliary and intestinal lesions, however, they differ in terms of clinical course and therapeutic approaches. Involvement of the large bile duct alone in children with PSC is associated with rapid formation of liver fibrosis and cirrhosis. PSC phenotype with involvement of small bile ducts alone has a favorable course in children. Most children with PSC exhibit the PSC-IBD phenotype. Active diagnostic search for biliary and intestinal lesions in children with PSC will facilitate the development of effective personalized approaches to treatment and monitoring, thereby improving disease prognosis.

Integration of Non-invasive Screening for Cystic Fibrosis Related Liver Disease in the Regular Follow-Up for Cystic Fibrosis.

The reported prevalence of cystic fibrosis (CF)-related liver disease (CFLD) reaches up to 40% in some cohorts. CFLD is the 3rd leading cause of mortality among patients with CF. The aims of this study were to evaluate the prevalence of CFLD in a cohort followed at a tertiary university center, to define the types of liver involvement, and to determine how non-invasive screening methods can be optimally integrated into clinical practice. The files of patients followed at the CF clinic of the Centre hospitalier de l'Université de Montréal (CHUM) between 2020 and 2022 were retrospectively reviewed. The NIH criteria were used to define CFLD through the presence of one major criterion (abnormal imaging) or two minor criteria (persistently abnormal laboratory values, hepatosplenomegaly, or transient elastography (TE) ≥ 7kPa). A total of 357 patients were included in this study. CFLD was observed in 46 patients (13%). Among these, major criteria led to diagnosis in 43 patients (with or without minor criteria). TE performed best in non-invasive assessment of CLFD (area under the curve (AUROC) 0.80 (0.68-0.92, p = 0.0007)). A nodular liver was detected in 27 patients (7%), and was associated with higher non-invasive markers of fibrosis. In addition, presence of a nodular liver was associated with significant short-term mortality (14.8% vs. 1.5%, p = 0.003). Early recognition of CFLD in clinical care can potentially prevent complications of cirrhosis and portal hypertension. The use of abdominal imaging and TE seems promising for detecting CFLD.

Aspartate aminotransferase-to-platelet ratio index outperforms Fibrosis-4 in 2843 Korean patients with metabolic dysfunction-associated steatotic liver disease.

The definition of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD. This retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration-controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and serum Mac-2-binding protein glycosylation isomer were analyzed. Among 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis≥F3, and 0.890, 0.884, and 0.889 for fibrosis≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB-4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis≥F2, 0.788, 0.814, and 0.79 for fibrosis≥F3, and 0.846, 0.859, and 0.856 for fibrosis≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64years for fibrosis≥F4. The APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age-stratified analyses. Further research is needed to establish standardized cut-off values and enhance the clinical utility of these markers in managing liver fibrosis.

Correlation of the FIB-4 Liver Biomarker Score with the Severity of Heart Failure.

Background and Objectives: Heart failure is associated with high morbidity and mortality and linked with several pre-existing health conditions and risk factors. Early detection and prompt management in heart failure improves patient outcomes. Liver involvement is associated with heart failure disease progression, and hence liver biomarkers and liver fibrosis may have a prognostic impact. Several blood test based markers and scoring systems estimate liver fibrosis and hence can be useful prognostic tools. Materials and Methods: We retrospectively analyzed a series of 303 patients with decompensated heart failure in a city in western Romania over a period of 6 months. Several biochemical parameters were measured, the FIB-4 score was estimated and echocardiography was performed. Results for targeted variables are presented using descriptive statistics. Patients were analyzed based on their LVEF categories. Statistical analysis was based on ANOVA one-way tests for continuous variables and Chi-square tests for categorical variables. Pairwise comparisons were performed based on Bonferroni adjusted significance tests. The correlations between FIB-4 score, LVEF and NT-pro BNP in patients with and without diabetes and hypertension were explored using Spearman's correlation coefficient. Result: Age, gender, NYHA class, death, history of (h/o) type 2 diabetes mellitus (T2DM), h/o coronary artery disease (CAD), h/o arrhythmias, sodium, potassium, creatinine, eGFR, uric acid, NT-pro BNP, left atrial volume, LDL, HDL, and TG were analyzed by LVEF categories using ANOVA one-way tests, Chi-square tests, and Bonferroni correction comparisons. We found a strong statistically significant correlation between each of NT-pro BNP, left atrial volume, LDL, and HDL with the LVEF categories. Discussion: Early detection of cardiac dysfunction leads to better management in patients with cardiovascular risk factors including diabetes and hypertension. High LDL and low HDL levels contribute to a reduction in left ventricular (LV) function. Available literature suggests the FIB-4 score as superior to other non-invasive markers of fibrosis. It utilizes the patient's age, platelet count, AST, and ALT, which can be available retrospectively, making it an easy and inexpensive tool. FIB-4 score has a few limitations. Conclusions: Our study has shown a statistically significant positive correlation between severity categories of LVEF and FIB-4 score for heart failure patients with and without diabetes, and for heart failure patients with or without hypertension. We propose the implementation of FIB-4 score as a prognostic tool for heart failure.

Role of Obeticholic Acid, a Farnesoid X Receptor Agonist, in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Background. Obeticholic acid (OCA) has emerged as a promising drug in the management of nonalcoholic fatty liver disease (NAFLD). This meta-analysis aimed to analyse the therapeutic effect of OCA on NAFLD. Methods. Randomized controlled trials (RCTs) involving patients with NAFLD receiving OCA in the intervention arm and placebo in the control arm were searched throughout the electronic databases. The primary outcomes were changes in non-invasive markers of hepatic fibrosis and liver histology. The secondary outcomes included changes in liver enzymes, metabolic parameters from baseline and adverse events (AEs). Results. Four RCTs involving 1,278 subjects met the inclusion criteria. Over 6 weeks to 18 months of clinical use, OCA outperformed placebo in resolving definite nonalcoholic steatohepatitis (odds ratio [OR] 1.60, 95% confidence interval [CI] [1.04-2.48], p=0.03) and improving fibrosis (OR 2.23, 95% CI [1.56-3.20], p<0.0001), hepatocellular ballooning (OR 1.83, 95% CI [1.35-2.47], p<0.0001) and lobular inflammation (OR 1.62, 95% CI [1.13-2.32], p=0.009). OCA did not improve the enhanced liver fibrosis score and steatosis better than placebo, and demonstrated superior efficacy compared with the placebo in reducing serum alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase levels. Although a favourable effect of OCA over placebo was seen in body-weight reduction, the OCA use was associated with adverse changes in lipid parameters. Except for the greater risk of pruritus and constipation, the AE profile was comparable between the OCA and placebo groups. Conclusions. OCA has a favourable efficacy in improving liver histology and liver enzymes. However, the worsening of lipid parameters and other AEs with the OCA use warrants further investigation.

Comparison of Non-invasive Biochemical Fibrosis Markers According to Obesity-Based Metabolic Profile in Chronic Liver Disease with Chronic Hepatitis B Etiology

Aim: The aim of this study is to investigate the impact of obesity on fibrosis by comparing fibrosis markers between obese and non-obese patients with Chronic Hepatitis B (CHB). Material and Method: A total of 172 CHB (50.6±9.4 mean aged) patients were included in this retrospective study. The patients were divided into two groups: Obese (n=72) and Non-obese (n=100). Inclusion criteria were those diagnosed with chronic hepatitis B and ≤ 50 IU/mL or undetectable HBV-DNA, and exclusion criteria were other chronic diseases other than CHB and pregnancy. The height, body weight, and waist circumferences were measured. BMI ≥30 kg/m2 was classified as the obese group. Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl transferase, albumin, bilirubin, and prothrombin time were analyzed. Fibrosis-4 score (FIB-4) was calculated with the formula Age x AST / platelet count x √(ALT), and AST-Platelet Ratio Index (APRI) was calculated with the formula [AST/AST (upper limit of normal)]/ platelet count. Results: AST levels were significantly higher in obese patients (p

A direct comparison of non-invasive blood markers of liver fibrosis as associates of cardiovascular risk. The Athens cardiometabolic registry

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). This risk increases further with advanced liver fibrosis. To date, non-invasive tests (NIT) for liver fibrosis risk have not been established as diagnostic or prognostic biomarkers of CVD. Purpose The purpose of the study was to compare NIT of liver fibrosis with respect to their associations with vascular injury and cardiovascular (CV) events. Methods Individuals without clinically overt CVD and patients with CVD (total n=1,692), consecutively recruited in the Athens Cardiometabolic Registry, were analysed in this study. We retrospectively evaluated the association of NIT (i.e. Fibrosis-4 index (FIB-4), NAFLD Fibrosis score (NFS), BARD score) with indices of subclinical arterial injury (i.e. carotid wall thickness and atherosclerotic plaque for subclinical atherosclerosis, pulse wave velocity (PWV), for arterial stiffness) and the incidence of CV events. Patients were followed-up for CV events for a median time of 39 months. Results Elevated FIB-4 (&amp;gt;2.67) was associated with vascular damage [adjusted odds ratio (aOR)=2.97, 95% confidence intervals (CI)= 1.71-5.78 for maximal wall thickness (maxWT) and aOR=4.58, 95% CI=2.44-8.60 for PWV] across the entire study population, including those with or without clinically overt CVD. NFS&amp;gt; 0.675 showed similar associations but lacked significant correlation with arterial stiffness in coronary artery disease patients. FIB-4&amp;gt; 2.67 and BARD&amp;gt; 2 were associated with increased risk of the composite endpoint of CV death, acute myocardial infarction, or coronary revascularization [adjusted hazard ratio, (aHR)=2.00, 95% CI= 1.12-3.55 and aHR=3.36, 95% CI=1.03-11.0 for FIB-4 (n=842) and BARD (n=887) respectively]. FIB-4 and BARD as continuous variables confered incremental prognostic value compared to European Systematic Coronary Risk Evaluation 2 (SCORE2). Conclusion In a population with a wide range of cardiometabolic risk, FIB-4 was associated with both markers of atherosclerotic disease and arterial stiffness as well as with adverse CV events. These data support further investigation of FIB-4 as a biomarker of CV risk.

Non-invasive fibrosis markers are useful in predicting the presence of varices in compensated cirrhosis and variceal bleeding in decompensated cirrhosis.

This study aims to investigate the effectiveness of non-invasive fibrosis markers in predicting varices in compensated advanced chronic liver disease patients and variceal bleeding in decompensated cirrhotic patients. Between 1 July 2020-2021, 137 newly diagnosed cirrhosis patients (67 females/70 males; mean age: 53.35) were included in the study. The diagnosis of cirrhosis was made based on clinical, laboratory, imaging, and, if available, biopsy findings. Laboratory and clinical parameters, including lysyl oxidase-like protein 2 (LOXL2), were recorded for all patients. Commonly used noninvasive fibrosis scores were calculated, and endoscopies were performed to assess varices. All patients were followed up for 12 months, and variceal bleeding events were recorded. Parameters that could predict the presence of varices and variceal bleeding were identified using appropriate statistical methods. Out of the 137 cirrhotic patients, 55 were in the compensated stage and 82 were in the decompensated stage. Varices were detected in 36 (65%) of the compensated cirrhotic patients. It was found that a variceal score derived from spleen size and the ELF score could be used to predict varices (AUC: 0.83). Variceal bleeding developed in 26 (31%) of the patients with decompensated cirrhosis. It was determined that a scoring system derived from albumin, spleen size, LOXL2 level, and the Lok index could be used to predict variceal bleeding in this patient group (AUC: 0.845). This study demonstrates that, besides device-dependent examinations, non-invasive fibrosis scores and various serum parameters can predict varices and variceal bleeding in cirrhotic patients.

Noninvasive evaluation of significant liver fibrosis in chronic hepatitis B patients.

Chronic hepatitis B is still a major cause of morbidity and mortality worldwide. In recent years, there has been increasing research on inexpensive, noninvasive, reproducible methods for detecting fibrosis in the liver. In this study, we examined the efficacy of 15 different noninvasive fibrosis markers for predicting significant liver fibrosis in chronic hepatitis B patients. Patients who underwent liver biopsy for chronic hepatitis B between 01.01.2010 and 01.01.2022 were retrospectively analysed. The study population was divided into two groups according to significant fibrosis (F≥3). Receiver operating characteristic analysis was performed to examine the diagnostic performance of these noninvasive fibrosis markers for the prediction of significant fibrosis. Multiple logistic regression analysis was used create a model which predicts significant fibrosis better than the individual markers. In total, 234 chronic hepatitis B patients were enrolled in this study. Among the 15 noninvasive fibrosis markers, King's score was found to have the biggest AUC in predicting significant fibrosis (F≥3). Furthermore, a model containing King's score, GUCI and GPR has the ability of prediction of significant fibrosis better than every individual marker (cut-off of the model >0,3356, p<0.0001). According to our study results, the model containing King's score, GUCI and GPR can be used to predict significant liver fibrosis in chronic hepatitis B patients followed-up in countries with limited sources.

Non-Invasive Serum Markers of Non-Alcoholic Fatty Liver Disease Fibrosis: Potential Tools for Detecting Patients with Cardiovascular Disease.

Non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases with a prevalence of 23%-25% globally, is an independent risk factor for cardiovascular diseases (CVDs). Growing evidence indicates that the development of NAFLD, ranging from non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), advanced fibrosis to cirrhosis, and even hepatocellular carcinoma, is at substantial risk for CVDs, which clinically contribute to increased cardiovascular morbidity and mortality. Non-invasive serum markers assessing liver fibrosis, such as fibrosis-4 (FIB-4) score, aspartate transaminase-to-platelet ratio index (APRI), and NAFLD fibrosis score (NFS), are expected to be useful tools for clinical management of patients with CVDs. This review aims to provide an overview of the evidence for the relationship between the progression of NAFLD and CVDs and the clinical application of non-invasive markers of liver fibrosis in managing patients with CVDs.

Assessing the predictive efficacy of noninvasive liver fibrosis indices and portal vein diameter in predicting esophageal variceal bleeding in patients with cirrhosis

BackgroundThe objective of this study is to evaluate the diagnostic accuracy of noninvasive serum liver fibrosis markers and portal vein diameter (PVD) in predicting the occurrence of esophageal variceal bleeding (EVB) in patients with cirrhosis.MethodsA cohort comprising 102 individuals diagnosed with cirrhosis was divided into two groups: the P group (without EVB) and the PE group (with EVB). We conducted a comprehensive analysis comparing various noninvasive serum liver fibrosis indices, the Child-Pugh classification, ratios of aspartate aminotransferase to alanine aminotransferase, aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors (FIB-4), PVD, and spleen thickness (SPT) between these groups. Receiver operating characteristic (ROC) curves were constructed for variables showing significant differences between the two groups, with subsequent calculation of the area under the ROC curve (AUROC) for each variable.ResultsSignificant distinctions were noted in the serum liver fibrosis markers between the P and PE groups, encompassing hyaluronic acid (HA), type III procollagen (PC-III), type IV collagen (IV-C), PVD, SPT, and FIB-4 (p < 0.05), as evidenced by univariate analysis findings. The respective AUROC values for these markers were 0.653, 0.706, 0.710, 0.730, 0.660, and 0.633. Additionally, upon integration with PVD, SPT, and FIB4, the AUROC values for liver fibrosis markers surged to 0.793, 0.763, and 0.706 correspondingly, highlighting the enhanced diagnostic potential.ConclusionThe integration of noninvasive liver fibrosis indices and PVD showcased remarkable diagnostic potential in EVB, underscoring its clinical relevance in predicting hemorrhagic events.

MicroRNAs and Other Serological Markers of Liver Fibrosis in Patients with Alcohol-Related Liver Cirrhosis.

Background: It is essential to identify novel non-invasive markers of liver fibrosis for clinical and scientific purposes. Thus, the goal of our survey was to assess the serological expression of selected microRNAs (miRNAs) in patients with alcohol-related liver cirrhosis (ALC) and to correlate them with other existing markers. Methods: Two hundred and thirty-nine persons were enrolled in the study: one hundred and thirty-nine with ALC and one hundred healthy controls. Serological expression of miR-126-3p, miR-197-3p and miR-1-3p was evaluated in all participants. Direct markers of liver fibrosis (PICP, PIIINP, PDGF-AB, TGF-α and laminin) together with indirect indices (AAR, APRI, FIB-4 and GPR) were also assessed. The additional evaluation concerned hematological parameters: MPV, PDW, PCT, RDW, MPR, RPR NLR, PLR and RLR. Results: The expression of miR-197-3p was lower in ALC compared to controls (p < 0.0001). miR-126-3p correlated negatively with AST (p < 0.05) and positively with miR-197-3p (p < 0.001). miR-197-3p correlated with direct markers of liver fibrosis-positively with PDGF-AB (p < 0.005) and negatively with TGF-α (p < 0.01). Significant negative relationships were noticed between miR-1-3p and the number of neutrophils (p < 0.05), TGF-α (p < 0.05) and laminin (p < 0.05). Conclusions: The achieved results and observed correlations prove the potential involvement of the examined miRNAs in the process of liver fibrosis, giving a novel insight into the diagnostics of liver cirrhosis.

GLP-1 Receptor Agonists and Risk for Cirrhosis and Related Complications in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD. To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD. This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health Administration hospitals and associated ambulatory clinics and who initiated either a GLP-1 RA or dipeptidyl peptidase 4 inhibitor (DPP-4i) between January 1, 2006, and June 30, 2022, were included. Patients were followed up from baseline until one of the study outcomes or the end of the study period (December 31, 2022), whichever came first. Each GLP-1 RA new user was propensity score matched in 1:1 ratio to a patient who initiated a DPP-4i during the same month. Separate analyses were conducted among patients without and with cirrhosis at baseline. For patients without cirrhosis, the primary outcome was progression to cirrhosis defined by validated diagnoses codes or a noninvasive marker of liver fibrosis, and secondary outcomes were cirrhosis complications defined both as a composite and individual complications, including decompensation, HCC, or liver transplant, and all-cause mortality. For patients with cirrhosis, the primary outcome was a composite outcome of cirrhosis complications, and secondary outcomes were decompensation, HCC, and all-cause mortality. Of 16 058 patients who initiated GLP-1 RAs, 14 606 did not have cirrhosis (mean [SD] age, 60.56 [10.31] years; 13 015 [89.1%] male), and 1452 had cirrhosis (mean [SD] age, 66.99 [7.09] years; 1360 [93.7%] male) at baseline. These patients were matched to an equal number of patients who initiated a DPP-4i. In patients without cirrhosis, GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of cirrhosis (9.98 vs 11.10 events per 1000 person-years; hazard ratio [HR], 0.86; 95% CI, 0.75-0.98). Similar results were seen for the secondary outcomes. GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of the composite outcome of cirrhosis complications (1.89 vs 2.55 events per 1000 person-years; HR, 0.78; 95% CI, 0.59-1.04) and mortality (21.77 vs 24.43 events per 1000 person-years; HR, 0.89; 95% CI, 0.81-0.98). There were no associations between GLP-1 RA use and outcomes in patients with cirrhosis. In this cohort study, GLP-1 RA use was associated with a lower risk of progression to cirrhosis and mortality among patients with MASLD and diabetes. The protective association was not seen in patients with existing cirrhosis, underscoring the importance of treatment earlier in the disease course.

Helicobacter pylori cagA/vacAs1-m1 strain is associated with high risk of fibrosis in metabolic-dysfunction-associated steatotic liver disease

Introduction and ObjectivesRecent studies have suggested an association between H. pylori and metabolic dysfunction associated steatotic liver disease (MASLD). We aim to evaluate the association of H. pylori virulence genes with non-invasive markers of liver injury and fibrosis in MASLD subjects. Patients and MethodsA total of 362 dyspeptic patients who underwent gastroscopy were selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), gastric biopsies, and H. pylori virulence genes (cagA, vacA) were evaluated. ResultsA cohort comprised of 61 % women and 39 % men with a median age of 52 (40–60) years. MASLD was observed in 42 %, and H. pylori-positive in 45 %. No differences were observed regarding H. pylori status at co-morbid metabolic conditions. In MASLD cohort, H. pylori-positive was associated with higher AST, ALT, FIB-4 and LSM. Indeed, carriers of cagA/vacA-s1/m1-positive allelic combination were associated with higher AST, ALT, FIB-4 and LSM but not cagA/vacA-s1/m1-negative. The OR for high-risk of significant/advanced- fibrosis by VCTE (≥8 kPa) with H. pylori-positive was 2.56 (95 % CI, 1.2–5.75) and for cagA/vacA-s1/-m1-positive allelic carriers was 4.01 (95 % CI, 1.38–11.56), but non-significant association in cagA/vacA-s1/-m1-negative. After adjusting for age, gender, diabetes, BMI and hypertension the OR for VCTE ≥8 kPa with H. pylori-positive was 2.43 (95 % CI, 1.88–12.44), and cagA/vacA-s1/m1-positive allelic carriers was 4.06 (95 % CI, 1.22–14.49). ConclusionsIn our cohort of functional dyspepsia (FD) patients with MASLD, H. pylori was associated with non-invasive markers of liver injury and fibrosis. Carriers of cagA/vacA-s1/m1-positive allelic combination showed an independent risk of significant/advanced fibrosis by VCTE.

Prognostic Value of the Pretransplant Fibrosis-4 Index on Non-Relapse and Overall Mortality following Unrelated Single-Unit Cord Blood Transplantation in Adults

Introduction: The fibrosis-4 (FIB-4) index is a noninvasive marker of liver fibrosis. The FIB-4 index predicts poor outcomes in patients with hepatic and non-hepatic diseases. However, the association of the FIB-4 index with mortality and liver-related clinical outcomes following cord blood transplantation (CBT) is unclear. Methods: We retrospectively evaluated the impact of the pretransplant FIB-4 index on outcomes in 336 adults following single-unit unrelated CBT at our institution. Results: In multivariate analyses, when the FIB-4 index <1.3 group was used as the reference, non-relapse mortality was significantly higher in the FIB-4 index 1.3–2.67 (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.19–5.30) and FIB-4 index >2.67 (HR, 2.34; 95% CI, 1.12–4.90) groups. Overall mortality was significantly higher in the FIB-4 index >2.67 group (HR, 1.66; 95% CI, 1.00–2.73), but with only marginal significance in the FIB-4 index 1.3–2.67 group (HR, 1.59; 95% CI, 0.96–2.64). Hematopoietic recovery, acute and chronic graft-versus-host disease of the liver, and veno-occlusive disease/sinusoidal obstruction syndrome were not associated with the pretransplant FIB-4 index. Conclusion: The pretransplant FIB-4 index is accurate and useful in predicting mortality in adult patients undergoing single-unit unrelated CBT.

Prospective Assessment of Serum Lipid Alterations in Chronic Hepatitis C Patients Treated with Direct Acting Antivirals: Insights Six Months Post Sustained Virological Response.

Background and Objectives: Chronic hepatitis C virus (HCV) infection is intricately linked with dysregulation of lipid metabolism. In particular, cholesterol plays a crucial role in HCV replication. Direct-acting antiviral agents (DAAs) therapy has revolutionized the hepatitis C treatment landscape, achieving high rates of sustained virological response (SVR). However, viral clearance comes with some alterations in lipid-related markers. This prospective study aimed to evaluate the impact of HCV clearance on lipid homeostasis and non-invasive liver fibrosis markers in hepatitis C patients treated with DAAs. Material and Methods: Fifty-two patients with varying degrees of fibrosis treated with DAAs therapy were evaluated at baseline and 24 weeks post-SVR. Lipid profiles and non-invasive liver fibrosis markers were assessed. Results: Our findings revealed an increase in total cholesterol, triglyceride, and LDLc (low-density lipoprotein cholesterol) levels at 24 weeks post-SVR, alongside an improvement in serum liver enzymes. Although improvements in liver stiffness were observed in non-invasive tests, there was an increase in lipid-related markers post-SVR. Conclusions: This suggests a potential increased cardiovascular risk despite improvements in liver function and fibrosis, highlighting the necessity for statin therapy in some cases and extended follow-ups for these patients. These findings underscore the importance of closely monitoring lipid profiles in chronic hepatitis C patients post-SVR, as well as the potential need for statin therapy to mitigate cardiovascular risk. Additionally, extended follow-up is essential to assess long-term outcomes and ensure the optimal management of these patients.

Reliability and Diagnostic Performance of Transient Hepatic Elastography in Chronic Hepatitis C during the Training Phase

Chronic infection with the hepatitis C virus (HCV) is estimated to affect 58 million people worldwide and around 700,000 individuals in Brazil. Various non-invasive markers of hepatic fibrosis have been proposed, such as transient hepatic elastography (THE) using FibroScan®. However, the reliability of the performance, by operators in the training phase is undetermined, which hinders its applicability in clinical practice. Objectives: The present study aimed to evaluate the impact of training an inexperienced operator to perform the examinations using FibroScan® in patients with chronic hepatitis C. Specifically, the frequency of unreliable results throughout the training was assessed. Methods: This is a cross-sectional study with retrospective data collection including compensated chronic hepatitis C patients who underwent the examinations using FibroScan® between March 2014 and December 2016, performed by two researchers. Included patients were divided into two groups based on the operator's experience in the examination: the Experienced Examiner (EE) group and the Examiner in Training (ET) group, with the latter divided into two phases: phase 1, consisting of the first 100 examinations, and phase 2, comprising subsequent examinations. For the reliability analysis, parameters such as success rate (SR), interquartile range (IQR) to median (Md) ratio (IQR/Md), and reliability criteria of Castéra, et al. and Boursier, et al. were used. Results: Between March 2014 and December 2016, 771 adult HCV-infected individuals were evaluated and divided into EE group (n = 161), ET phase 1 (n = 100), and ET phase 2 (n = 158), showing similar demographic, clinical, and laboratory characteristics. SR and IQR/Md ratios were similar among EE, ET phase 1, and ET phase 2 groups. The proportion of reliable results was comparable in all three groups, using Castéra, et al. reliability criteria (92.5%, 92.0%, and 97.5%, respectively) and Boursier, et al. criteria (96.9%, 95.0%, and 98.1%, respectively). Conclusion: A short training period (up to 100 examinations) seems to be sufficient for them to have good clinical applicability in the hands of an operator with initial experience in the method.