Liver fibrosis is considered as a wound healing process in the presence of chronic hepatic injury. A hydrogel (CPDP) based on chitosan-phenol that undergoes fast gelling and owns self-healing and injectable properties was investigated for the effect on regression of liver fibrosis. For the purpose, we established both in vitro and in vivo liver fibrosis models and implanted CPDP hydrogel into the injured liver. The CPDP hydrogel not only provided a suitable microenvironment for hepatocyte spheroids, but also demonstrated a potential for the hepatocyte spheroid-embedded system to mimic the liver tissue in vitro. Furthermore, the urea synthesis of injured hepatocytes cultured on hepatocyte spheroid-embedded CPDP hydrogel was 1.12 times higher than that on hepatocyte spheroid-embedded collagen hydrogel after 7 days of culture, indicating that CPDP hydrogel effectively rescued hepatic function in the injured hepatocytes. Moreover, the hepatic injury was alleviated with improved hepatic function in the liver fibrosis model in vivo. A reduction of approximately 28% in serum AST/ALT ratios and a 70% decrease in the fibrotic area suggested the regression of liver fibrosis after 2 weeks of CPDP hydrogel administration. These findings suggest that CPDP hydrogel holds promise for applications in liver tissue engineering.

Background/Objectives: Bariatric surgery (BS), drugs approved for type-2-diabetes (T2D), obesity, and liver fibrosis (resmetirom) announce the widespread use of fibrosis tests in patients with metabolic liver disease (MASLD). An unmet need is to reduce the uncertainty of biomarkers for the diagnosis of the early stage of clinically significant fibrosis (eF). This can be achieved if three essential but neglected STARD methods (3M) are used, which have a more sensitive histological score than the standard comparator (five-tiers), the weighted area under the characteristic curve (wAUROC) instead of the binary AUROC, and biopsy length. We applied 3M to FibroTest-T2D to demonstrate this reduction of uncertainty and constructed proxies predicting eF in large populations. Methods: For uncertainty, seven subsets were analyzed, four included biopsies (n = 1903), and to assess eF incidence, three MASLD-populations (n = 299,098). FibroTest-T2D classification rates after BS and in outpatients-T2D (n = 402) were compared with and without 3M. In MASLD, trajectories of proxies and incidence against confounding factors used hazard ratios. Results: After BS (110 biopsies), reversal of eF was observed in 16/29 patients (84%) using seven-tier scores vs. 3/20 patients (47%) using five-tier scores (p = 0.005). When the biopsy length was above the median, FibroTest-T2D wAUROC was 0.90 (SD = 0.01), and the wAUROC was 0.88 (SD = 0.1) when the length was below the median (p < 0.001). For the first time, obesity was associated with eF before T2D (p < 0.001), and perimenopausal age with apoA1 and haptoglobin increases (p < 0.0001). Conclusions: Validations of circulating biomarkers need to assess their uncertainty. FibroTest-T2D predicts fibrosis regression after BS. Applying 3M and adjustments could avoid misinterpretations in MASLD surveillance.

Background: Existing non-invasive tests (NITs) for liver fibrosis offer moderate precision and accessibility but are often limited by complexity, reducing their practicality in routine clinical use. This study aimed to evaluate the diagnostic performance of current fibrosis assessment methods and develop a novel, simplified scoring system-the Aspartate Aminotransferase (AST)-Thrombocytopenia-Albumin (ATA) score-to enhance ease of use and clinical applicability. Methods: This study examined past cases of patients with chronic liver disease (CLD) by using magnetic resonance elastography (MRE) to evaluate fibrosis stages. Serum biomarkers were collected, and common fibrosis scores were calculated. Logistic regression identified potential predictors of significant fibrosis, forming the ATA score. Diagnostic performance was assessed, and internal validation was conducted via bootstrap resampling. Results: Among 70 patients, 31.4% had significant fibrosis. Hepatitis B was the most common cause (60.0%), followed by hepatitis C (18.6%) and nonalcoholic fatty liver disease (NAFLD, 15.7%). The ATA score demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.872, comparable to the AST-to-platelet ratio index (APRI; 0.858) and fibrosis-4 index (FIB-4; 0.847). The recommended cut-offs for identifying high-risk patients were ATA score ≥ 2 (specificity 95.8%, sensitivity 50.0%), APRI ≥ 0.50 (specificity 89.6%, sensitivity 68.2%), and FIB-4 ≥ 1.3 (specificity 58.3%, sensitivity 90.9%). Internal validation confirmed model robustness, with an optimism-corrected AUROC of 0.8551. Conclusions: The ATA score offers a straightforward and efficient method for detecting significant fibrosis, demonstrating comparable diagnostic capability to APRI and FIB-4, while being more user-friendly in clinical practice. A score of 0-1 indicates low risk, suitable for clinical follow-up, whereas a score of ≥2 suggests high risk, warranting further evaluation. Integrating the ATA score into clinical workflows can enhance early detection, optimize resource utilization, and improve patient care.

Proton density fat fraction (PDFF) and R2* are noninvasive MRI biomarkers for quantifying fat and iron in abdominal organs. While 3.0 T MRI is widely used clinically, 5.0 T may offer improved accuracy and reliability. With the increasing availability of 5.0 T, assessing its feasibility and utility for quantifying PDFF and R2* in abdominal organs is needed.

To determine the agreement of the PDFF and R2* in the liver, pancreas, kidney, and paraspinal muscle at 2 different field strengths.

Prospective.

A total of 127 participants, including 60 healthy volunteers and 67 with metabolic dysfunction-associated steatotic liver disease (100 women and 27 men, 52 ± 9 years old).

3.0 T and 5.0 T; Chemical shift-encoded multi-echo gradient echo sequence.

PDFF and R2* values in the liver, pancreas, kidney, and paraspinal muscle were measured by three observers to evaluate the interobserver and interfield agreement using two 3.0 T scanners (scanner 1 and scanner 2) and one 5.0 T scanner.

Linear regression, Bland-Altman analyses, and intraclass correlation coefficients (ICCs). The p-value < 0.05 indicated statistically significant.

PDFF and R2* at 5.0 T were strongly correlated with those at two 3.0 T scanners for all organs (R2 = 0.905-0.998 for PDFF; 0.831-0.991 for R2*), indicating high interfield ICCs (0.892-0.993 for PDFF; 0.910-0.981 for R2*). Comparisons between 5.0 T and two 3.0 T scanners showed good interfield agreement for PDFF (mean bias, -0.57% to 0.03%) while a higher bias for R2* (mean bias, -16.53 to -2.64 s-1, 95% LoA, -34.28 to 1.21 s-1) at 5.0 T compared to the comparison between 3T scanners.

5.0 T revealed high interfield agreement between the PDFF and R2* with 3.0 T, which could provide reliable quantification of fat and iron contents in abdominal organs.

2.

Stage 2.

Chronic hepatitis B (CHB) infection represents a significant global public health issue, often leading to hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC) with poor prognoses. Early identification of HBV-LC risk is essential for timely intervention. This study develops and compares nine machine learning (ML) models to predict HBV-LC risk in CHB patients using routine clinical and laboratory data. A retrospective analysis was conducted involving 777 CHB patients, with 50.45% (392/777) progressing to HBV-LC. Admission data consisted of 52 clinical and laboratory variables, with missing values addressed using multiple imputation. Feature selection utilized Least Absolute Shrinkage and Selection Operator (LASSO) regression and the Boruta algorithm, identifying 24 key variables. The evaluated ML models included XGBoost, logistic regression (LR), LightGBM, random forest (RF), AdaBoost, Gaussian naive Bayes (GNB), multilayer perceptron (MLP), support vector machine (SVM), and k-nearest neighbors (KNN). The data set was partitioned into an 80% training set (n = 621) and a 20% independent testing set (n = 156). Cross-validation (CV) facilitated hyperparameter tuning and internal validation of the optimal model. Performance metrics included the area under the receiver operating characteristic curve (AUC), Brier score, accuracy, sensitivity, specificity, and F1 score. The RF model demonstrated superior performance, with AUCs of 0.992 (training) and 0.907 (validation), while the reconstructed model achieved AUCs of 0.944 (training) and 0.945 (validation), maintaining an AUC of 0.863 in the testing set. Calibration curves confirmed a strong alignment between observed and predicted probabilities. Decision curve analysis indicated that the RF model provided the highest net benefit across threshold probabilities. The SHAP algorithm identified RPR, PLT, HBV DNA, ALT, and TBA as critical predictors. This interpretable ML model enhances early HBV-LC prediction and supports clinical decision-making in resource-limited settings.

Antifibrotic trials rely on conventional pathology despite recognized limitations. We compared single-fiber digital image analysis with conventional pathology to quantify the antifibrotic effect of Aramchol, a stearoyl-CoA desaturase 1 inhibitor in development for metabolic dysfunction-associated steatohepatitis.

Fifty-one patients with metabolic dysfunction-associated steatohepatitis enrolled in the open-label part of the ARMOR trial received Aramchol 300 mg BID and had paired pre-post treatment liver biopsies scored by consensus among 3 hepatopathologists, and separately assessed by a digital image analysis platform (PharmaNest) that generates a continuous phenotypic Fibrosis Composite Severity (Ph-FCS) score. Fibrosis improvement was defined as: ≥1 NASH Clinical Research Network (NASH-CRN) stage reduction; "improved" by ranked pair assessment; reduction in Ph-FCS ("any" for ≥0.3 absolute reduction and "substantial" for ≥25% relative reduction). Fibrosis improved in 31% of patients (NASH-CRN), 51% (ranked pair assessment), 74.5% (any Ph-FCS reduction), and 41% (substantial Ph-FCS reduction). Most patients with stable fibrosis by NASH-CRN or ranked pair assessment had a Ph-FCS reduction (a third with substantial reduction). Fibrosis improvement increased with treatment duration: 25% for <48 weeks versus 39% for ≥48 weeks by NASH-CRN; 43% versus 61% by ranked pair assessment, mean Ph-FCS reduction -0.54 (SD: 1.22) versus -1.72 (SD: 1.02); Ph-FCS reduction (any in 54% vs. 100%, substantial in 21% vs. 65%). The antifibrotic effect of Aramchol was corroborated by reductions in liver stiffness, Pro-C3, and enhanced liver fibrosis. Changes in Ph-FCS were positively correlated with changes in liver stiffness.

Continuous fibrosis scores generated in antifibrotic trials by digital image analysis quantify antifibrotic effects with greater sensitivity and a larger dynamic range than conventional pathology.

We investigated the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) and attenuation imaging (ATI) in detecting fibrosis and steatosis in patients with chronic liver disease (CLD), comparing them with established methods.

In 190 patients with CLD, 2D-SWE and vibration-controlled transient elastography (VCTE) were used for liver stiffness measurement (LSM), and ATI and controlled attenuation parameter (CAP) were used for steatosis quantification. The correlations between these new and established methods were analyzed.

Significant correlations were found between 2D-SWE and VCTE (r = 0.78, P < 0.001), and between ATI and CAP (r = 0.70, P < 0.001). Liver stiffness tended to be lower with 2D-SWE compared with that with VCTE, especially in cases with higher LSM, and ATI was less influenced by skin-capsular distance than CAP. Area under the receiver-operating characteristics curves (AUCs) and optimal cut-offs of 2D-SWE for diagnosing liver fibrosis stages F2, F3, and F4 were 0.73 (8.7 kPa), 0.79 (9.1 kPa), and 0.88 (11.6 kPa), respectively. The AUCs and optimal cut-offs of ATI for diagnosing hepatic steatosis grades S1, S2, and S3 were 0.91 (0.66 dB/cm/MHz), 0.80 (0.79 dB/cm/MHz), and 0.88 (0.86 dB/cm/MHz), respectively. A subgroup analysis of 86 patients with metabolic dysfunction-associated steatotic liver disease also demonstrated good performance for 2D-SWE and ATI.

2D-SWE and ATI performed comparably with conventional VCTE and CAP in evaluating CLD, offering reliable alternatives for diagnosing liver fibrosis and steatosis.

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.

Hepatic glycogen storage disease type IX γ2 (GSD IX γ2) is a severe, liver-specific subtype of GSD IX. While all patients with hepatic GSD IX present with similar symptoms, over 95 % of patients with GSD IX γ2 progress to liver fibrosis and cirrhosis. Despite disease severity, the long-term natural history of GSD IX γ2 liver disease progression is not known. Our lab previously characterized the Phkg2-/- mouse model at 3 months of age, demonstrating that the mouse recapitulates the early liver disease phenotype of GSD IX γ2. To understand how liver disease progresses in GSD IX γ2, we characterized the mouse model through 24 months of age. Our study showed for the first time that GSD IX γ2 mice develop liver fibrosis that progresses to cirrhosis. Importantly, we observed that the progression of liver fibrosis is associated with an initial elevation and subsequent decrease of key GSD biomarkers - the latter being a finding that is often considered to be an improvement of disease in patients. In recognition of the unique liver fibrosis pattern and to support future therapeutic investigations using this model, we developed a novel scoring system for GSD IX γ2 mouse liver pathology. Lastly, this work introduces evidence of a dysregulated glycogen metabolism pathway which can serve as an endpoint for future therapeutic evaluation. As we await longitudinal clinical natural history data, these findings greatly expand our understanding of liver disease manifestations in GSD IX γ2 and have notable clinical applications.

Chronic liver disease (CLD) is a global and worldwide clinical challenge, considering that different underlying liver entities can lead to hepatic dysfunction. In the past, blood tests and clinical evaluation were the main noninvasive tools used to detect, diagnose and follow-up patients with CLD; in case of clinical suspicion of CLD or unclear diagnosis, liver biopsy has been considered as the reference standard to rule out different chronic liver conditions. Nowadays, noninvasive tests have gained a central role in the clinical pathway. Particularly, liver stiffness measurement (LSM) and cross-sectional imaging techniques can provide transversal information to clinicians, helping them to correctly manage, treat and follow patients during time. Cross-sectional imaging techniques, namely computed tomography (CT) and magnetic resonance imaging (MRI), have plenty of potential. Both techniques allow to compute the liver surface nodularity (LSN), associated with CLDs and risk of decompensation. MRI can also help quantify fatty liver infiltration, mainly with the proton density fat fraction (PDFF) sequences, and detect and quantify fibrosis, especially thanks to elastography (MRE). Advanced techniques, such as intravoxel incoherent motion (IVIM), T1- and T2- mapping are promising tools for detecting fibrosis deposition. Furthermore, the injection of hepatobiliary contrast agents has gained an important role not only in liver lesion characterization but also in assessing liver function, especially in CLDs. Finally, the broad development of radiomics signatures, applied to CT and MR, can be considered the next future approach to CLDs. The aim of this review is to provide a comprehensive overview of the current advancements and applications of both invasive and noninvasive imaging techniques in the evaluation and management of CLD.

Hepatocyte ballooning (HB) is a significant histological characteristic linked to the advancement of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although clinicians now consider liver biopsy the most reliable method for identifying HB, its invasive nature and related dangers highlight the need for the development of non-invasive diagnostic options.

This study aims to develop a novel methodology that combines deep learning and machine learning techniques to accurately identify and measure hepatobiliary abnormalities in liver ultrasound images.

The research team expanded the dataset, consisting of ultrasound images, and used it for training deep convolutional neural networks (CNNs) such as InceptionV3, ResNet50, DenseNet121, and EfficientNetB0. A hybrid approach, combining InceptionV3 for feature extraction with a Random Forest classifier, emerged as the most accurate and stable method. An approach of dual dichotomy classification was used to categorize images into two stages: healthy vs. sick, and then mild versus severe ballooning.. Features obtained from CNNs were integrated with conventional machine learning classifiers like Random Forest and Support Vector Machines (SVM).

The hybrid approach achieved an accuracy of 97.40%, an area under the curve (AUC) of 0.99, and a sensitivity of 99% for the 'Many' class during the third phase of evaluation. The dual dichotomy classification enhanced the sensitivity in identifying severe instances of HB. The cross-validation process confirmed the strength and reliability of the suggested models.

These results indicate that this combination method can decrease the need for invasive liver biopsies by providing a non-invasive and precise alternative for early identification and monitoring of NAFLD and NASH. Subsequent research will prioritize the validation of these models using larger datasets from multiple centers to evaluate their generalizability and incorporation into clinical practice.

Although metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of cirrhosis worldwide, therapeutic options are limited and the number of clinical trials in MASH-related compensated cirrhosis is low as compared to those conducted in earlier disease stages. Moreover, designing clinical trials in MASH cirrhosis presents a series of challenges regarding the understanding and conceptualization of the natural history, regulatory considerations, inclusion criteria, recruitment, end points and trial duration, among others. The first international workshop on the state of the art and future direction of clinical trials in MASH-related compensated cirrhosis was held in April 2023 at Vall d'Hebron University Hospital in Barcelona (Spain) and was attended by a group of international experts on clinical trials from academia, regulatory agencies and industry, encompassing expertise in MASH, cirrhosis, portal hypertension, and regulatory affairs. The presented Roadmap summarizes important content of the workshop on current status, regulatory requirements and end points in MASH-related compensated cirrhosis clinical trials, exploring alternative study designs and highlighting the challenges that should be considered for upcoming studies on MASH cirrhosis.

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.

Steatosis is defined by hepatocyte accumulation of lipids. Different types of steatosis are described (macro-, medio- and microvacuolar). Macrovacuolar steatosis is a common lesion, mainly observed during metabolic syndrome and excessive alcohol consumption. Steatohepatitis combines steatosis, the presence of ballooned hepatocytes and lobular inflammatory foci. Liver fibrosis is the main consequence of steatohepatitis. Liver biopsy is the gold standard diagnostic test.

Quantitative T1 mapping has the potential to replace biopsy for noninvasive diagnosis and quantitative staging of chronic liver disease. Conventional T1 mapping methods are confounded by fat andB 1 + $$ {B}_1^{+} $$ inhomogeneities, resulting in unreliable T1 estimations. Furthermore, these methods trade off spatial resolution and volumetric coverage for shorter acquisitions with only a few images obtained within a breath-hold. This work proposes a novel, volumetric (3D), free-breathing T1 mapping method to account for multiple confounding factors in a single acquisition.

Free-breathing, confounder-corrected T1 mapping was achieved through the combination of non-Cartesian imaging, magnetization preparation, chemical shift encoding, and a variable flip angle acquisition. A subspace-constrained, locally low-rank image reconstruction algorithm was employed for image reconstruction. The accuracy of the proposed method was evaluated through numerical simulations and phantom experiments with a T1/proton density fat fraction phantom at 3.0 T. Further, the feasibility of the proposed method was investigated through contrast-enhanced imaging in healthy volunteers, also at 3.0 T.

The method showed excellent agreement with reference measurements in phantoms across a wide range of T1 values (200 to 1000 ms, slope = 0.998 (95% confidence interval (CI) [0.963 to 1.035]), intercept = 27.1 ms (95% CI [0.4 54.6]), r2 = 0.996), and a high level of repeatability. In vivo imaging studies demonstrated moderate agreement (slope = 1.099 (95% CI [1.067 to 1.132]), intercept = -96.3 ms (95% CI [-82.1 to -110.5]), r2 = 0.981) compared to saturation recovery-based T1 maps.

The proposed method produces whole-liver, confounder-corrected T1 maps through simultaneous estimation of T1, proton density fat fraction, andB 1 + $$ {B}_1^{+} $$ in a single, free-breathing acquisition and has excellent agreement with reference measurements in phantoms.

We herein report the construction of a robust MRI peptide contrast agent Gd-ICTP with superior selectivity for type I collagen, enabling the accurate and non-invasive detection of hepatic fibrosis in vivo.

Chronic hepatitis B virus (HBV) infection remains a serious health issue, and determining the optimal time for antiviral therapy is challenging. We aimed to assess liver histological changes in patients with HBeAg-positive chronic hepatitis B (CHB) and those with HBeAg-negative CHB who had persistently normal alanine aminotransferase and to determine the association between significant liver injury and various clinical parameters.

We retrospectively included, in this study, 339 treatment-naïve patients with chronic HBV infections who had persistently normal alanine aminotransferase and underwent liver biopsy from 2013 to 2023. Histologic assessment was based on the Metavir scoring system to evaluate the association between clinical characteristics and the severity of liver inflammation and fibrosis.

Among the included participants, 138 were HBeAg-positive and 201 were HBeAg-negative. Lower hepatitis B surface antigen (HBsAg) (P = 0.003) and higher aspartate aminotransferase (AST) (P = 0.002) levels were associated with significant necroinflammation, whereas increasing age (P = 0.004) and lower HBV DNA (P < 0.001) levels were associated with significant fibrosis in HBeAg-positive patients with normal ALT levels. Higher HBV-DNA (P = 0.001) and AST levels(P < 0.001) were associated with significant necroinflammation, and higher AST(P < 0.001) levels were associated with significant fibrosis in HBeAg-negative patients.

A substantial proportion of patients with HBV infection who had normal ALT presented significant liver injury. HBsAg and AST were independent predictive factors for evaluating inflammation, while HBV DNA load and age were independent predictive factors for evaluating fibrosis in the HBeAg-positive group. HBV DNA load and AST were independent predictive factors for evaluating inflammation, while AST were independent predictive factors for evaluating fibrosis in the HBeAg-negative group.

Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has led to, among others, the approval of the first drug specific for metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis). Despite substantial progress, MASLD is still a leading cause of advanced chronic liver disease, including primary liver cancer. This Perspective contextualizes the nomenclature change from nonalcoholic fatty liver disease to MASLD and proposes important considerations to accelerate further progress in the field, optimize patient-centric multidisciplinary care pathways, advance pharmacological, behavioural and diagnostic research, and address health disparities. Key regulatory and other steps necessary to optimize the approval and access to upcoming additional pharmacological therapeutic agents for MASH are also outlined. We conclude by calling for increased education and awareness, enhanced health system preparedness, and concerted action by policy-makers to further the public health and policy agenda to achieve at least parity with other non-communicable diseases and to aid in growing the community of practice to reduce the human and economic burden and end the public health threat of MASLD and MASH by 2030.

Quick and simple parameters are needed to predict mortality in patients with idiopathic pulmonary fibrosis (IPF). In this way, risky patients will have the opportunity to receive early and effective treatment. In this study, we examined whether the Fibrosis-4 index (FIB-4) and systemic immune inflammation index (SII) are associated with mortality in IPF patients.

The study was designed retrospectively. 100 patients diagnosed with IPF were included in the study. Variables between living patients and deceased patients were examined.

Out of a total of 100 patients, 67 were divided into the surviving group and 33 into the non-surviving group. In multivariate analysis, high FIB-4 and SII values were significantly associated with an increased risk of death.

FIB-4 and SII are parameters that can predict mortality in IPF patients. In this way, IPF patients with high mortality risk will be identified earlier and more effective methods will be used in follow-up and treatment.

The influence of advancing fibrosis on graft survival in the context of pediatric liver transplantation accentuates the critical role of protocol-driven liver biopsies, a practice adopted by numerous medical centers. Consequently, the exigency for noninvasive methodologies to assess graft fibrosis assumes heightened importance when conventional clinical and laboratory parameters fail to reveal signs of liver damage.

This study aimed to assess the reliability of transient elastography (TE) in pediatric liver transplant recipients to detect graft fibrosis and compare the results of TE in patients who underwent biopsy.

This prospective cohort study included liver transplanted children who underwent biopsy at Ege University Children's Hospital between October 1, 2021, and October 31, 2022, and a healthy control group. According to TE, fibrosis was detected in 40 patients, and no fibrosis was detected in 50. The median time to develop fibrosis was 100 months (95% CI [83.1-116.8]). A statistically significant positive correlation existed between LSM and METAVIR fibrosis score (r = 0.562, p = 0.001). There was a statistically significant difference in LSM between patients with F2 fibrosis (7.8-8.8 kPa ± 3.2) compared to patients with F0 fibrosis (5.2 kPa ± 0.7) (p = 0.005) and F1 fibrosis (6.1 kPa ± 1.5) (p = 0.041), on ANOVA.

Liver allograft fibrosis is common in long-term follow-up in children who have undergone liver transplantation. Abnormal TE may guide physicians to consider liver biopsy to detect late allograft fibrosis in these children.

The presence and severity of liver fibrosis are important prognostic variables when evaluating people with chronic hepatitis C (CHC). Although liver biopsy remains the reference standard, non-invasive serological markers, such as the four factors (FIB-4) score and the Forns index, can also be used to stage liver fibrosis.

To determine the diagnostic accuracy of the FIB-4 score and Forns index in staging liver fibrosis in people with chronic hepatitis C (CHC) virus, using liver biopsy as the reference standard (primary objective). To compare the diagnostic accuracy of these tests for staging liver fibrosis in people with CHC and explore potential sources of heterogeneity (secondary objectives).

We used standard Cochrane search methods for diagnostic accuracy studies (search date: 13 April 2022).

We included diagnostic cross-sectional or case-control studies that evaluated the performance of the FIB-4 score, the Forns index, or both, against liver biopsy, in the assessment of liver fibrosis in participants with CHC. We imposed no language restrictions. We excluded studies in which: participants had causes of liver disease besides CHC; participants had successfully been treated for CHC; or the interval between the index test and liver biopsy exceeded six months.

Two review authors independently extracted data. We performed meta-analyses using the bivariate model and calculated summary estimates. We evaluated the performance of both tests for three target conditions: significant fibrosis or worse (METAVIR stage ≥ F2); severe fibrosis or worse (METAVIR stage ≥ F3); and cirrhosis (METAVIR stage F4). We restricted the meta-analysis to studies reporting cut-offs in a specified range (+/-0.15 for FIB-4; +/-0.3 for Forns index) around the original validated cut-offs (1.45 and 3.25 for FIB-4; 4.2 and 6.9 for Forns index). We calculated the percentage of people who would receive an indeterminate result (i.e. above the rule-out threshold but below the rule-in threshold) for each index test/cut-off/target condition combination.

We included 84 studies (with a total of 107,583 participants) from 28 countries, published between 2002 and 2021, in the qualitative synthesis. Of the 84 studies, 82 (98%) were cross-sectional diagnostic accuracy studies with cohort-based sampling, and the remaining two (2%) were case-control studies. All studies were conducted in referral centres. Our main meta-analysis included 62 studies (100,605 participants). Overall, two studies (2%) had low risk of bias, 23 studies (27%) had unclear risk of bias, and 59 studies (73%) had high risk of bias. We judged 13 studies (15%) to have applicability concerns regarding participant selection. FIB-4 score The FIB-4 score's low cut-off (1.45) is designed to rule out people with at least severe fibrosis (≥ F3). Thirty-nine study cohorts (86,907 participants) yielded a summary sensitivity of 81.1% (95% confidence interval (CI) 75.6% to 85.6%), specificity of 62.3% (95% CI 57.4% to 66.9%), and negative likelihood ratio (LR-) of 0.30 (95% CI 0.24 to 0.38). The FIB-4 score's high cut-off (3.25) is designed to rule in people with at least severe fibrosis (≥ F3). Twenty-four study cohorts (81,350 participants) yielded a summary sensitivity of 41.4% (95% CI 33.0% to 50.4%), specificity of 92.6% (95% CI 89.5% to 94.9%), and positive likelihood ratio (LR+) of 5.6 (95% CI 4.4 to 7.1). Using the FIB-4 score to assess severe fibrosis and applying both cut-offs together, 30.9% of people would obtain an indeterminate result, requiring further investigations. We report the summary accuracy estimates for the FIB-4 score when used for assessing significant fibrosis (≥ F2) and cirrhosis (F4) in the main review text. Forns index The Forns index's low cut-off (4.2) is designed to rule out people with at least significant fibrosis (≥ F2). Seventeen study cohorts (4354 participants) yielded a summary sensitivity of 84.7% (95% CI 77.9% to 89.7%), specificity of 47.9% (95% CI 38.6% to 57.3%), and LR- of 0.32 (95% CI 0.25 to 0.41). The Forns index's high cut-off (6.9) is designed to rule in people with at least significant fibrosis (≥ F2). Twelve study cohorts (3245 participants) yielded a summary sensitivity of 34.1% (95% CI 26.4% to 42.8%), specificity of 97.3% (95% CI 92.9% to 99.0%), and LR+ of 12.5 (95% CI 5.7 to 27.2). Using the Forns index to assess significant fibrosis and applying both cut-offs together, 44.8% of people would obtain an indeterminate result, requiring further investigations. We report the summary accuracy estimates for the Forns index when used for assessing severe fibrosis (≥ F3) and cirrhosis (F4) in the main text. Comparing FIB-4 to Forns index There were insufficient studies to meta-analyse the performance of the Forns index for diagnosing severe fibrosis and cirrhosis. Therefore, comparisons of the two tests' performance were not possible for these target conditions. For diagnosing significant fibrosis and worse, there were no significant differences in their performance when using the high cut-off. The Forns index performed slightly better than FIB-4 when using the low/rule-out cut-off (relative sensitivity 1.12, 95% CI 1.00 to 1.25; P = 0.0573; relative specificity 0.69, 95% CI 0.57 to 0.84; P = 0.002).

Both the FIB-4 score and the Forns index may be considered for the initial assessment of people with CHC. The FIB-4 score's low cut-off (1.45) can be used to rule out people with at least severe fibrosis (≥ F3) and cirrhosis (F4). The Forns index's high cut-off (6.9) can be used to diagnose people with at least significant fibrosis (≥ F2). We judged most of the included studies to be at unclear or high risk of bias. The overall quality of the body of evidence was low or very low, and more high-quality studies are needed. Our review only captured data from referral centres. Therefore, when generalising our results to a primary care population, the probability of false positives will likely be higher and false negatives will likely be lower. More research is needed in sub-Saharan Africa, since these tests may be of value in such resource-poor settings.

Risk of disease progression and clinical outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with fibrosis stage and presence of "at-risk metabolic dysfunction-associated steatohepatitis (MASH)." Although liver biopsy is considered the gold standard to diagnose MASH and stage of fibrosis, biopsy is infrequently performed in clinical practice and has associated sampling error, lack of interrater reliability, and risk for procedural complications. Noninvasive tests (NITs) are routinely used in clinical practice for risk stratification of patients with MASLD. Several NITs are being developed for detecting "at-risk MASH" and cirrhosis. Clinical care guidelines apply NITs to identify patients needing subspecialty referral. With recently approved Food and Drug Administration treatment for MASH and additional emerging pharmacotherapy, NITs will identify patients who will most benefit from treatment, monitor treatment response, and assess risk for long-term clinical outcomes. In this review, we examine the performance of NITs to detect "at-risk MASH," fibrosis stage, response to treatment, and risk of clinical outcomes in MASLD and MASH.

Hepatic venovenous communications (HVVC) is detectable in more than one-third of cirrhotic patients, where portal hypertension (PHT) tends to present more severely. We aimed to explore the prognostic implications of HVVC in patients with sinusoidal PHT treated by transjugular intrahepatic portosystemic shunt (TIPS).

The multicenter data of patients (2020-2022) undergoing balloon-occluded hepatic venography during TIPS were retrospectively analyzed. Pre-TIPS total bile acids (TBA) levels in portal, hepatic and peripheral veins were compared between groups. The primary endpoint was the development of overt hepatic encephalopathy (HE) within one year after TIPS.

183 patients were eligible and classified by the presence (n = 69, 37.7 %) or absence (n = 114, 62.3 %) of HVVC. The agreement between wedged hepatic venous pressure and portal venous pressure was poor in HVVC group (intraclass correlation coefficients [ICC]: 0.141, difference: 13.4 mmHg, p < 0.001), but almost perfect in non-HVVC group (ICC: 0.877, difference: 0.4 mmHg, p = 0.152). At baseline, patients with HVVC had lower Model for end-stage liver disease scores (p < 0.001), blood ammonia levels (p < 0.001), TBA concentrations in the hepatic (p = 0.011) and peripheral veins (p = 0.049) rather than in the portal veins (p = 0.516), and a higher portosystemic pressure gradient (p = 0.035), suggesting more effective intrahepatic perfusion in this group. Within 1-year post-TIPS, HVVC group had a lower incidence of overt HE (11.7 % vs. 30.5 %, p = 0.004, HR: 0.34, 95 % CI: 0.16-0.74, absolute risk difference [ARD]: -17.4) and an improved liver transplantation-free survival rate (97.1 % vs. 86.8 %, p = 0.021, HR: 0.16, 95 % CI: 0.05-0.91, ARD: -10.3).

For patients with sinusoidal PHT treated by TIPS, the presence of HVVC was associated with a reduced risk of overt HE and a potential survival benefit.

Gene therapy for hemophilia is a groundbreaking treatment approach with promising results and potential to reduce the burden of the disease. However, uncertainties remain, particularly regarding the liver side effects of AAV gene therapy, which are more common in hemophilia A. Unlike some other diseases, such as spinal muscular atrophy, where the target cell for gene therapy is different from the one affected by side effects, hemophilia gene therapy operates within the same cellular domain-the hepatocyte. This overlap is challenging and requires a targeted strategy to mitigate the risks associated with liver injury, which often requires temporary immunosuppressive therapy. A comprehensive approach is essential to increase the efficacy of gene therapy and reduce the likelihood of hepatocyte damage. Key components of this strategy include a thorough pre-gene therapy assessment of liver health, careful post-gene therapy liver monitoring, and prompt therapeutic intervention for loss of transgene expression and liver injury. Collaboration between hematologists and hepatologists is essential to ensure a well-coordinated management plan for patients undergoing hemophilia gene therapy. This review addresses the critical aspect of hepatic comorbidities in patients with hemophilia, emphasizing the need to identify and address these issues prior to initiating gene therapy. It examines the known mechanisms of liver damage and emphasizes the importance of liver monitoring after gene therapy. In addition, the review draws insights from experiences with other AAV-based gene therapies, providing valuable lessons that can guide hemophilia centers in effectively managing liver damage associated with hemophilia gene therapy.

Chronic liver diseases (CLD) stem from various causes and lead to a gradual progression that ultimately may result in fibrosis and eventually cirrhosis. This process is typically prolonged and asymptomatic, characterized by the complex interplay among various cell types, signaling pathways, extracellular matrix components, and immune responses. With the prevalence of CLD increasing, diagnoses are often delayed, which leads to poor prognoses and in some cases, the need for liver transplants. Consequently, there is an urgent need for the development of novel, non-invasive methods for the diagnosis and monitoring of CLD. In this context, serum biomarkers-safer, repeatable, and more acceptable alternatives to tissue biopsies-are attracting significant research interest, although their clinical implementation is not yet widespread. This review summarizes the latest advancements in serum biomarkers for detecting hepatic fibrogenesis and advocates for concerted efforts to consolidate current knowledge, thereby providing patients with early, effective, and accessible diagnoses that facilitate personalized therapeutic strategies.

APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs).

Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations.

Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%).

This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

There is high prevalence of non-alcoholic fatty liver disease in individuals with type 2 diabetes mellitus (T2D), and available evidence suggests higher prevalence of NASH and advanced stages of fibrosis among T2D. Data regarding prevalence of clinically significant liver fibrosis (CSLF) in individuals with T2D is scarce. We investigated the prevalence of transient elastography (TE)-proven CSLF among patients of T2D attending a diabetes clinic at a tertiary care center.

A cross-sectional descriptive evaluation study of 603 consecutive adults with T2D was conducted to detect CSLF using TE. Steatosis was diagnosed using a controlled attenuation parameter >237 dB/m.

The prevalence of CSLF was 22.7%, and the prevalence of steatosis was 58.9% in our study. A higher body mass index (BMI) (P = 0.001), aspartate aminotransferase (AST; P = 0.0001), alanine aminotransferase (ALT; P = 0.0001), and low platelets (P = 0.0001) were independent factors associated with CSLF. Elevated ALT and AST (≥40 units/L) levels were present in only 27.7% and 37.2% of individuals with CSLF, respectively. Twenty-six (4.31%) individuals had LSM > 13.0 kPa.

CSLF is highly prevalent in T2D patients attending a diabetes clinic at a tertiary care center, and the majority of such individuals have normal transaminase levels. Higher BMI, AST, and ALT values and lower platelet counts are associated with liver fibrosis.

The performance and reliability criteria for Aixplorer MACH30 (SS) in chronic liver diseases (CLD) have not been validated.

The objectives were to define the optimal procedure, the accuracy for fibrosis and steatosis diagnosis, and the reliability criteria using SS.

Patients had 2D-shear wave elastography (SWE) and ultraSound-guided controlled attenuation parameter (SCAP) performed in triplicate at the mid-axillary line (MAL), posterior axillary line (PAL), and anterior axillary line (AAL). Performances of SWE and SCAP were defined using transient elastography (TE ≥ 9.5 kPa) and CAP (≥ 275 dB/m) using Fibroscan (FS) as reference and validated with liver biopsy (LB).

FS and SS data from 203 CLD patients were analyzed (55 ± 14 years; 59% male; MASLD 58%). Median TE and CAP were 6.4 kPa (2.5-66.9) and 270 dB/m (141-400). The best technique for the diagnosis of advanced fibrosis and significant steatosis was the median of three SWE values and three SCAP values at MAL, PAL, and AAL with an AUROC of 0.96 [95% CI 0.93-0.98] and 0.91 [95% CI 0.86-0.95]. Only skin-to-liver distance ≥ 2.4 cm (p = 0.012, 95% CI 1.37-13.38) was independently associated with discordance. The accuracy of SWE (≥ 8.5 kPa) and SCAP (≥ 0.44) was analyzed in 58 patients with LB. The PPV and NPV were 50% and 94%, and 71% and 88% for fibrosis and steatosis, respectively.

A reliable diagnosis of advanced fibrosis and significant steatosis can be obtained with the median of three measurements in different liver portions using SS. The only non-reliable criterion is skin-to-liver distance ≥ 2.4 cm.

The efficacy of endoscopic ultrasound-guided liver biopsy (EUS-LB) compared to percutaneous liver biopsy (PC-LB) remains uncertain.

Our data consist of randomized controlled trials (RCTs) comparing EUS-LB to PC-LB, found through a literature search via PubMed/Medline and Embase. The primary outcome was sample adequacy, whereas secondary outcomes were longest and total lengths of tissue specimens, diagnostic accuracy, and number of complete portal tracts (CPTs).

Sample adequacy did not significantly differ between EUS-LB and PC-LB (risk ratio [RR] 1.18; 95% confidence interval [CI] 0.58-2.38; p = 0.65), with very low evidence quality and inadequate sample size as per trial sequential analysis (TSA). The two techniques were equivalent with respect to diagnostic accuracy (RR: 1; CI: 0.95-1.05; p = 0.88), mean number of complete portal tracts (mean difference: 2.29, -4.08 to 8.66; p = 0.48), and total specimen length (mean difference: -0.51, -20.92 to 19.9; p = 0.96). The mean maximum specimen length was significantly longer in the PC-LB group (mean difference: -3.11, -5.51 to -0.71; p = 0.01), and TSA showed that the required information size was reached.

EUS-LB and PC-LB are comparable in terms of diagnostic performance although PC-LB provides longer non-fragmented specimens.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity. We aimed to assess the impact of obesity on the performance of different noninvasive tests, including liver stiffness measurement (LSM) and Agile3+ (A3+), to detect advanced fibrosis (AF) in a population of patients with MASLD encompassing a wide range of BMI values.

A total of 479 patients with MASLD were consecutively included (Lyon Hepatology Institute). Clinical data and noninvasive tests, including FibroTest, LSM, A3+, Fibrosis-4 (FIB-4), magnetic resonance elastography, and liver biopsies, were collected. AF was determined by a composite endpoint, i.e., histological stage ≥ F3, overt diagnosis of cirrhosis by magnetic resonance elastography, or concordant LSM ≥ 9.6 kPa and FibroTest ≥ F3.

The median BMI was 35.0 kg/m2, and the prevalence of AF was 28.6%. Patients with BMI ≥ 35 versus <35 had a lower proportion of AF, i.e., 19.3% versus 38.1% (p < 0.001), but higher indeterminate status for AF (34.2% vs. 15.4%; p < 0.001). In the case of BMI ≥ 35, LSM had lower specificity to rule in AF (77.9%) versus A3+ (90.4%), but A3+ had decreased sensitivity to rule out AF. A sequential LSM/A3+ strategy achieved high specificity to rule in AF and lowered the proportion of indeterminate cases in patients with BMI ≥ 35.

The grade of obesity affects the detection of MASLD-related AF. A sequential use of LSM/A3+ could improve AF detection in patients with BMI ≥ 35.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Its prevalence is increasing with the epidemic of obesity and metabolic syndrome. MASLD progression into metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis may lead to decompensated cirrhosis and development of liver-related events, hepatocellular carcinoma and death. Monitoring disease progression is critical in decreasing morbidity, mortality, need for transplant and economic burden. Assessing for treatment response once FDA-approved medications are available is still an unmet clinical need.

To explore the most up-to-date literature on testing used for monitoring disease progression and treatment response METHODS: We searched PubMed from inception to 15 August 2023, using the following MeSH terms: 'MASLD', 'Metabolic dysfunction-associated steatotic liver disease', 'MASH', 'metabolic dysfunction-associated steatohepatitis', 'Non-Alcoholic Fatty Liver Disease', 'NAFLD', 'non-alcoholic steatohepatitis', 'NASH', 'Biomarkers', 'clinical trial'. Articles were also identified through searches of the authors' files. The final reference list was generated based on originality and relevance to this review's broad scope, considering only papers published in English.

We have cited 101 references in this review detailing methods to monitor MASLD disease progression and treatment response.

Various biomarkers can be used in different care settings to monitor disease progression. Further research is needed to validate noninvasive tests more effectively.

Traditionally, liver biopsy has been the gold standard for fibrosis staging. However, it is an invasive, expensive and uncomfortable procedure that is associated with the risk of complications. Thus, non-invasive methods such as shear wave elastography (SWE) have been developed as potential alternatives to liver biopsy. The aim of this study is to evaluate the diagnostic performance of SWE in pediatric patients with liver fibrosis, specifically in a group of Algerian children and to determine whether this method can be a reliable alternative to liver biopsy.

This prospective, descriptive, monocentric study evaluated the non-invasive diagnostic performance of 2D-SWE in assessing liver fibrosis in pediatric patients. The assessment was carried out using various statistical methods, including Spearman's correlation coefficient, Kappa concordance coefficients, regression analysis, as well as the calculation of area under the receiver operating characteristic (AUROC) values and corresponding cut-off points based on the receiver operating characteristic (ROC) curve.

Our study found that 2D-SWE is strongly correlated with liver biopsy in estimating liver fibrosis in children, with a correlation coefficient greater than 0.8. Furthermore, the Kappa correlation coefficients exceeded 0.8, indicating a strong agreement between 2D-SWE and liver biopsy results. The AUROC value was not less than 0.9 for significant fibrosis and above (≥ F2), indicating that it has satisfactory diagnostic performance in detecting liver fibrosis in children.

2D-SWE shows promise as a non-invasive method for evaluating liver fibrosis in children, offering a potential alternative to liver biopsy. Larger studies are needed to substantiate the findings of this study and to confirm the accuracy and reliability of 2D-SWE for assessing liver fibrosis in children.

Liver histology has prognostic relevance and is used in surveillance and therapeutic strategies. This longitudinal study was designed to evaluate the prognostic relevance of ARFI elastography in comparison to liver histology and to the FIB-4 score in a 5-year observation interval.

Based on the hospital database, patients with an elastography examination of the liver between 2010-2012, a liver biopsy, and a follow-up of 5 years were included in the study. The AUROCs of the events liver-related death, HCC, and liver decompensation/variceal bleeding were calculated for ARFI elastography, liver histology, and FIB-4 and compared using the DeLong test.

In the final analysis 113 patients were included with 30 (26.5 %) patients having high-grade fibrosis and 19 (16.8 %) having liver cirrhosis in histology. The AUROC for liver-related death in the 5-year interval (9.7 %, n=11) was 0.80 [0.68-0.92] for ARFI elastography, 0.79 [0.66-0.92] for liver histology, and 0.66 [0.53-0.79] for FIB-4 with a p-value of 0.83 comparing ARFI to histology and a p-value of 0.02 comparing ARFI to FIB-4. The AUROC for liver decompensation/variceal bleeding (13.3 %, n=15) was 0.86 [0.76-0.94] for ARFI, which is significantly higher than the AUROC of liver histology with 0.71 [0.56-0.86] (p=0.02) and FIB-4 with 0.67 [0.54-0.80] (p=0.003). There was no significant difference for the event HCC when comparing ARFI to histology (p=0.33) or FIB-4 (p=0.14).

The prognostic value of ARFI elastography seems to not be inferior to liver histology regarding liver-related survival and might even outperform histology and the FIB-4 score for predicting some liver-related complications.

This multi-center retrospective study examined the effect of weight loss on the prevention of progression to cirrhosis in a sample exclusively composed of patients with obesity and MASH-related F3 liver fibrosis. Adult patients with obesity and biopsy-confirmed MASH-related F3 liver fibrosis (n = 101) from two liver transplant centers in the US were included in the study. A higher proportion of patients who did not progress to cirrhosis achieved >5% weight loss at follow-up (59% vs. 30%, p = 0.045). In multivariable analysis, patients with >5% weight loss at follow-up had a lower hazard of developing cirrhosis compared to patients with no weight loss or weight gain (HR: 0.29, 95%, CI: 0.08-0.96); whereas, diabetes (HR: 3.24, 95%, CI: 1.21-8.67) and higher LDL levels (HR: 1.02, 95%, CI: 1.01-1.04) were associated with higher hazards of progression to cirrhosis. Weight loss >5% has the potential to prevent disease progression to cirrhosis in patients with obesity and MASH-related F3 liver fibrosis. The realization of this benefit requires weight loss maintenance longer than one year. Larger prospective studies are needed to determine how weight loss impacts other patient-centered outcomes such as mortality, hepatic decompensation, and hepatocellular carcinoma in patients with obesity and MASH-related F3 liver fibrosis.