FibraChek is a newly developed mass spectrometry (MS) assay kit approved by the National Medical Products Administration (NMPA) of China for quantifying L-tyrosine (Tyr) and taurocholic acid (TCA) in serum, aiding liver fibrosis diagnosis. This study aimed to assess its analytical performance.

The analytical performance was investigated based on NMPA and CLSI guidelines. Method suitability in the clinical context was tested by analyzing clinical samples from liver fibrosis patients confirmed via liver biopsy.

The assay enables simultaneous determination of Tyr and TCA, demonstrating compliance with performance parameters such as linearity, dynamic range, limit of detection (LOD), limit of quantification (LOQ), recovery, repeatability, reproducibility, and stability. It validated a linear range of 20-1000 μmol/L for Tyr and 10.3-618 ng/ml for TCA, maintaining stability after 5 freeze-thaw cycles for 14 months. Components remained stable for up to 7 days at room temperature and 30 days at 2-8 °C. TCA and Tyr were stable for up to 36 months at -20 °C or -80 °C. The method effectively quantified Tyr and TCA in serum from liver fibrosis patients and healthy controls.

This is the first MS-based assay for non-invasive liver fibrosis detection validated for clinical use, providing a rapid and reliable analytical protocol suitable for routine analysis.

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.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease, affecting up to 30% of the global population. MASLD is strongly associated with metabolic risk factors such as obesity and type 2 diabetes, and can progress to advanced stages including cirrhosis and hepatocellular carcinoma. Early diagnosis and accurate staging of fibrosis are critical in managing the disease and preventing complications. While liver biopsy has long been considered the gold standard for assessing fibrosis, it is invasive and carries associated risks. In response, non-invasive tests (NITs) have emerged as essential alternatives for the diagnosis and monitoring of MASLD. Key methods include blood-based biomarkers such as the Fibrosis-4 (FIB-4) score, NAFLD Fibrosis Score (NFS), and Enhanced Liver Fibrosis (ELF) test, as well as imaging modalities like vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). These tests provide safer, more accessible methods for identifying liver fibrosis and guiding clinical management. They are integral in assessing disease severity, guiding treatment decisions, and monitoring disease progression, particularly in light of emerging therapies. NITs have become increasingly recommended by clinical guidelines as they reduce the need for invasive procedures like liver biopsy, improving patient care and outcomes. In conclusion, non-invasive testing plays a crucial role in the effective management of MASLD, offering reliable alternatives for diagnosis and monitoring while minimizing risks associated with traditional invasive methods.

Chronic hepatitis C (CHC) is a health burden with consequent morbidity and mortality. Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment. Noninvasive alternatives for liver biopsy such as transient elastography (TE) and diffusion-weighted magnetic resonance imaging (DW-MRI) are critical needs.

To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC.

This prospective cross-sectional study initially recruited 100 children with CHC virus infection. Sixty-four children completed the full set of investigations including liver stiffness measurement (LSM) using TE and measurement of apparent diffusion coefficient (ADC) of the liver and spleen using DW-MRI. Liver biopsies were evaluated for fibrosis using Ishak scoring system. LSM and liver and spleen ADC were compared in different fibrosis stages and correlation analysis was performed with histopathological findings and other laboratory parameters.

Most patients had moderate fibrosis (73.5%) while 26.5% had mild fibrosis. None had severe fibrosis or cirrhosis. The majority (68.8%) had mild activity, while only 7.8% had moderate activity. Ishak scores had a significant direct correlation with LSM (P = 0.008) and were negatively correlated with both liver and spleen ADC but with no statistical significance (P = 0.086 and P = 0.145, respectively). Similarly, histopathological activity correlated significantly with LSM (P = 0.002) but not with liver or spleen ADC (P = 0.84 and 0.98 respectively). LSM and liver ADC were able to significantly discriminate F3 from lower fibrosis stages (area under the curve = 0.700 and 0.747, respectively) with a better performance of liver ADC.

TE and liver ADC were helpful in predicting significant fibrosis in children with chronic hepatitis C virus infection with a better performance of liver ADC.

The aim of this study was to evaluate the accuracy of LiveBoost™, a gradient boosting (GB)-based prediction system based on standard biochemical values (AST, ALT, platelet count) and age, in Chinese patients with chronic hepatitis B (CHB) and compare its performance with FIB-4 (fibrosis-4 score) and APRI (the aspartate transaminase to platelet ratio index).

This retrospective trial enrolled 454 participants, including 279 CHB patients who underwent liver biopsy and 175 normal controls from 3 centers in China. All participants underwent laboratory blood testing. LiveBoost was constructed using GB and FIB-4 and APRI were calculated from laboratory data.

LiveBoost outperformed APRI and FIB-4 in predicting hepatic fibrosis and cirrhosis. The GB model had an AUROC of 0.977 for CHB diagnosis, 0.804 for early and advanced fibrosis, and 0.836 for non-cirrhosis and cirrhosis, compared to AUROC of 0.554, 0.673 and 0.720 for FIB-4, AUROC of 0.977, 0.652 and 0.654 for APRI.

LiveBoost is a more reliable and cost-effective method than APRI and FIB-4 for assessing liver fibrosis in Chinese patients with CHB.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Recently, the prognosis of NAFLD/NASH has been reported to be dependent on liver fibrosis degree. Liver biopsy remains the gold standard, but it has several issues that must be addressed, including its invasiveness, cost, and inter-observer diagnosis variability. To solve these issues, a variety of noninvasive tests (NITs) have been in development for the assessment of NAFLD progression, including blood biomarkers and imaging methods, although the use of NITs varies around the world. The aim of the Japan NASH NIT (JANIT) Forum organized in 2020 is to advance the development of various NITs to assess disease severity and/or response to treatment in NAFLD patients from a scientific perspective through multi-stakeholder dialogue with open innovation, including clinicians with expertise in NAFLD/NASH, companies that develop medical devices and biomarkers, and professionals in the pharmaceutical industry. In addition to conventional NITs, artificial intelligence will soon be deployed in many areas of the NAFLD landscape. To discuss the characteristics of each NIT, we conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis in this study with the 36 JANIT Forum members (16 physicians and 20 company representatives). Based on this SWOT analysis, the JANIT Forum identified currently available NITs able to accurately select NAFLD patients at high risk of NASH for HCC surveillance/therapeutic intervention and evaluate the effectiveness of therapeutic interventions.

Fibrosis is a common denominator in many pathologies and crucially affects disease progression, drug delivery efficiency and therapy outcome. We here summarize therapeutic and diagnostic strategies for fibrosis targeting in atherosclerosis and cardiac disease, cancer, diabetes, liver diseases and viral infections. We address various anti-fibrotic targets, ranging from cells and genes to metabolites and proteins, primarily focusing on fibrosis-promoting features that are conserved among the different diseases. We discuss how anti-fibrotic therapies have progressed over the years, and how nanomedicine formulations can potentiate anti-fibrotic treatment efficacy. From a diagnostic point of view, we discuss how medical imaging can be employed to facilitate the diagnosis, staging and treatment monitoring of fibrotic disorders. Altogether, this comprehensive overview serves as a basis for developing individualized and improved treatment strategies for patients suffering from fibrosis-associated pathologies.

Background: The Baveno VI Consensus Workshop defined criteria (liver stiffness measured by transient elastography <20 kPa and platelet count >150 × 109 cells/L) to identify those patients with compensated advanced chronic liver diseases (cACLD) who are unlikely to have varices needing treatment (VNTs) and can safely avoid variceal screening endoscopy. This meta-analysis aimed to quantify the safety and efficacy of these criteria in suspected cACLD with liver stiffness >10 kPa and in compensated chronic liver diseases (cCLD) irrespective of liver stiffness. Methods: A systematic search was conducted in nine databases for studies discussed cACLD or cCLD and tested Baveno criteria against variceal screening endoscopy. The main safety and efficacy endpoints were missed VNT rate and spared endoscopy rate (SER), respectively; calculated with the random effect model. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated with the hierarchical summary receiver operating characteristic model. For all outcome measures, 95% confidence intervals were computed. Heterogeneity was tested with I 2-statistics. Results: The search yielded 13 studies including 4,464 patients which reported on suspected cACLD. Pooled missed VNT rate was 0.3% (0.1-0.6%; I 2 = 45.5%), pooled SER was 32.8% (24.8-41.4%; I 2 = 97.0%). Sensitivity, specificity, and AUC of Baveno criteria were 97% (95-98%), 41% (27-57%), and 96% (94-97%), respectively. In the subgroups of cACLD from hepatitis C and B viruses, non-alcoholic fatty liver disease/steatohepatitis, or alcohol, missed VNT rates were 0.0% (0.0-0.3%), 1.2% (0.4-2.2%), 0.0% (0.0-1.3%), or 0.0% (0.0-0.4%), while SERs were 24.2% (20.5-28.1%), 24.9% (21.7-28.4%), 38.6% (10.9-70.8%), or 27.0% (16.9-38.4%), respectively. If we expanded the study population to cCLD, 27 studies included 7,534 patients. Missed VNT rate was 0.2% (0.1-0.5%; I 2 = 39.8%) with a SER of 30.5% (25.2-36.2%; I 2 = 96.1%) while Se, Sp, and AUC were 97% (93-99%), 35% (27-44%), and 80% (77-84%), respectively. Conclusions: The application of Baveno criteria significantly reduces the number of unnecessary variceal screening endoscopies while being safe: cACLD patients with liver stiffness <20 kPa and platelet count > 150 × 109 cells/L carry a very low chance (i.e., 0.3%) of having VNTs. The criteria preserve low missed VNT rate with lower diagnostic performance among cCLD patients.

Conclusive data on the accuracy and clinical applicability of non-invasive screening tests for oesophageal varices (OV) in patients with compensated cirrhosis remain lacking. We conducted this study to identify currently available tests, estimate their diagnostic performance and then exemplify how these could be utilized in clinical practice.

A systematic literature search was performed to identify all primary studies that reported accuracy using oesophagogastroduodenoscopy (OGD) as the gold standard. Sources searched included Ovid MEDLINE, Ovid EMBASE and The Cochrane Library databases.

Twenty-one studies with a total of 2471 patients were identified. Several tests were evaluated in more than three studies. Platelet count/spleen diameter ratio (PSR) had the highest summary area under the curve for detection of any size OV of 0.85 (95% confidence interval 0.78-0.92). At a cut-off of 909 (n = 4 studies) and prevalence rates of 10, 20, 30, 40 and 50% for OV, PSR screening correctly avoided the need for OGD in 70, 62, 55, 47 and 39% of patients, respectively.

PSR appears to be the most accurate and validated non-invasive screening test for OV in patients with compensated cirrhosis. At a cut-off of 909, PSR could be clinically useful to avoid OGDs in a significant proportion of patients.

Chronic liver diseases (CLDs), due to chronic hepatitis C; hepatitis B; nonalcoholic fatty liver diseases (NAFLD); and alcoholic liver disease, are a leading cause of morbidity and mortality globally. Early identification of patients with cirrhosis at high risk of progression to liver-related complications may facilitate timely care and improve outcomes. With risks and misclassification associated with invasive tests, such as liver biopsy, noninvasive imaging modalities for liver fibrosis assessment have gained popularity. Therefore, the American Gastroenterological Association prioritized clinical guidelines on the role of elastography in CLDs, focusing on vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). To inform these clinical guidelines, the current technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for diagnostic accuracy studies. This technical review addresses focused questions related to: (1) comparative diagnostic performance of VCTE and MRE relative to nonproprietary, serum-based fibrosis markers for detection of cirrhosis in patients with hepatitis C virus (HCV), hepatitis B virus (HBV), NAFLD, and alcoholic liver diseases; (2) performance of specific VCTE-defined liver stiffness cutoffs as a test replacement strategy (to replace liver biopsy) in making key decisions in the management of patients with CLDs; and (3) performance of specific VCTE-defined liver stiffness cutoffs as a triage test to identify patients with low likelihood of harboring high-risk esophageal varices (EVs) or having clinically significant portal hypertension (for presurgical risk stratification). This technical review does not address performance of other noninvasive modalities for assessing fibrosis (eg, acoustic radiation force pulse imaging or shear wave elastography) or steatosis (controlled attenuation parameter or magnetic resonance imaging-estimated proton density fat fraction).

Obesity and associated metabolic disorders are related to impairments of the intestinal barrier.

We examined lactulose:mannitol (Lac:Man) permeability in obese individuals with and without liver steatosis undergoing a weight-reduction program to test whether an effective weight-loss program improves gut barrier function and whether obese patients with or without liver steatosis differ in this function.

Twenty-seven adult, nondiabetic individuals [mean ± SD body mass index (BMI; in kg/m²): 43.7 ± 5.2; 78% with moderate or severe liver steatosis] were included in the follow-up intervention study (n = 13 by month 12). All patients reduced their weight to a mean ± SD BMI of 36.4 ± 5.1 within 12 mo. We assessed barrier functions by the oral Lac:Man and the fecal zonulin tests. Insulin resistance was assessed by the homeostatic model assessment index (HOMA), and liver steatosis by sonography and the fatty liver index (FLI).

The Lac:Man ratio and circulating interleukin (IL) 6 concentration decreased during intervention from 0.080 (95% CI: 0.073, 0.093) to 0.027 (95% CI: 0.024, 0.034; P < 0.001) and from 4.2 ± 1.4 to 2.8 ± 1.6 pg/mL (P < 0.01), respectively. At study start, the Lac:Man ratio was higher in patients with moderate or severe steatosis than in those without any steatosis (P < 0.001). The Lac:Man ratio tended to correlate with HOMA (ρ = 0.55, P = 0.052), which correlated with FLI (ρ = 0.75, P < 0.01). A multiple-regression analysis led to a final model explaining FLI best through BMI, waist circumference, and the Lac:Man ratio.

Intestinal permeability is increased in obese patients with steatosis compared with obese patients without. The increased permeability fell to within the previously reported normal range after weight reduction. The data suggest that a leaky gut barrier is linked with liver steatosis and could be a new target for future steatosis therapies. This trial was registered at clinicaltrials.gov as NCT01344525.

Transient elastography (TE) is hampered in some patients by failures and unreliable results. We hypothesized that real time two-dimensional shear wave elastography (2D-SWE), the FibroScan XL probe, and repeated TE exams, could be used to obtain reliable liver stiffness measurements in patients with an invalid TE examination.

We reviewed 1975 patients with 5764 TE exams performed between 2007 and 2014, to identify failures and unreliable exams. Fifty-four patients with an invalid TE at their latest appointment entered a comparative feasibility study of TE vs. 2D-SWE.

The initial TE exam was successful in 93% (1835/1975) of patients. Success rate increased from 89% to 96% when the XL probe became available (OR: 1.07, 95% CI 1.06-1.09). Likewise, re-examining those with a failed or unreliable TE led to a reliable TE in 96% of patients. Combining availability of the XL probe with TE re-examination resulted in a 99.5% success rate on a per-patient level. When comparing the feasibility of TE vs. 2D-SWE, 96% (52/54) of patients obtained a reliable TE, while 2D-SWE was reliable in 63% (34/54, p < 0.001). The odds of a successful 2D-SWE exam decreased with higher skin-capsule distance (OR = 0.77, 95% CI 0.67-0.98).

Transient elastography can be accomplished in nearly all patients by use of the FibroScan XL probe and repeated examinations. In difficult-to-scan patients, the feasibility of TE is superior to 2D-SWE.

To evaluate transient elastography (TE) as a noninvasive tool in staging liver fibrosis compared with liver biopsy and morphometry in children with different chronic liver diseases.

A total of 90 children [50 with chronic hepatitis C virus (HCV), 20 with autoimmune hepatitis (AIH) and 20 with Wilson disease] were included in the study and underwent liver stiffness measurement (LSM) using TE. Liver biopsies were evaluated for fibrosis, qualitatively, by Ishak score and quantitatively by fibrosis area fraction (FAF) using digital image analysis (morphometry). LSM was correlated with fibrosis and other studied variables using spearman correlation. A stepwise multiple regression analysis was also performed to examine independent factors associated with LSM. Different cut-off values of LSM were calculated for predicting individual fibrosis stages using receiver-operating characteristic curve. Cut-off values with optimal clinical performance (optimal sensitivity and specificity simultaneously) were selected.

The majority of HCV group had minimal activity (80%) and no/mild fibrosis (72%). On the other hand, the majority of AIH group had mild to moderate activity (70%) and moderate to severe fibrosis (95%) and all Wilson disease group had mild to moderate activity (100%) and moderate to severe fibrosis (100%). LSM correlated significantly with both FAF and Ishak scores and the correlation appeared better with the latter (r = 0.839 vs 0.879, P < 0.0001 for both). LSM discriminated individual stages of fibrosis with high performance. Sensitivity ranged from 81.4% to 100% and specificity ranged from 75.0% to 97.2%. When we compared LSM values for the same stage of fibrosis, they varied according to the different etiologies. Higher values were in AIH (16.15 ± 7.23 kPa) compared to Wilson disease (8.30 ± 0.84 kPa) and HCV groups (7.43 ± 1.73 kPa). Multiple regression analysis revealed that Ishak fibrosis stage was the only independent variable associated with higher LSM (P < 0.0001).

TE appears reliable in distinguishing different stages of liver fibrosis in children. However, its values vary according to the disease type. For that, a disease-specific estimation of cut-off values for fibrosis staging is worthy.