Invasive right heart catheterization plays a central role in identifying pulmonary hypertension (PH) disorders. However, non-invasive biomarkers of portopulmonary hypertension (PoPH) are required. Liver stiffness evaluated by FibroScan® is useful for the assessment of liver fibrosis in patients with chronic liver diseases. This study sought to investigate the utility of liver stiffness for the classification of PoPH among precapillary PH patients.

A total of 46 patients [38 females, median (interquartile range) age 63.0 (50.8-72.0) years old] with precapillary PH were divided into a PoPH group (N = 6) and a non-PoPH group (N = 40) based on the presence of portosystemic shunts and/or portal hypertension with hepatic venous pressure gradient >5 mmHg.

The PoPH group showed higher cardiac index and lower pulmonary vascular resistance than the non-PoPH group. Other hemodynamic variables and liver fibrosis biomarkers such as fibrosis-4 index and albumin-bilirubin score were comparable between the 2 groups. Liver stiffness measurements in the PoPH group were significantly higher than those in the non-PoPH group [12.8 kPa (9.4-17.3 kPa) vs 4.15 kPa (3.30-5.50 kPa), p < 0.001]. The cut-off value for the classification of PoPH was 8.50 kPa from the receiver operating characteristic curve (area under curve 0.979, 95 % Confidence interval 8.50 kPa - 11.00 kPa).

Liver stiffness evaluated by transient elastography may be a non-invasive biomarker to detect the liver status that caused PoPH among precapillary PH patients.

Liver steatosis (LS) is a condition that is characterised by hepatic fat accumulation unrelated to significant alcohol consumption. This study explored the serum proteomic profile associated with LS in people living with HIV (PLWH).

The study cohort comprised 266 PLWH, 21.1% and 78.9% of whom had LS and no LS, respectively. Serum samples were analysed using liquid chromatography coupled with mass spectrometry (LC-MS).

Among the 220 proteins detected, afamin (AFM) and apolipoprotein F (APOF) were identified as proteins associated with LS. Differential expression of AFM and APOF was observed in under- and normoweight patients, emphasising their potential as biomarkers in patients without overweight or obesity.

These findings suggest that the identified proteins could serve as promising biomarkers of LS in PLWH, paving the way for further investigations into the roles of these proteins in LS development in this unique population.

To evaluate the diagnostic performance of multisample point shear wave elastography (pSWE) for liver fibrosis in obese patients with metabolic dysfunction-associated steatotic liver disease (MASLD) using liver biopsy as the reference standard and to compare it with the FIB-4 index and aspartate to platelet ratio index (APRI).

Patients with obesity who met the diagnostic criteria for MASLD between April 2023 and December 2024 were selected for this retrospective single-centre study. Liver stiffness measurements were reported as median values of measurements, and Auto-pSWVs (m/s) were measured using the multisample pSWE technique. The diagnostic performance of auto shear wave velocities (Auto-pSWVs), FIB-4 index and APRI for significant fibrosis (≥F2) and advanced fibrosis (≥F3) of the liver was evaluated and compared using receiver operating characteristic curves with liver biopsy as the criterion. The correlation between Auto-pSWVs and the clinical variables of the subjects was evaluated.

Data from 241 patients were analysed. Auto-pSWVs were positively correlated with the pathological diagnosis of liver fibrosis (r=0.34, p<0.001), and the liver fibrosis stage was an independent risk factor for Auto-pSWVs (beta coefficient: 0.42, p< 0.001). In addition, Auto-pSWVs was superior to FIB-4 index and APRI when comparing the diagnostic performance of significant liver fibrosis (≥F 2) and advanced fibrosis (≥F3) (p < 0.05). The AUC of Auto-pSWVs was 0.75 (95% CI 0.66-0.85) and 0.96 (95% CI 0.89-1.0) in the ≥ F2 and ≥ F3 groups, respectively. The cut-off value for Auto-pSWVs were determined as follows: grade F2 ≥ 1.02 m/s; and grade F3 ≥ 1.30 m/s.

Multisample pSWE appears to be a valuable tool for the diagnosis of liver fibrosis in obese patients with MASLD.

Management of ultrasound (US)-guided percutaneous liver biopsy (PLB) lacks standardisation. Despite the low risk of major complications (< 1%), repeated blood counts and up to 4 h of in-hospital observation are typically recommended. We aimed to assess complication rates and predictors in a large cohort of patients undergoing US-PLB across three Italian tertiary centres. We included all patients undergoing US-PLB from January 2018 to December 2023. We collected clinical, biochemical and procedural features (needle type, insertions number, observation time and antiplatelet/anticoagulant regimens). Safety was assessed by the incidence of pain and major complications, including vasovagal reaction, bleeding, pneumothorax, shock, hospitalisation and death.

Among 1838 patients (mean age 55.1 years, 46.1% females, mean BMI 25.1 kg/m2, 74% parenchymal PLB), few were on anticoagulant/antiplatelet therapy (4.2%/16.2%); mean platelet count and PT INR were 209.7 × 103/mm3 and 1.04; 17 patients (0.9%) received prophylactic therapy (blood components, thrombopoietin receptor agonists or vitamin K). Needle aspiration was predominant (92%). During a mean time of observation of 5.4 ± 2.0 h, 134/1838 patients reported pain (7.4%). Major complications were few (26, 1.4%), with 14 episodes of transient hypotension (0.8%); 10 bleeding events (0.5%); 1 pneumothorax; 1 abscess formation; 1 haemobilia; and 1 episode of chest pain. Hospitalisation was rare (12, 0.7%), primarily for bleeding management. No fatalities were recorded. Pain was the sole significant independent predictor of major complications (18/26, HR 30.6, p < 0.05), particularly when reported within the first hour post-procedure (15/18, 83.3%).

Major complications following US-PLB are few and strongly associated with early post-procedural pain. In the absence of pain within the first hour, extended monitoring may be unnecessary, allowing for earlier patient discharge.

The diagnosis of liver fibrosis is critical in managing chronic liver diseases. The EASL guidelines now recognize ultrasound elastography as a valuable, non-invasive method for assessing liver fibrosis. However, there is a lack of uniform use and reporting of the technique. The purpose of this position paper was to provide guidance on using ultrasound elastography techniques and interpreting results in clinical practice.

A French national consensus panel of experts in radiology and hepatology, convened by SIAD (Société d'Imagerie Abdominale et Digestive) and AFEF (Association Française pour l'Etude du Foie), developed a position statement paper on best practices in ultrasound elastography. They were established using an online Delphi methodology that included an online panel discussion and item preparation. Consensus was achieved when ≥ 80 % of the participants agreed with a specific recommendation.

The accuracy and reliability of ultrasound elastography results could be significantly affected by a variety of operator-related and patient-related factors. Standard recommendations have been established in two areas, including recommendations for measurements and factors affecting results and reliability, and guidelines for standardized reporting of ultrasound elastography results.

This position paper is a comprehensive and accessible guide for clinicians that outlines best practices and standardized protocols to improve the reliability of ultrasound elastography assessments.

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health challenge, with evidence indicating that hepatic inflammation and fibrosis are heterogeneous processes. Purpose To measure liver mechanical property heterogeneity using MR elastography (MRE) and evaluate its potential as a biomarker for tissue inflammation and fibrosis in patients with MASLD. Materials and Methods Mechanical tissue heterogeneity in MASLD was assessed at three-dimensional vector MRE pixel-wise histogram analysis of shear stiffness and loss modulus in preclinical and clinical studies. The preclinical study involved 25 rats that were examined monthly, whereas the clinical study analyzed data from 179 participants across two prospective studies (September 2015 to November 2022), including some who underwent bariatric surgery at pretreatment and posttreatment MRE examinations. Mean and coefficient of variation (CV) of shear stiffness and loss modulus were calculated for each examination. Nonparametric tests and Spearman correlation coefficient were used to compare MRE-derived tissue mechanics with biopsy-confirmed fibrosis and inflammation and assess correlations with portal pressure and histopathologic hepatic fibrosis. Results The preclinical study showed that, in cirrhotic livers, CV of loss modulus positively correlated with portal pressure and fibrosis area ratio variation (ρ = 0.52 [P = .008] and 0.55 [P = .005], respectively). The clinical study showed that, in 10 healthy volunteers (median age, 36.5 years; IQR, 34.0-38.8 years; five females) and 169 participants with MASLD (median age, 50.1 years; IQR, 41.0-58.2 years; 118 females), CV of sheer stiffness (from 0.12 to 0.30 in healthy participants to participants with stage 4 fibrosis) and loss modulus (from 0.31 to 0.51 in healthy participants to participants with grade 3 inflammation) increased with increasing severity of fibrosis and inflammation, respectively. In 36 participants who underwent bariatric surgery, the CV of sheer stiffness decreased at the 1-year follow-up, from 0.16 (IQR, 0.14-0.18) to 0.14 (IQR, 0.12-0.16) (P = .009). Conclusion Tissue mechanical heterogeneity assessed at MRE positively correlated with progression of MASLD, demonstrating potential as a biomarker for liver disease severity and therapeutic intervention. ClinicalTrials.gov Identifier: NCT02565446 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Moura Cunha in this issue.

Patients with mild autonomous cortisol secretion (MACS) are at increased risk of cardiometabolic outcomes, such as hyperglycemia, metabolic syndrome, and cardiovascular diseases. Nonalcoholic fatty liver disease (NAFLD) is also associated with increased cardiometabolic risk. We aimed to investigate the prevalence and predictors of NAFLD in metabolically healthy subjects with MACS.

Forty patients with MACS and 60 patients with nonfunctioning adrenal incidentaloma (NFAI) matched for age, gender, and body mass index were included. We excluded various diseases that may lead to NAFLD, such as diabetes, cardiovascular diseases, and liver disorders. Non-alcoholic fatty liver disease was evaluated with unenhanced abdominal computed tomography and noninvasive fatty liver indices.

Patients with MACS had lower mean liver attenuation values (Hounsfield units, HU) than those with NFAI (p = 0.001). Visceral adiposity index, hepatic steatosis index, and fatty liver index were higher in the MACS group than in the NFAI group (p = 0.009, p = 0.002, p = 0.023, respectively). However, there was no significant association between the mean liver HU value and these indices. There was a significant association between serum cortisol level after the 1 mg dexamethasone suppression test (DST) and mean liver HU value independent of other traditional risk factors in various models performed in multivariable linear regression analysis.

Our findings suggest that MACS is associated with an increased risk of NAFLD, and serum cortisol level after 1 mg DST is an independent predictor of NAFLD in patients with MACS.

The objective of this study is to elucidate the sensitizing effect of mesoporous silica nanoparticles (MSNs) on shear wave elastography (SWE) and to investigate the potential application of MSNs as a sensitizer to enhance the sensitivity of SWE in the diagnosis of metabolic-associated steatohepatitis (MASH).

The in vitro gelatin models with varying ratios were assessed using SWE to identify the gelatin ratio that most closely approximates with human liver stiffness. Following the characterization of the dispersion properties of MSNs, in vitro models incorporating MSNs of different particle sizes were developed. The variations in shear wave velocity (SWV) within these models were measured and subjected to statistical analysis using SWE. The biocompatibility of the MSNs was evaluated, and the MSN solution was subsequently administered into a MASH animal model. The sensitizing effect of SWE on rat liver was then analyzed statistically.

The in vitro model demonstrated that MSNs with smaller particle sizes (100 nm and 200 nm) facilitated the propagation of SWV, thereby enhancing the sensitivity of SWE (P < 0.05). Additionally, the cell viability and hemolysis ratio of 100 nm MSNs were superior to those of 200 nm MSNs (P < 0.05). In vivo animal model experiments indicated that 100 nm fluorescence-modified MSNs could penetrate the MASH liver and elevate the liver stiffness value as measured by SWE.

MSNs have the potential to enhance the sensitivity of SWE in the diagnosis of MASH. This approach offers novel insights for improving the efficacy of SWE in clinical diagnostic and therapeutic applications.

Background/Objectives: Clinical imaging techniques, such as magnetic resonance imaging and computed tomography, play a vital role in supporting clinicians by aiding disease diagnosis and facilitating the planning of appropriate interventions. This is particularly important in malignant conditions like hepatocellular carcinoma, where accurate image segmentation, delineating the liver and tumor, is a critical initial step in optimizing diagnosis, staging, and treatment planning, including interventions like transplantation, surgical resection, radiotherapy, portal vein embolization, and other procedures. Therefore, effective segmentation methods can significantly influence both diagnostic accuracy and treatment outcomes. Method: In this paper, we propose a deep learning-based approach aimed at accurately segmenting the liver in medical images, thus addressing a critical need in hepatic disease diagnosis and treatment planning. We consider a U-Net architecture with residual connections to capture fine-grained anatomical details. We also take into account the prediction explainability, aiming to highlight, in the image under analysis, the areas that are symptomatic for a certain segmentation. In detail, by exploiting the U-Net architecture, two different models are trained with two annotated datasets of computed tomography medical images, resulting in four different experiments. Results: We consider two different datasets to improve robustness and generalization across diverse patient populations and imaging conditions. Experimental results demonstrate that the proposed method obtains interesting performances, with an accuracy ranging from 0.81 to 0.93. Conclusions: We thus show that the proposed method can provide a reliable and efficient solution for automated liver segmentation, promising significant advancements in clinical workflows and precision medicine.

Introduction: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and thyroid hormones has been established, but the direct effects of TSH on the liver, potentially leading to steatosis, and insulin resistance remain unclear. Objective: To investigate the association of TSH levels with MASLD and insulin resistance. Methods: We conducted a cross-sectional study of 8825 euthyroid individuals. Subjects were volunteers or patients referred to the International Center for Nutritional Status Assessment (University of Milan, Italy) undergoing clinical examination and blood drawing for thyroid function tests and liver indices calculation. Liver outcomes were fatty liver index (FLI), hepatic steatosis index (HSI), and FIB-4. All associations were adjusted for fT4 and confounders. Results: We found a positive association of TSH levels with FLI (β = 2.76; p < 0.001) and HSI (β = 0.58, p < 0.001). This relationship remained significant when stratifying by sex and BMI category, except for HSI in normal weight individuals. No significant association was found between TSH and hepatic fibrosis or insulin resistance. Conclusions: We found a positive association between TSH levels and MASLD in euthyroid individuals independently of fT4, sex, and BMI. Insulin resistance and hepatic fibrosis appear unrelated to TSH, independent of fT4 and BMI. The specific role of TSH in MASLD warrants further investigation.

tTo assess the evolving role of endoscopy assessment for esophageal varices in cirrhosis.

The approach to screening endoscopy for varices has significantly changed in the last 10 years with the refinement of non-diagnostic tests. Non-invasive diagnostic methods have reduced the need of upper endoscopies for variceal screening in patients with compensated cirrhosis, focusing primarily on those with ambiguous risk assessments or contraindications to non-selective beta-blockers (NSBBs). In contrast, decompensated cirrhosis patients require more frequent endoscopic evaluations due to their heightened risk of complications and the potential benefit of combination therapy (NSBBs + variceal ligation). In patients with hepatocellular carcinoma (HCC) the performance of non-invasive tests is suboptimal and most patients require endoscopy. Emerging applications of artificial intelligence (AI) can assist in patient triage and the interpretation of endoscopic findings, potentially improving care. Further research is essential to validate these technologies within clinical practice and optimize their integration into patient management strategies.

The absence of hepatic fat in advanced fibrosis has been documented in metabolic dysfunction-associated steatotic liver disease (''burnt-out" MASLD). However, whether hepatic fat loss occurs continuously with fibrosis progression is controversial. We proposed a "burning-out" concept to describe this process and analyze the long-term outcomes of "burnt-out" and "burning-out" MASLD.

We included a MASLD cohort from 16 centers, including 3273 individuals with baseline histology and 5455 with serial vibration-controlled transient elastography measurements during the follow-up. "Burnt-out" MASLD was defined by steatosis grade ≤S1 and fibrosis stage ≥F3. Trajectory analysis identified "burning-out" patients with continuous trends of decreasing controlled attenuation parameter and increasing liver stiffness measurement values.

Of 3273 patients with histologic evaluation included, 435 had "burnt-out" MASLD. Compared with those with pronounced steatosis in advanced fibrosis, patients with "burnt-out" had higher risks of all-cause mortality (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.14-4.02), liver-related events (LREs; HR, 1.77; 95% CI, 1.12-2.78), and hepatic decompensation (HR, 1.83; 95% CI, 1.11-3.01). Of 5455 patients with vibration-controlled transient elastography included for trajectory analysis, 176 were identified as "burning-out" MASLD. The incidence rates of all-cause mortality, LREs, and decompensation were 7.28, 26.47, and 21.92 per 1000 person-years in "burning-out" patients, respectively. The "burning-out" group had higher cumulative incidences of adverse outcomes than patients with consistently high controlled attenuation parameter and moderate/low liver stiffness measurement values (P < .0001).

Continuous hepatic fat loss accompanied by fibrosis progression, referred to as "burning-out," was observed in advanced MASLD and associated with high rates of all-cause mortality, LREs, and hepatic decompensation.

Endoscopic ultrasound shear wave elastography (EUS-SWE) is a novel modality for liver stiffness measurement. The aims of this study are to evaluate the performance and reliability of EUS-SWE for detecting advanced liver disease in a prospective cohort.

EUS-SWE measurements were prospectively obtained from patients undergoing EUS between August 2020 and March 2023. Liver stiffness measurements were compared between patients with and without advanced liver disease (ALD), defined as stage ≥3, to determine diagnostic accuracy for advanced fibrosis and portal hypertension. Logistic regression was performed to identify variables that impact the reliability of EUS-SWE readings. Select patients underwent paired magnetic resonance elastography (MRE) for liver fibrosis correlation.

Patients with ALD demonstrated higher liver stiffness compared to healthy controls (left lobe: 17.6 vs. 12.7 kPa, P <0.001; median right lobe: 24.8 vs. 11.0 kPa, P <0.001). The area under the receiver operator characteristic (AUROC) for the detection of ALD was 0.73 and 0.80 for left and right lobe measurements, respectively. General anesthesia was associated with reliable EUS-SWE liver readings (odds ratio: 2.73, 95% CI: 1.07-7.39, P =0.040). Left lobe measurements correlated significantly with MRE with an increase of 0.11 kPa (95% CI: 0.05-0.17 kPA) for every 1 kPa increase on EUS-SWE. D.

SWE is a promising technology that can readily be incorporated into standard EUS examinations for the assessment of ALD.

Background: Non-alcoholic fatty liver disease (NAFLD) has become a growing public health problem worldwide, and dietary interventions have important potential in the prevention and treatment of NAFLD. Moreover, previous animal studies have shown that flaxseed has a good improvement effect in animal NAFLD models. Objectives: Assess whether flaxseed powder could improve the liver lipid content in patients with NAFLD. Methods: In this 12-week randomized controlled clinical trial, 50 patients were randomly assigned to the flaxseed group (n = 25) and the control group (n = 25). The flaxseed group received 30 g d-1 flaxseed powder orally before lunch or dinner along with health education, while the control group received only health education. The primary outcome was the intrahepatic lipid content assessed by the proton density fat fraction estimated by magnetic resonance imaging, and secondary outcomes were body composition measurements, liver function, and glucolipid metabolism. Results: Patients in the flaxseed group showed significantly lower liver fat content, body fat percentage, obesity index, visceral fat area, serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) levels after a 12-week intervention compared to pre-intervention levels, while serum apolipoprotein A1 (Apo A1) and high-density lipoprotein cholesterol (HDL-C) levels were significantly increased, with all differences being statistically significant (P < 0.05). Analysis of the gut microbiota showed that, at the phylum level, flaxseed intervention significantly increased the abundance of Bacteroides and Actinobacteria, while decreasing the ratio of Firmicutes to Bacteroidetes. At the genus level, the relative abundance of Clostridium_sensu_stricto_1, Parasutterella, Lachnospiraceae_NK4A136_group, Eubacterium_xylanophilum_group, and Bifidobacterium in the gut microbiota of the flaxseed group was significantly higher than that of the control group (P < 0.05), whereas the relative abundance of Coriobacteriaceae_UCG-002 was significantly lower than that of the control group (P < 0.05). Conclusions: Flaxseed powder intervention for 12 weeks had the effect of improving liver lipid deposition, liver function, body composition indicators, and lipid metabolism in patients with NAFLD. It also regulated the gut microbiota in NAFLD patients, increasing the abundance of beneficial bacteria while reducing harmful bacteria. This suggested that flaxseed is one of the natural and effective foods for improving NAFLD.

It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments, but its diagnostic methods remain unmet. Extracellular matrix protein 1 (ECM1) has previously been reported to be a key factor in the induction and progression of liver fibrosis. However, little is known about the use of ECM1 as a biomarker to evaluate fibrosis. In a CCl4-induced mouse model of liver fibrosis, the present study demonstrated that ECM1 decreased with gradually increasing fibrosis. Using biopsy as a reference, the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis, but there were no significant changes between fibrosis stage 2 and stage 0-1. To improve the performance of ECM1, age, platelet count, and ECM1 concentration were combined to calculate an EPA (ECM1-platelet-age) score (ranging from 0 to 10). The areas under the receiver operating characteristic curve of the EPA scores for the detection of F⩾2, F⩾3, and F4 were 0.6801, 0.7377, and 0.8083, respectively, which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio, APRI score, or FIB-4 score. In HBV patients following antiviral treatment, the dynamics of the EPA score depended on the status of liver fibrosis development. The accuracy of the EPA score in predicting fibrosis regression and progression was 66.00% and 71.43%, respectively, while that of the LSM, another useful method for monitoring hepatic fibrosis changes during treatment, was only 52.00% and 7.14%, respectively. Compared with healthy controls, there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection, MAFLD, ALD, PBC, and DILI. These findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury, and further examinations or medical care are needed. In conclusion, the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liver fibrosis. Additionally, ECM1 alone is an indicator for distinguishing patients with liver injury from healthy controls.

Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) stems from disrupted lipid metabolism in the liver, often linked to obesity, type 2 diabetes, and dyslipidemia. In Mexico, where obesity affects 36.9% of adults, MASLD prevalence has risen, especially with metabolic syndrome affecting 56.31% by 2018. MASLD can progress to Metabolic Dysfunction-Associated Steatohepatitis (MASH), affecting 5.27% globally, leading to severe complications like cirrhosis and hepatocellular carcinoma. Background: Visceral fat distribution varies by gender, impacting MASLD development due to hormonal influences. Insulin resistance plays a central role in MASLD pathogenesis, exacerbated by high-fat diets and specific fatty acids, leading to hepatic steatosis. Lipotoxicity from saturated fatty acids further damages hepatocytes, triggering inflammation and fibrosis progression in MASH. Diagnosing MASLD traditionally involves invasive liver biopsy, but non-invasive methods like ultrasound and transient elastography are preferred due to their safety and availability. These methods detect liver steatosis and fibrosis with reasonable accuracy, offering alternatives to biopsy despite varying sensitivity and specificity. Conclusions: MASLD as a metabolic disorder underscores its impact on public health, necessitating improved awareness and early management strategies to mitigate its progression to severe liver diseases.

This study assessed the impact of hepatic fibrosis on the diagnostic performance of the controlled attenuation parameter (CAP) in quantifying hepatic steatosis in patients with chronic hepatitis B (CHB).

CHB patients who underwent liver stiffness measurement (LSM) and CAP assessment using transient elastography before liver resection between 2019 and 2022 were retrospectively evaluated. Clinical data included body mass index (BMI) and laboratory parameters. The histologically determined hepatic fat fraction (HFF) and fibrosis stages were reviewed by pathologists blinded to clinical and radiologic data. The Pearson correlation coefficient between CAP and HFF was calculated. The diagnostic performance of CAP for significant hepatic steatosis (HFF ≥10%) was assessed using areas under the receiver operating curve (AUCs), stratified by fibrosis stages (F0-1 vs. F2-4). Factors significantly associated with CAP were determined by univariable and multivariable linear regression analyses.

Among 399 CHB patients (median age 59 years; 306 men), 16.3% showed significant steatosis. HFF ranged from 0% to 60%. Of these patients, 9.8%, 19.8%, 29.3%, and 41.1% had fibrosis stages F0-1, F2, F3, and F4, respectively. CAP positively correlated with HFF (r=0.445, P<0.001). The AUC of CAP for diagnosing significant steatosis was 0.786 (95% confidence interval [CI], 0.726 to 0.845) overall, and significantly lower in F2-4 (0.772; 95% CI, 0.708 to 0.836) than in F0-1 (0.924; 95% CI, 0.835 to 1.000) (P=0.006). Multivariable analysis showed that BMI (P<0.001) and HFF (P<0.001) significantly affected CAP, whereas LSM and fibrosis stages did not.

CAP evaluations of significant hepatic steatosis are less reliable in CHB patients with significant or more advanced (F2-4) than with no or mild (F0-1) fibrosis.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD), is a chronic liver disorder associated with disturbances in lipid metabolism. The disease is prevalent worldwide, particularly closely linked with metabolic syndromes such as obesity and diabetes. Magnetic Resonance Proton Density Fat Fraction (MRI-PDFF), serving as a non-invasive and highly quantitative imaging assessment tool, holds promising applications in the diagnosis and research of MASLD. This paper aims to comprehensively review and summarize the applications and research progress of MRI-PDFF technology in MASLD, analyze its strengths and challenges, and anticipate its future developments in clinical practice.

Percutaneous liver biopsy (PC-LB) has long been the usual method for acquisition of liver tissue. Recently, endoscopic ultrasound-guided liver biopsy (EUS-LB) has gained popularity as an alternative modality. We aimed to compare the efficacy and safety of EUS-LB versus PC-LB.

We systematically searched PubMed, Embase, and the Cochrane Library databases for randomized controlled trials (RCTs) comparing EUS-LB with PC-LB published until October 20, 2023. The primary outcome was diagnostic adequacy. Secondary outcomes were: the number of complete portal tracts (CPTs), longest sample length (LSL), total sample length (TSL), post-procedure pain scores, and adverse events (AEs), including overall AEs and AEs excluding minor post-procedure symptoms. We compared binary outcomes using risk ratios (RRs) and continuous outcomes using the mean difference (MD) or standardized mean difference (SMD), with 95%CIs.

Four RCTs (258 patients) were included. The EUS-LB group presented lower post-procedure pain scores (SMD -0.58, 95%CI -0.95 to -0.22) than the PC-LB group. Both groups performed similarly in terms of diagnostic adequacy (RR 1.0, 95%CI 0.96 to 1.04), number of CPTs (MD 2.57, 95%CI -4.09 to 9.22), LSL (MD -2.91 mm, 95%CI -5.86 to 0.03), TSL (MD 4.16 mm, 95%CI -10.12 to 18.45), overall AEs (RR 0.54, 95%CI 0.20 to 1.46), and AEs excluding minor post-procedure symptoms (RR 1.65, 95%CI 0.21 to 13.02).

This meta-analysis suggests that EUS-LB is as safe and effective as PC-LB and is associated with lower post-procedure pain scores.Registration on PROSPERO: CRD42023469469.

Accurate and reliable diagnosis and monitoring of hepatic fibrosis is increasingly important given the variable natural history in chronic liver disease (CLD) and expanding antifibrotic therapeutic options targeting reversibility of early-stage cirrhosis. This highlights the need to develop more refined and effective noninvasive techniques for the dynamic assessment of fibrogenesis and fibrolysis.

We conducted a literature review on PubMed, from 1 December 1970, to 1 November 2024, to evaluate and compare available blood-based and imaging-based noninvasive tools for hepatic fibrosis diagnosis and monitoring. Simple scores such as FIB-4 and NAFLD fibrosis score are suitable for excluding significant or advanced fibrosis, while tertiary centers should adopt complex scores and liver stiffness measurement as part of a secondary diagnostic and more comprehensive evaluation. Moreover, the advent of multiomics for high-resolution molecular profiling, and integration of artificial intelligence for noninvasive diagnostics holds promise for revolutionizing fibrosis monitoring and treatment through novel biomarker discovery and predictive omics-based algorithms.

The increased shift toward noninvasive diagnostics for liver fibrosis needs to align with personalized medicine, enabling more effective, tailored management strategies for patients with liver disease in the future.

Liver fibrosis represents a common sequela of nonalcoholic fatty liver disease (NAFLD) and other chronic liver diseases. Noninvasive liver fibrosis scores (LFSs) aim to evaluate the severity of liver fibrosis. Whether LFSs can predict the risk of future cardiovascular events (CVEs) remains unclear. This systematic review aimed to clarify the association between liver fibrosis and CVEs by studying the value of LFSs, namely the Fibrosis-4 (FIB-4) Index for Liver Fibrosis score and the NAFLD Fibrosis Score (NFS), for predicting CVEs.

PubMed, Scopus, Web of Science, and Cochrane Library were searched for relevant prospective studies. Retrieved articles were screened to confirm their eligibility for the systematic review. We evaluated the quality of the included studies using the National Institutes of Health tool.

Twelve studies of high to fair quality were included in this systematic review. Of note, 10/12 studies reported an independent association between high LFSs and the risk of CVEs, cardiovascular mortality, and all-cause mortality (all P < 0.05). In addition, an advanced histological grade of liver fibrosis (grade 3 or 4) was suggestive of CVE occurrence. NAFLD also appeared to be associated with a higher risk of CVEs at any severity of fibrosis (all P < 0.05).

The findings of this review suggest that liver fibrosis in patients with NAFLD is an independent predictor of future adverse CVEs, cardiovascular mortality, and all-cause mortality. Noninvasive and easy-to-perform LFSs, including FIB-4 score and the NFS, appear useful in predicting such events in patients with a spectrum of cardiovascular diseases and the general population without known cardiovascular disease.

To evaluate the diagnostic performance of ultrasound-derived fat fraction (UDFF) and clinical prediction models in assessing hepatic steatosis grades in MASLD patients, with liver biopsy as reference standard.A total of 85 obese patients who were found to have fatty liver by B-mode ultrasound and underwent UDFF measurement, with liver biopsy available, were enrolled. The diagnostic performance of UDFF, clinical prediction models including fatty liver index (FLI), hepatic steatosis index (HSI), ZheJiang University index (ZJU index) and lipid accumulation product (LAP) for hepatic steatosis was assessed. The areas under receiver operating characteristics curves (AUROCs) were utilized to determine the diagnostic efficacy. DeLong test was used to compare the diagnostic performance of different noninvasive methods for hepatic steatosis. The UDFF values of S1, S2 and S3 groups were 17.53 ± 7.49%, 25.00 ± 5.41% and 27.58 ± 6.55%, respectively (P < 0.001). UDFF values were significantly positively correlated with histologic steatosis grades (r = 0.531, P < 0.001). In the ≥ S2 group, the AUROC of UDFF was higher than that of FLI and LAP (P < 0.05), but not significantly different from that of HSI and ZJU index (P > 0.05). In the ≥ S3 group, the AUROC of UDFF was higher than that of FLI, ZJU index and LAP (P < 0.05), but not significantly different from that of HSI (P > 0.05). The UDFF proves effective in assessing hepatic steatosis in patients with MASLD, and its diagnostic efficacy exceeded that of FLI and LAP, but there was no significant difference with HSI, ZJU index in the ≥ S2 group, and with HSI in the ≥ S3 group.

Background: Chronic liver disease (CLD) presents a significant global health burden, demanding effective tools for diagnosis and monitoring. Traditionally, liver biopsy has been the gold standard for evaluating liver fibrosis and other chronic liver conditions. However, biopsy's invasiveness, associated risks, and sampling variability indicate the need for reliable, noninvasive alternatives. This review examines the utility of noninvasive tests (NITs) in assessing liver disease severity, progression, and therapeutic response in patients with CLD. Result: Key modalities discussed include serum biomarker panels (e.g., FIB-4, APRI, ELF), imaging techniques like transient elastography, and magnetic resonance elastography, each offering unique benefits in fibrosis staging. Emerging biomarkers such as extracellular vesicles and circulating microRNAs show promise in early detection and personalized monitoring. Comparative studies indicate that while no single NIT matches biopsy precision, combinations of these modalities improve diagnostic accuracy and patient outcomes by reducing unnecessary biopsies. Moreover, NITs are instrumental in monitoring dynamic changes in liver health, allowing for more responsive and patient-centered care. Conclusions: Challenges remain, including standardization across tests, cost considerations, and the need for larger, diverse population studies to validate findings. Despite these limitations, NITs are increasingly integrated into clinical practice, fostering a paradigm shift toward noninvasive, accessible liver disease management. Continued advancements in NITs are essential for improved patient outcomes and will likely shape the future standard of care for CLD.

A straightforward, reliable, and noninvasive method for predicting the development of liver-related events (LRE) in primary biliary cholangitis (PBC) has not been attained thus far. This study investigated whether serum autotaxin (ATX) could predict LRE in patients with PBC.

This retrospective multicenter investigation included 190 biopsy-proven untreated patients with PBC. All subjects were followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, esophagogastric varices, ascites, and hepatic encephalopathy, was investigated in relation with ATX levels at the time of liver biopsy.

During the median follow-up period of 9.7 years, LRE were observed in 22 patients (11.6%). The area under the receiver operating characteristic curve and cutoff value of serum ATX for predicting LRE were 0.80 and 1.086 mg/L, respectively. Patients with serum ATX ≥1.086 had a significantly higher cumulative incidence of LRE compared with patients with ATX < 1.086 (33.3% vs 3.6%, P < 0.00001). Notably, the predictive capability of ATX for LRE in patients with PBC surpassed that of FIB-4, ALBI, APRI, and Mac-2-binding protein glycan isomer. A multivariate Cox proportional hazards model revealed ATX as an independent associated factor for LRE (hazard ratio 6.24, 95% confidence interval 1.87-20.80, P = 0.003) along with Nakanuma stage (hazard ratio 2.75, 95% confidence interval 1.52-4.99, P < 0.001). These results were closely replicated in a serologically diagnosed PBC validation cohort (n = 32).

Serum ATX levels may serve as a predictive marker for LRE in patients with PBC.

This article uses three different probabilistic convolutional architectures applied to ultrasound image analysis for grading Fatty Liver Content (FLC) in Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) patients. Steatosis is a new silent epidemic and its accurate measurement is an impelling clinical need, not only for hepatologists, but also for experts in metabolic and cardiovascular diseases. This paper aims to provide a robust comparison between different uncertainty quantification strategies to identify advantages and drawbacks in a real clinical setting.

We used a classical Convolutional Neural Network, a Monte Carlo Dropout, and a Bayesian Convolutional Neural Network with the goal of not only comparing the goodness of the predictions, but also to have access to an evaluation of the uncertainty associated with the outputs.

We found that even if the prediction based on a single ultrasound view is reliable (relative RMSE [5.93%-12.04%]), networks based on two ultrasound views outperform them (relative RMSE [5.35%-5.87%]). In addition, the results show that the introduction of a "not confident" category contributes to increase the percentage of correctly predicted cases and to decrease the percentage of mispredicted cases, especially for semi-intrusive methods.

The possibility of having access to information about the confidence with which the network produces its outputs is a great advantage, both from the point of view of physicians who want to use neural networks as computer-aided diagnosis, and for developers who want to limit overfitting and obtain information about dataset problems in terms of out-of-distribution detection.

Shear wave (SW) elastography is used to evaluate metabolic dysfunction-associated steatotic liver disease (MASLD) pathophysiology. Increased elasticity due to fibrosis and increased viscosity due to necrosis and inflammation affect SW. Assessing fibrosis, the most prognostically relevant pathology, is critical. Viscosity is evaluated using the dispersion slope (DS); however, cut-off values that affect SW values are unclear. We compared the ultrasound imaging parameters (SW for viscoelasticity; DS for viscosity) with pathological findings.

Patients (n = 159) who underwent liver biopsy and SW and DS assessments at our hospital were included. Fibrosis stage and inflammation grade cut-off values were calculated from SW, DS, and liver biopsy results using receiver operating characteristic curves. Cases in which liver biopsy results were inconsistent with SW results were used to determine the effect of viscosity on SW values. DS was examined in the Correct and Incorrect Diagnosis groups, which were categorized based on the concordance between SW and liver biopsy results. Dispersion slope cut-off values between the two groups were calculated.

Fibrosis stage cut-off values by SW (m/s) were: ≥F2, 1.62; ≥F3, 1.74; and F4, 1.97. Inflammation grade cut-off values by DS (m/s/kHz) were: ≥A1, 11.6; ≥A2, 14.5; and A3, 16.1. The Correct/Incorrect Diagnosis groups had 25/70 patients. The DS cut-off value for both groups was 13.2 m/s/kHz.

Shear wave and DS are useful for evaluating liver fibrosis and inflammation in MASLD. For DS > 13.2 m/s/kHz, SW may be affected by the increased viscosity owing to inflammation. In such patients, caution should be used when determining/interpreting values.

Chronic liver disease diagnoses depend on liver biopsy histopathological assessment. However, due to the limitations associated with biopsy, there is growing interest in the use of quantitative digital pathology to support pathologists. We evaluated the performance of computational algorithms in the assessment of hepatic inflammation in an autoimmune hepatitis in which inflammation is a major component.

Whole-slide digital image analysis was used to quantitatively characterize the area of tissue covered by inflammation [Inflammation Density (ID)] and number of inflammatory foci per unit area [Focal Density (FD)] on tissue obtained from 50 patients with autoimmune hepatitis undergoing routine liver biopsy. Correlations between digital pathology outputs and traditional categorical histology scores, biochemical, and imaging markers were assessed. The ability of ID and FD to stratify between low-moderate (both portal and lobular inflammation ≤1) and moderate-severe disease activity was estimated using the area under the receiver operating characteristic curve (AUC).

ID and FD scores increased significantly and linearly with both portal and lobular inflammation grading. Both ID and FD correlated moderately-to-strongly and significantly with histology (portal and lobular inflammation; 0.36≤R≤0.69) and biochemical markers (ALT, AST, GGT, IgG, and gamma globulins; 0.43≤R≤0.57). ID (AUC: 0.85) and FD (AUC: 0.79) had good performance for stratifying between low-moderate and moderate-severe inflammation.

Quantitative assessment of liver biopsy using quantitative digital pathology metrics correlates well with traditional pathology scores and key biochemical markers. Whole-slide quantification of disease can support stratification and identification of patients with more advanced inflammatory disease activity.

During recent decades, the metabolic dysfunction-associated steatohepatitis (MASH) field has witnessed several paradigm shifts, including the recognition of liver fibrosis as the main predictor of major adverse liver outcomes. Throughout this evolution, liver histology has been recognised as one of the main hurdles in MASH drug development due to its invasive nature, associated cost, and high inter- and intra-reader variability. Collective experience demonstrates the importance of consistency in the central reading process, where consensus methods have emerged as appropriate ways to mitigate against well-known challenges. Using crystalized knowledge in the field, stakeholders should collectively work towards the next paradigm shift, where non-invasive biomarkers will be considered surrogate endpoints for accelerated approval. In this review, we provide an overview of the evolution of the regulatory histology endpoints and the liver biopsy reading process, within the MASH trial landscape, over recent decades; we then review the biggest challenges associated with liver biopsy endpoints. Finally, we discuss and provide recommendations on the best practices for liver biopsy evaluation in MASH drug development.

Background and study aims In patients with ascites, percutaneous liver biopsy is generally contraindicated. Because endoscopic ultrasound-guided tissue acquisition (EUS-TA) allows tissue sample obtention from the digestive tract lumen, a biopsy without the intervention of ascites may prevent adverse events (AEs). This study aimed to evaluate the safety of EUS-TA for focal liver lesions in the presence of ascites. Patients and methods A retrospective study was conducted using medical records of cases in which EUS-TA was performed on focal liver lesions between 2016 and 2022. Study participants were classified into two groups: those with ascites and those without it, and the outcomes were compared. The primary outcome was AEs. Results We included 109 cases of EUS-TA for focal liver lesions. Ascites was present in 20.1% of cases (22/109) and absent in 79.8% of cases (87/109). There were no significant differences between the two groups in clinical backgrounds and EUS-TA procedure, although fine-needle biopsy needles were significantly more frequently used in patients without ascites. In the ascites group, puncture without intervening ascites was successful in 90.9% of cases (20/22). The incidence of AEs was 4.5% (1/22) in the ascites group and 1.1% (1/87) in the non-ascites group, showing no significant difference. The two AEs were mild self-limiting abdominal pain. Conclusions In focal liver lesions with ascites, EUS-TA allows biopsy without the intervention of ascites in most cases. The incidence of AEs did not differ significantly between patients with and without ascites.

To investigate whether patients undergoing percutaneous liver mass biopsy (PLMB) can be safely discharged following a two-hour monitoring period.

A multi-center prospective analysis was conducted for 375 patients (196 males and 179 females), mean age 63 ± 12.45 years (range 37-89) who underwent PLMB between August 2023 and March 2024. Patients were monitored for 24 h, and complications were classified as minor or major. The timing of complications was categorized into three groups: within the first two hours, between the 2nd and 24th hours, and within 1 week after 24 hours.

Minor complications occurred in 18.93% (71/375) and major complications in 2.13% (8/375). Most minor complications (80.2%, 57/71) appeared within the first two hours, 12.7% (9/71) between 2 and 24 h, and 7.1% (5/71) after 24 h. All major complications (62.5%, 5/8) except late-onset cases, occurred within the first two hours. No major complications occurred between 2 and 24 h. Late-onset major complications occurred in 37.5% (3/8) after 24 h.

The two-hour monitoring period did not adversely impact patient management regarding minor complications and is safe for identifying all major complications except for late-onset ones. Extending the post-biopsy recovery period does not significantly improve patient care.

To assess the feasibility and performance of MR elastography (MRE) for quantifying liver fibrosis in patients with and without hepatic iron overload.

This retrospective single-center study analyzed 139 patients who underwent liver MRI at 3 Tesla including MRE (2D spin-echo EPI sequence) and R2* mapping for liver iron content (LIC) estimation. MRE feasibility and diagnostic performance between patients with normal and elevated LIC were compared.

Patients with elevated LIC (21%) had significantly higher MRE failure rates (24.1% vs. 3.6%, p < 0.001) compared to patients with normal LIC (79%). For those with only insignificant to mild iron overload (LIC < 5.4 mg/g; 17%), MRE failure rate did not differ significantly from patients without iron overload (8.3% vs. 3.6%, p = 0.315). R2* predicted MRE failure with fair accuracy at a threshold of R2* ≥ 269 s-1 (LIC of approximately 4.6 mg/g). MRE showed good diagnostic performance for detecting significant (≥ F2) and severe fibrosis (≥ F3) in patients without (AUC 0.835 and 0.900) and with iron overload (AUC 0.818 and 0.889) without significant difference between the cohorts (p = 0.884 and p = 0.913). For detecting cirrhosis MRE showed an excellent diagnostic performance in both groups (AUC 0.944 and 1.000, p = 0.009).

Spin-echo EPI MRE at 3 Tesla is feasible in patients with mild iron overload with good to excellent performance for detecting hepatic fibrosis with a failure rate comparable to patients without iron overload.

There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference.

Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis.

The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73).

Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC.

Understanding the dynamics of serum Mac-2 binding protein glycosylation isomer (M2BPGi) remains pivotal for hepatitis C virus (HCV) patients' post-sustained virologic response (SVR12) through direct-acting antivirals (DAAs).

We compared areas under receiver operating characteristic curves (AUROCs) of M2BPGi, FIB-4, and APRI and assess M2BPGi cutoff levels in predicting fibrosis stages of ≥F3 and F4 utilizing transient elastography in 638 patients. Variations in M2BPGi levels from pretreatment to SVR12 and their association with pretreatment alanine transaminase (ALT) levels and fibrosis stage were investigated.

The AUROCs of M2BPGi were comparable to FIB-4 in predicting ≥F3 (0.914 vs 0.902, P = 0.48) and F4 (0.947 vs 0.915, P = 0.05) but were superior to APRI in predicting ≥F3 (0.914 vs 0.851, P = 0.001) and F4 (0.947 vs 0.857, P < 0.001). Using M2BPGi cutoff values of 2.83 and 3.98, fibrosis stages of ≥F3 and F4 were confirmed with a positive likelihood ratio ≥10. The median M2BPGi change was -0.55. Patients with ALT levels ≥5 times ULN or ≥F3 demonstrated more pronounced median decreases in M2BPGi level compared to those with ALT levels 2-5 times ULN and <2 times ULN (-0.97 vs -0.68 and -0.44; P < 0.001) or with < F3 (-1.52 vs -0.44; P < 0.001).

Serum M2BPGi is a reliable marker for advanced hepatic fibrosis. Following viral clearance, there is a notable M2BPGi decrease, with the extent of reduction influenced by ALT levels and fibrosis stage.