Non-invasive Fibrosis Markers Research Articles

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 (>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> 0.675 showed similar associations but lacked significant correlation with arterial stiffness in coronary artery disease patients. FIB-4> 2.67 and BARD> 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.

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.

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.

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.

Probiotics may be useful for drug-induced liver dysfunction in patients with depression – A secondary analysis of a randomized clinical trial

Background & AimsThere is a need to identify new treatment options for depression with its comorbidities. Depression often coexists with liver steatosis and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Probiotics might represent a safe option as an adjunctive therapy in patients with depression and possible liver steatosis. The paper presents the secondary analysis of a clinical trial of the effect of probiotic supplementation on the levels of non-invasive markers of liver steatosis and fibrosis in adult patients with depressive disorders. MethodsThe research had a two-arm, parallel-group, prospective, randomized, double-blind, controlled design on probiotics in depression. 116 participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. Here, data from 92 subjects was analyzed. The following were assessed: alanine aminotransferase (ALT), alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio, Hepatic Steatosis Index, Framingham Steatosis Index, as well as non-invasive biomarkers of liver fibrosis (AST to Platelet Ratio Index, Fibosis-4 Index), or baseline socio-demographic, clinical, and laboratory parameters. ResultsThe probiotics did not influence liver steatosis and fibrosis parameters compared with placebo (p=.940 for HSI). However, the subgroup analysis revealed significant differences in liver-related parameters when stratified by the main diagnosis group (better improvement in steatosis indices after probiotics in depressive episode than mixed depression and anxiety disorder patients) or psychotropic medications use (better improvement in ALT-based indices after probiotics in antidepressant-treated subjects than those non-antidepressant-treated). The interplay between probiotics, medications, clinical and metabolic profiles of depression, and the changes in liver-related parameters has been discussed. ConclusionsMultiple factors may modulate the postulated hepatoprotective properties of probiotics efficacy in patients with depression. Further studies with larger sample sizes, different probiotic strains, and longer intervention period are necessary to assess the real significance of probiotics for liver health in this population. ClinicalTrials.gov identifierNCT04756544.

Noninvasive liver fibrosis markers are independently associated with carotid atherosclerosis risk in patients with nonalcoholic fatty liver disease

Objective Nonalcoholic fatty liver disease (NAFLD) is considered an independent risk factor for cardiovascular disease (CVD). The overall morbidity and mortality of CVD increase with higher fibrosis stage in NAFLD. Carotid atherosclerosis (CAS) is an important predictor of cardiovascular events. However, the relationship between liver fibrosis degree and the risk of CAS in NAFLD patients remains uncertain. We aimed to investigate the relationship between noninvasive liver fibrosis markers and CAS risk in patients with NAFLD. Materials and Methods This study included 3,302 participants with NAFLD. Participants were divided into a CAS group and a non-CAS group based on carotid artery ultrasound results. They were then stratified into quartiles using various noninvasive liver fibrosis markers (fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aminotransferase to platelet ratio index (APRI), aminotransferase to alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and Forns index) to assess the associations between these markers and the risk of CAS. Results In the NAFLD population, individuals with CAS exhibited elevated levels of blood pressure, glucose, lipids, and noninvasive liver fibrosis markers (p < 0.001). The higher quartiles of noninvasive liver fibrosis markers, including FIB-4, mFIB-4, AAR, AARPRI, and Forns index, were significantly associated with increased risks of CAS, even after adjusting for multiple CVD risk factors. Conclusions In individuals with NAFLD, increased noninvasive liver fibrosis markers were independently associated with elevated CAS risk, which may be beneficial in assessing the risk of CVD in individuals with NAFLD.

Pegozafermin Added to Background GLP-1 Therapy Led to Greater Improvement in Non-invasive Markers of Liver Fat, Injury and Fibrosis as well as Glycemic Control in NASH Patients with F2/F3 Fibrosis at 24 weeks: A Posthoc Analysis from ENLIVEN

Pegozafermin Added to Background GLP-1 Therapy Led to Greater Improvement in Non-invasive Markers of Liver Fat, Injury and Fibrosis as well as Glycemic Control in NASH Patients with F2/F3 Fibrosis at 24 weeks: A Posthoc Analysis from ENLIVEN

Management of Portal Hypertension in the Older Patient.

Aging is a process of physiological slowing, reduced regenerative capacity and inability to maintain cellular homeostasis. World Health Organisation declared the commencement of population aging globally, largely attributed to improvement in the healthcare system with early diagnosis and effective clinical management. Liver ages similar to other organs, with reduction in size and blood flow. In this review we aim to evaluate the effect of aging in liver disease. Aging causes dysregulation of major carbohydrate, fat and protein metabolism in the liver. Age is a major risk factor for liver fibrosis accelerated by sinusoidal endothelial dysfunction and immunological disharmony. Age plays a major role in patients with liver cirrhosis and influence outcomes in patients with portal hypertension. Transient elastography may be an useful tool in the assessment of portal hypertension. Hepatic structural distortion, increased vascular resistance, state of chronic inflammation, associated comorbidities, lack of physiological reserve in the older population may aggravate portal hypertension in patients with liver cirrhosis and may result in pronounced variceal bleed. Cut-offs for other non-invasive markers of fibrosis may differ in the elderly population. Non-selective beta blockers initiated at lower dose followed by escalation are the first line of therapy in elderly patients with cirrhosis and portal hypertension, unless contraindicated. Acute variceal bleed in the elderly cirrhotic patients can be life threatening and may cause rapid exsanguination due to poor reserve and associated comorbidities. Vasoactive drugs may be associated with more adverse reactions. Early endoscopy may be warranted in the elderly patients with acute variceal bleed. Role of TIPS in the elderly cirrhotics discussed. Management of portal hypertension in the older population may pose significant challenges to the treating clinician.

Non-invasive Serological Markers of Hepatic Fibrosis – Mini Review

Aim: This study examines the pathological outcomes of chronic liver injuries, with a focus on liver fibrosis. It emphasizes understanding the structural changes within the liver that may lead to cirrhosis and functional impairments, crucial for developing targeted antifibrotic therapies. Methods: Our approach reviews existing literature detailing the use of traditional diagnostic methods—biochemical and serological tests alongside liver biopsies. Additionally, we evaluate the reliability and efficacy of non-invasive techniques such as serological test panels and imaging examinations. These methods are compared to understand their viability as supplementary or alternative diagnostic tools to liver biopsy. Significance: Liver fibrosis, if unmanaged, can progress to severe conditions such as cirrhosis and hepatocellular carcinoma, making it vital to understand its progression and treatment options. This study underscores the need for precise and non-invasive diagnostic tools in the clinical management of liver fibrosis, providing insight into the progression of chronic liver diseases and potential therapeutic targets. Conclusion and future perspectives: The research confirms that while liver biopsy remains the definitive method for staging liver fibrosis, its risks and limitations necessitate the use of enhanced non-invasive diagnostic techniques. These methods have shown promising results in accuracy and are critical for broadening clinical applications and patient safety. It is recommended that the scientific community continue to develop and validate non-invasive diagnostic tools. Enhancing the accuracy and reliability of these tools can provide a cost-effective, accessible, and safer alternative for large-scale screening and management of liver fibrosis in asymptomatic populations. Additionally, integrating advancements in radiologic and serological markers can further refine these diagnostic methods, improving overall patient outcomes.

Liver Fibrosis Assessed Via Noninvasive Tests Is Associated With Incident Heart Failure in a General Population Cohort

The aim of this study was to determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association. Using UK Biobank data, we prospectively examined the relationship between noninvasive fibrosis markers (nonalcoholic fatty liver disease [NAFLD] fibrosis score [NFS], Fibrosis-4 [FIB-4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n= 413,860). Cox-regression estimated hazard ratios (HRs) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test. A total of 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high-risk NFS score HR, 1.59; 95% confidence interval [CI],1.47-1.76; P < .0001; FIB-4 HR, 1.69; 95% CI, 1.55-1.84; P < .0001; APRI HR, 1.85; 95% CI, 1.56-2.19; P < .0001; combined fibrosis scores HR, 1.90; 95% CI, 1.44-2.49; P < .0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD), and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3, a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score, and heart failure. In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

Role of Resmetirom, a Liver-Directed, Thyroid Hormone Receptor Beta-Selective Agonist, in Managing Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis

BackgroundResmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, has recently been approved to treat nonalcoholic steatohepatitis (NASH). This meta-analysis aimed to summarize the efficiency and safety of resmetirom in treating NASH. MethodsElectronic databases were searched for randomized controlled trials (RCTs) of resmetirom vs placebo in patients with NASH. The primary outcomes were the changes from baseline in hepatic fat content, liver histology, including NASH resolution, and noninvasive markers of hepatic fibrosis. ResultsThree randomized controlled trials (n = 2231) met the inclusion criteria. Compared to placebo, resmetirom achieved greater reductions from baseline in hepatic fat content assessed by magnetic resonance imaging proton density fat fraction (for resmetirom 80 mg: MD −27.76% [95%CI: −32.84, −22.69]; for resmetirom 100 mg: MD −36.01% [95%CI: −41.54, −30.48]; P < .00001 for both) and FibroScan controlled attenuation parameter (for resmetirom 80 mg: MD −21.45 dBm [95%CI: −29.37, −13.52]; for resmetirom 100 mg: MD −25.51 dBm [95%CI: −33.53, −17.49]; P < .00001 for both). Resmetirom 80 mg outperformed placebo in NASH resolution and ≥2-point nonalcoholic fatty liver disease activity score reduction. Moreover, resmetirom 80 mg and 100 mg were superior to placebo in cytokeratin-18 (M30) reduction. Greater reductions in liver enzymes, lipids, and reverse triiodothyronine were observed in the resmetirom arms with no impact on triiodothyronine. Nausea and diarrhea were more common with resmetirom than with placebo; other adverse events were comparable. ConclusionResmetirom improves hepatic fat content, liver enzymes, and fibrosis biomarkers in NASH patients. Resmetirom generally does not affect thyroid function and is well-tolerated.

Serum non-invasive liver fibrosis markers in patients with COVID-19

Serum non-invasive liver fibrosis markers in patients with COVID-19

No gender differences in the 24-month course of non-invasive liver fibrosis markers after DAA therapy in HCV-mono and HCV/HIV-coinfected patients

Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy. LF was assessed by NILFM: transient elastometry (TE) and several biochemical indexes (APRI, Forns, FIB-4). Men had significantly more advanced LF at baseline than women assessed by NILFM. No LF differences at baseline in age, HIV coinfection course (CD4, HIV viral load), and HCV features (HCV viral load, genotype) were detected. No significant gender differences in LF decline after comparing 24-month and baseline LF values were observed. LF changes after DAA therapy were similar in HCV mono and HCV/HIV coinfected patients and in both sexes. Gender did not influence the course of LF decline after DAA assessed by NILFM: TE (P = 0.8), APRI (P = 0.9), Forns (P = 0.4) and FIB-4 (P = 0.7) by multivariate analysis. No gender differences in the 24 month LF decline after DAA with independence of having HCV mono or HCV/HIV coinfection were found.