Elevated liver biochemistries are associated with increased risk of negative outcomes in patients with primary biliary cholangitis (PBC).

To evaluate whether longitudinal monitoring of liver biochemistries and fibrosis scores provides additional prognostic value and to assess the relationship between the degree of elevation of multiple biomarkers within different alkaline phosphatase (ALP) strata.

Adults with PBC were identified from Komodo's Healthcare Map. A Cox proportional hazards model examined time to first occurrence of hospitalisation due to hepatic decompensation, liver transplantation, or death as a function of the proportion of time during follow-up that liver biochemistries and fibrosis scores exceeded thresholds. Within ALP strata (ALP ≤ upper limit of normal [ULN]; ALP>ULN to ≤ 1.67 × ULN; ALP > 1.67 × ULN), separate multivariate Cox hazard models assessed the association between time-varying covariates and the composite endpoint.

Overall, 3974 patients were included; 88.2% were female, with a mean age of 59.4 years. The median follow-up was 2.5 years. Increasing magnitude and duration beyond established thresholds of ALP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), AST/platelet ratio index (APRI) and fibrosis-4 (FIB-4) were associated with increased risk of negative outcomes. Elevated ALT, AST, TB, APRI and FIB-4 were associated with increased risk of negative outcomes across all ALP strata.

Prolonged elevation of multiple hepatic biomarkers and fibrosis scores is associated with a greater risk of negative clinical outcomes, underscoring the importance of ongoing monitoring beyond the guideline-recommended initial treatment response to guide timely treatment decisions and improve PBC management.

An association between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and the development of extrahepatic malignancies has been demonstrated. However, the association of fibrosis with extrahepatic cancer is unclear. Our study aimed to test the long-term association between liver fibrosis marker and the incidence of hepatic and extrahepatic malignancies.

A retrospective cohort study of a nationally representative sample, following 763 752 adult Clalit health services members without pre-existing liver-related diagnoses or malignancies for 14.67 years. The adjusted association between baseline liver Fibrosis-4 score (FIB-4; FIB-4 ≥ 2.67 indicated presumed advanced fibrosis), assessed from routine laboratory measurements, and incident cancer was assessed through multivariable Cox regression models.

The study included 763 752 people (mean age 54.3 ± 8.2 years, 43.9% males). Presumed advanced fibrosis was associated with a 16% greater risk for malignancy compared to the risk of those with no fibrosis (hazard ratio (HR) = 1.16; 95% CI, 1.10-1.22), adjusting for age, sex, ethnicity, socioeconomic status, peripherality index, baseline smoking, and obesity. The association of advanced fibrosis with malignancy was stronger when the age-specific FIB-4 cutoff was applied (HR = 1.40; 1.34-1.46) and in a subsample of subjects with MASLD diagnosis at baseline (HR = 1.43; 1.12-1.83). The association remained robust across sex, age, and ethnic groups. Both inconclusive fibrosis and fibrosis were strongly associated with malignancy of the liver or bile ducts [(HR = 1.41; 1.21-1.66) and (HR = 5.66; 4.19-7.64), respectively].

Liver fibrosis score is independently associated with malignancy occurrence and certain types of malignancies, and may serve as an indicator of high-risk cancer in the general population.

Post-hepatectomy liver failure (PHLF) is one of the major complications following hepatectomy for hepatocellular carcinoma (HCC). Early identification and precise prediction of PHLF are essential for effective management. This study aimed to evaluate the predictive value of intra-hepatectomy indocyanine green retention rate at 15 min (ICGR15) for the remnant liver for grade B/C PHLF in HCC patients undergoing hemi-hepatectomy.

This prospective study recruited 31 HCC patients who underwent hemi-hepatectomy. ICGR15 was measured at three time points: pre-hepatectomy, intra-hepatectomy (for the remnant liver), and post-hepatectomy. The primary endpoint was the occurrence of grade B/C PHLF according to ISGLS criteria. Logistic regression analysis was employed to evaluate the predictive performance of each parameter and to conduct risk assessment. The XGBoost algorithm was utilized to compare the predictive values of various parameters by calculating the mean Shap values.

Among the study participants, 25.8% (8 patients) developed grade B/C PHLF. The intra-hepatectomy ICGR15 for remnant liver exhibited the highest predictive accuracy for grade B/C PHLF, with a ROC-AUC of 0.864 and a PR-AUC of 0.791. The optimal threshold for ICGR15-intra was established at 19.8%. Patients with ICGR15-intra value of 19.8% or higher were found at significantly increased risk of grade B/C PHLF (OR[95% CI] = 3.602[1.437-6.750], P value = 0.004), and experienced a higher incidence of severe post-hepatectomy complications.

Intra-hepatectomy ICGR15 for the remnant liver was an important predictor of grade B/C PHLF in patients undergoing hemi-hepatectomy for HCC. An intra-hepatectomy ICGR15 threshold of 19.8% might effectively identify patients at high risk of developing grade B/C PHLF and severe post-hepatectomy complications, helping surgeons' final decision-making on the table.

Metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosis and management have evolved rapidly alongside the increasing prevalence of obesity and related complications. Hepatology has expanded its focus beyond late-stage cirrhosis and portal hypertension to earlier, complex MASLD cases in younger patients, necessitating closer collaboration with endocrinology. The renaming of nonalcoholic fatty liver disease (NAFLD) to MASLD reflects its pathophysiology, reduces stigma, and has prompted new research directions. Noninvasive tests such as liver stiffness measurement now play a crucial role in diagnosis, reducing reliance on invasive liver biopsies. However, advanced omics technologies, despite their potential to enhance diagnostic precision and patient stratification, remain underutilized in routine clinical practice. Behavioral factors, including posttraumatic stress disorder (PTSD) and lifestyle choices, influence disease outcomes and must be integrated into patient management strategies. Primary care settings are critical for early screening to prevent progression to advanced disease, yet sizable challenges remain in implementing effective screening protocols. This Review explores these evolving aspects of MASLD diagnosis and management, emphasizing the need for improved diagnostic tools, multidisciplinary collaboration, and holistic care approaches to address existing gaps and ensure comprehensive patient care across all healthcare levels.

Metabolic dysfunction-associated steatohepatitis (MASH) is associated with a >10-fold increase in liver-related mortality. However, biomarkers predicting both MASH and mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are missing. We developed a metabolome-derived prediction score for MASH and examined whether it predicts mortality in Chinese and European cohorts.

The MASH prediction score was developed using a multi-step machine learning strategy, based on 44 clinical parameters and 250 serum metabolites measured by proton nuclear magnetic resonance in 311 Chinese adults undergoing a liver biopsy. External validation was conducted in a Finnish liver biopsy cohort (n = 305). We investigated associations of the score with all-cause and cause-specific mortality in the population-based Shanghai Changfeng study (n = 5,893) and the UK biobank (n = 111,673).

A total of 24 clinical parameters and 194 serum metabolites were significantly associated with MASH in the Chinese liver biopsy cohort. The final MASH score included BMI, aspartate aminotransferase, tyrosine, and the phospholipid-to-total lipid ratio in VLDL. The score identified patients with MASH with AUROCs of 0.87 (95% CI 0.83-0.91) and 0.81 (95% CI 0.75-0.88) in the Chinese and Finnish cohorts, with high negative predictive values. Participants with a high or intermediate risk of MASH based on the score had a markedly higher risk of MASLD-related mortality than those with a low risk in Chinese (hazard ratio 23.19; 95% CI 4.80-111.97) and European (hazard ratio 20.15; 95% CI 10.95-37.11) individuals after 7.2 and 12.6 years of follow-up, respectively. The MASH prediction score was superior to the Fibrosis-4 index and the NAFLD fibrosis score in predicting MASLD-related mortality.

The metabolome-derived MASH prediction score accurately predicts risk of MASH and MASLD-related mortality in both Chinese and European individuals.

Metabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related death. However, biomarkers predicting not only MASH, but also death due to liver disease, are missing. We established a MASH prediction score based on 44 clinical parameters and 250 serum metabolites using a machine learning strategy. This metabolome-derived MASH prediction score could accurately identify patients with MASH among both Chinese and Finnish individuals, and it was superior to the Fibrosis-4 index and the NAFLD fibrosis score in predicting MASLD-related death in the general population. Thus, the new MASH prediction score is a useful tool for identifying individuals with a markedly increased risk of serious liver-related outcomes among at-risk and general populations.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), encompasses a spectrum of liver diseases characterized by hepatic steatosis, the presence of at least one cardiometabolic risk factor, and no other apparent cause. Metabolic syndrome (MetS) is a cluster of clinical conditions associated with increased risk of cardiovascular disease, type 2 diabetes, and overall morbidity and mortality. This narrative review summarizes the changes in the management of people with MetS and NAFLD/MASLD from screening to therapeutic strategies that have occurred in the last decades. Specifically, we underline the clinical importance of considering the different impacts of simple steatosis and advanced fibrosis and provide an up-to-date overview on non-invasive diagnostic tests (i.e., imaging and serum biomarkers), which now offer acceptable accuracy and are globally more accessible. Early detection of MetS and MASLD is a top priority as it allows for timely interventions, primarily through lifestyle modification. The liver and cardiovascular benefits of a global and multidimensional approach are not negligible. Therefore, a holistic approach to both conditions, MetS and related chronic liver disease, should be applied to improve overall health and longevity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a critical health concern, with metabolic dysfunction-associated steatohepatitis (MASH) representing a severe subtype that poses significant risks. This study aims to develop a robust diagnostic model for high-risk MASH utilizing a multi-omics approach.

We initiated proteomic analysis to select differential proteins, followed by liver transcriptional profiling to localize these proteins. An intersection of differential proteins and liver-expressed genes facilitated the identification of candidate biomarkers. Subsequently, scRNA-seq data helped ascertain the subcellular localization of these biomarkers in kupffer cells. We then established two MASLD models to investigate the co-localization of F4/80 and the target proteins in Kupffer cells using immunofluorescence dual-labeling. Correlation analyses were performed using blood samples from a discovery cohort of 144 individuals with liver pathology to validate the relationships between candidate biomarkers and MASLD phenotypes. Using LASSO regression, we established the ABD-LTyG predictive model for high-risk MASH (NAS ≥ 4 + F ≥ 2) and validated its efficacy in an independent cohort of 171 individuals. Finally, we compared this model against three classic non-invasive liver fibrosis diagnostic methods.

A proteo-transcriptomic comparison identified 58 consistent biomarkers in plasma and liver, with 25 closely associated with MASLD phenotype. Utilizing single-cell data and the HPA database, we delineated the localization of these biomarkers in liver cells, identifying TREM2, IL18BP, and LGALS3BP predominantly in the Kupffer cell subpopulation. Validation in animal models confirmed elevated expression and cellular localization of TREM2, IL18BP, and LGALS3BP in MASLD. To enhance diagnostic capability, we integrated clinical characteristics using LASSO regression to develop the ABD-LTyG model, comprising AST, BMI, total bilirubin (TB), vitamin D, TyG, and the biomarkers LGALS3BP and TREM2. This model demonstrated an AUC of 0.832 (95% CI 0.753-0.911) in the discovery cohort and 0.807 (95% CI 0.742-0.872) in the validation cohort for diagnosing high-risk MASH, outperforming traditional assessments such as FIB-4, NFS, and APRI.

The integration of circulating biomarkers and clinical parameters into the ABD-LTyG model offers a promising approach for diagnosing high-risk MASH. This study underscores the importance of multi-omics strategies in enhancing diagnostic accuracy and guiding clinical decision-making.

Metabolic associated fatty liver disease (MAFLD) is now a leading cause for chronic liver disease worldwide. Bariatric surgery has a beneficial effect on morbid obesity. We aimed at evaluating the impact of sleeve gastrectomy on the course of metabolic associated fatty liver disease.

An observational prospective cohort study from February 2021 to March 2023 included 66 morbidly obese patients diagnosed with MAFLD. Sleeve gastrectomy was done, where intra-operative liver biopsy was obtained. Baseline values of anthropometric measures, full metabolic profile and liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) using the XL probe were compared with three and six-months post-operatively.

Prevalence of MAFLD was histologically diagnosed in 75%. There was a significant decrease in body mass index, circumference, systolic and diastolic blood pressures in the low-density lipoprotein (LDL), triglycerides (TG), cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), LSM by transient elastography measurements in kilo Pascals (TE-kPa) and CAP level from baseline to three and six months post-operatively. Also, the AST/platelets ratio (APRI), NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4) and atheroscelerosis cardiovascular risk score (ASCVD) scores decreased significantly from baseline to six months of follow-up. In MAFLD patients, there was a significant positive linear correlation between the CAP score and TE, between the CAP and AST, ALT, ASCVD score, but a negative correlation with high density lipoprotein (HDL). Also, there was a significant positive correlation between the percentage of decline TE and APRI scores and percentage of decline of CAP, glycated hemoglobin (HbA1c) and homeostasis model assessment for insulin resistance (HOMA-IR).

There was a very high prevalence of steatosis and steatohepatitis in asymptomatic morbidly obese patients. Sleeve gastrectomy has a beneficial effect on MAFLD and its associated comorbidities.

Noninvasive tests (NITs), such as platelet-based indices and ultrasound/MRI elastography, are widely used to assess liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). However, platelet counts are not routinely included in Japanese health check-ups, limiting their utility in large-scale screenings. Additionally, elastography, while effective, is costly and less accessible in routine practice. Most existing AI-based models incorporate these markers, restricting their applicability. This study aimed to develop a simple yet accurate AI model for liver fibrosis staging using only routine demographic and biochemical markers.

This retrospective study analyzed biopsy-proven data from 463 Japanese MASLD patients. Patients were randomly assigned to training (N = 370, 80%) and test (N = 93, 20%) cohorts. The AI model incorporated age, sex, BMI, diabetes, hypertension, hyperlipidemia, and routine blood markers (AST, ALT, γ-GTP, HbA1c, glucose, triglycerides, cholesterol).

The Support Vector Machine model demonstrated high diagnostic performance, with an area under the curve (AUC) of 0.886 for detecting significant fibrosis (≥ F2). The AUCs for advanced fibrosis (≥ F3) and cirrhosis (F4) were 0.882 and 0.916, respectively. Compared to FIB-4, APRI, and FAST score (0.80-0.96), SVM achieved comparable accuracy while eliminating the need for platelet count or elastography.

This AI model accurately assesses liver fibrosis in MASLD patients without requiring platelet count or elastography. Its simplicity, cost-effectiveness, and strong diagnostic performance make it well-suited for large-scale health screenings and routine clinical use.

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.

This study aimed to investigate the conceivable utility of the aspartate aminotransferase to platelet ratio index (APRI) in prognostic prediction for patients with cardiogenic shock (CS) hospitalized in the intensive care unit (ICU).

Data for patients diagnosed with CS were obtained from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and categorized into groups based on the APRI quartiles. The primary endpoint encompassed in-hospital and ICU mortality rates. The secondary outcomes included sepsis and acute kidney injury (AKI). Kaplan-Meier survival analysis was utilized to assess differences in main endpoints among groups categorized by their APRI.

This study collected data from 1808 patients diagnosed with CS. Multivariate Cox regression analysis indicated that an elevated APRI was independently correlated with a heightened risk of in-hospital mortality (hazard ratio (HR) 1.005 [95% confidence interval (CI) 1.003-1.007]; p < 0.001) and ICU mortality (HR 1.005 [95% CI 1.003-1.007]; p < 0.001). Multivariate logistic regression analysis demonstrated that APRI was independently correlated with a heightened risk of sepsis (odds ratio (OR) 1.106 [95% CI 1.070-1.144]; p < 0.001) and AKI (OR 1.054 [95% CI 1.035-1.073]; p < 0.001).

An increased APRI was linked to worse clinical outcomes in critically ill patients with cirrhosis. Nevertheless, further extensive prospective investigations are needed to validate these findings.

This study investigated the consistency of the FIB-4, APRI, and GPR indices in assessing significant liver fibrosis and cirrhosis in patients with Coronavirus Disease 2019(COVID-19) who also suffer from various liver diseases, providing references for the clinical selection and application for non-invasive assessment methods.

The study evaluated 744 COVID-19 patients with coexisting liver diseases: 508 cases with non-alcoholic fatty liver disease (NAFLD), 158 cases with chronic hepatitis B (CHB), and 78 cases with a combination of both ailments. FIB-4, APRI, and GPR were employed to assess significant liver fibrosis and cirrhosis. Concordance among the methods was determined using Kappa analysis, and receiver operating characteristic (ROC) curves helped identify the optimal cutoff values for each index.

For COVID-19 patients with NAFLD, Kappa values for significant liver fibrosis were 0.81, 0.90, 0.80, and 0.79, and for cirrhosis, they were 0.88, 0.97,0.88, and 0.88, respectively (all p < 0.05). Among those with CHB, Kappa values were 0.81, 0.81, 0.83, and 0.75 for fibrosis, and0.87, 0.91, 0.88, and 0.92 for cirrhosis (all p < 0.05). In patients with coexisting liver diseases, the values were 0.87, 0.86, 0.86, and 0.78 for fibrosis, and 0.67, 0.69, 0.54, and 0.81for cirrhosis (all p < 0.05). Linear trend analysis revealed significant relationships between FIB-4 values, APRI values, GPR values, and the severity of COVID-19 (χ2 trend: 15.205,35.114, and 13.973, respectively, all p < 0.001), between FIB-4 values and APRI values and the coronavirus negative conversion time (all p < 0.05) in COVID-19 with NAFLD, and between FIB-4 values and GPR values and the coronavirus negative conversion time in patients with COVID-19 with CHB(all p < 0.05).

Using the current cutoff values, the non-invasive assessments demonstrated almost perfect consistency in evaluating significant liver fibrosis and cirrhosis in COVID-19 patients with liver diseases, though FIB-4 and GPR showed moderate consistency in cirrhosis evaluation in patients with coexisting liver conditions. Moreover, it also indicated that increased liver fibrosis correlates with more severe COVID-19 and prolonged coronavirus negative conversion time.

The global prevalence of non-alcoholic steatohepatitis (NASH) and its associated risk of adverse outcomes, particularly in patients with advanced liver fibrosis, underscores the importance of early and accurate diagnosis.

To develop a machine learning-based diagnostic model for advanced liver fibrosis in NASH patients.

A total of 749 patients who underwent liver biopsy at Beijing Ditan Hospital, Capital Medical University, between January 2010 and January 2020 were included. Patients were randomly divided into training (n = 522) and validation (n = 224) cohorts. Five machine learning models were applied to predict advanced liver fibrosis, with feature selection based on Shapley Additive Explanations (SHAP). The diagnostic performance of these models was compared to traditional scores such as the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4), using metrics including the area under the receiver operating characteristic curve (AUROC), decision curve analysis (DCA), and calibration curves.

The Extreme Gradient Boosting (XGBoost) model outperformed all other machine learning models, achieving an AUROC of 0.934 (95%CI: 0.914-0.955) in the training cohort and 0.917 (95%CI: 0.880-0.953) in the validation cohort (P < 0.001). Incorporating liver stiffness measurement into the model further improved its performance, with an AUROC of 0.977 (95%CI: 0.966-0.980) in the training cohort and 0.970 (95%CI: 0.950-0.990) in the validation cohort, significantly surpassing APRI and FIB-4 scores (P < 0.001). The XGBoost model also demonstrated superior clinical utility, as evidenced by DCA and calibration curve analysis in both cohorts.

The XGBoost model provides a highly accurate, non-invasive diagnosis of advanced liver fibrosis in NASH patients, outperforming traditional methods. An online tool based on this model has been developed to assist clinicians in evaluating the risk of advanced liver fibrosis.

The Hep-Net position paper comes at a significant time in the history of Metabolically Associated Fatty Liver Disease (MAFLD) due to the rapid rise in this disease entity in the past decade. Metabolically Associated Fatty Liver Disease, by its very name, encompasses several common metabolic disease entities, top among those being diabetes and obesity. For Pakistan, the situation is serious as it is among the top 10 countries globally regarding the prevalence of obesity and number one in terms of diabetes, with over a quarter of adults affected. There remains slight ambiguity as regards the nomenclature of MAFLD, with western societies preferring to remove the word "fatty" and substitute with `'steatotic" i.e. MASLD. Regardless of names/titles the metabolic nature of the disease and its management remains the same and fortunately, that is something where universal consensus is present. Under the umbrella of Hep-Net, eminent hepatologists from all over Pakistan have pooled their efforts to formulate guidelines that are specifically tailored to the Pakistani population, its specific lifestyle and relevant interventions that are needed to treat fatty/steatotic liver disease. By virtue of its multi-systemic consequences, metabolic fatty liver disease represents the most significant and expensive disease entity, globally. Prevention, through public education and timely intervention in diagnosed cases will serve to avert a healthcare storm that will far outweigh viral hepatitis.

Liver fibrosis progression is influenced by older age and cardiometabolic risk factors such as obesity and is associated with an increased risk of cardiovascular events. While statins may protect against cardiovascular complications, their effects in elderly individuals with obesity and liver fibrosis are unclear.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) database was used to evaluate the effect of pravastatin on major adverse cardiovascular events in an elderly population (>70 years). Subjects were categorized by BMI: lean (<25 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). Liver fibrosis was assessed using the FIB-4 index: low risk (<2.0), intermediate risk (2.0-2.66) and high risk (≥2.67). Time-to-event data were analysed using the Cox proportional hazards model, adjusted for confounders and compared the placebo and pravastatin groups.

A total of 5.804 subjects were included. In the placebo group, the highest risk group (high FIB-4 and obesity) had a significantly higher hazard ratio for (non-)fatal stroke (HR 2.74; 95% CI 1.19-6.29) compared to the low FIB-4, lean BMI group. This risk disappeared in the same pravastatin group. Pravastatin did not affect other cardiovascular endpoints. All-cause mortality was significantly higher in subjects with lean weight and high FIB-4 on placebo (HR 1.88; 95% CI 1.14-3.11), but not on pravastatin (HR .58; 95% CI .28-1.20).

Elderly individuals with obesity and liver fibrosis are at higher risk for (non-)fatal stroke, which is reduced with pravastatin. Pravastatin also potentially lowers all-cause mortality in subjects with lean weight and liver fibrosis.

Noninvasive tests (NITs) are used in all aspects of liver disease management. Their most prominent break-through since the millennium has been in advancing early detection of liver fibrosis, but their use is not limited to this. In contrast to the symptom-driven assessment of decompensation in patients with cirrhosis, NITs provide not only opportunities for earlier diagnoses but also accurate prognostication, targeted treatment decisions, and a means of monitoring disease. NITs can inform disease management and decision-making based on validated cutoffs and standardized interpretations as a valuable supplement to clinical acumen. The Baveno VI and VII consensus meetings resulted in tangible improvements to pathways of care for patients with compensated and decompensated advanced chronic liver disease, including the combination of platelet count and transient elastography to diagnose clinically significant portal hypertension. Furthermore, circulating NITs will play increasingly important roles in assessing the response to interventions against ascites, variceal bleeding, HE, acute kidney injury, and infections. However, due to NITs' wide availability, there is a risk of inaccurate use, leading to a waste of resources and flawed decisions. In this review, we describe the uses and pitfalls of NITs for hepatic decompensation, from risk stratification in primary care to treatment decisions in outpatient clinics, as well as for the in-hospital management of patients with acute-on-chronic liver failure. We summarize which NITs to use when, for what indications, and how to maximize the potential of NITs for improved patient management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been linked with sepsis outcomes. However, the immune mechanisms by which MASLD aggravates sepsis severity are unknown. This prospective cohort study aimed to analyze serum cytokine and chemokine kinetics in patients with MASLD and community-acquired sepsis. Out of the 124 patients, 68 (55%) were diagnosed with MASLD. There were no differences in age, sex, comorbidities, baseline sepsis severity, or etiology between the groups. Serum concentrations of 27 cytokines and chemokines on admission and day 5 of hospitalization were analyzed using a multiplex bead-based assay. Patients with MASLD had significantly higher serum concentrations of IL17A, IL-23, IL-33, CXCL10 and TGF-β1. Different cytokine kinetics were observed; patients with MASLD had a decrease in IL-10, IL-23, CXCL10 and TGF-β1, and an increase in IL-33, CXCL5 and CXCL1 on day 5. In the non-MASLD group, there was a decrease in IFN-γ, IL-6, IL-23 and CCL20, and an increase in CCL11 and CXCL5. While TGF-β1 significantly increased in non-MASLD, in MASLD, it decreased on day 5. Kinetics of TGF- β1 and CCL11 were associated with mortality in patients with MASLD. In conclusion, MASLD is linked with distinct cytokine and chemokine profiles during sepsis.

Background and Objectives: Fatty Liver Disease is a major health problem worldwide. We can distinguish liver steatosis as non-associated or associated with chronic/acute alcohol consumption. These two entities share similar stages ranging from hepatic fat storage (namely, steatosis) to inflammation, necrosis, and fibrosis until hepatocellular carcinoma (HCC). Over time, "Metabolic Associated Fatty Liver Disease" (MAFLD) has replaced nonalcoholic fatty liver disease (NAFLD) nomenclature and has included cardiometabolic criteria in these patients definition. Thus, obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia are MAFLD features and are of the metabolic syndrome. Importantly, there is not a specific treatment for MAFLD, but there are therapeutic strategies that act on metabolic dysfunction related to MAFLD. They can reduce the progression of liver fibrosis and its complications. Materials and Methods: For all these reasons, we conducted a narrative review of the literature, and we focused on metabolic dysfunction related to MAFLD, with a special regard for cholesterol metabolism. Results: MAFLD is a recently redefined condition that better describes the metabolism derangement responsible for fatty liver disease. This distinguishes MAFLD from NAFLD. In fact, the diagnostic criteria for MAFLD require the presence of liver steatosis together with at least one of the following: obesity, T2DM, or evidence of metabolic disorder such as hypertriglyceridemia, low high-density lipoprotein cholesterol, or hypertension. As a result, MAFLD is closely linked to an increased cardiometabolic risk. Current therapeutic approaches can be used to reduce this risk, focusing on lifestyle interventions and pharmacological strategies. Several treatments in patients diagnosed with MAFLD are mainly cholesterol-lowering remedies. Among these, Pro-protein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) show the most promising efficacy profile but data on liver fibrosis are lacking. Agonists of GLP-1 receptor, Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and Dipeptidyl Peptidase-4 inhibitors (DPP-4i) have a " multi-hit " action allowing their use also in diabetic patients with MAFLD. Conclusions: Lifestyle modifications, some nutraceuticals, statins, incretins, and PCSK9i have changed the natural course and significantly improved the cardiometabolic outcomes of MAFLD. Emerging cholesterol-lowering drugs, such as Bempedoic acid, can overcome low compliance to statins' use and their controversial effect on liver fibrosis. Finally, medications targeting insulin resistance allow for strategic interventions of the convoluted pathophysiology of MAFLD in multiple steps, with the potential to reduce liver steatosis, inflammation, and necrosis and, sometimes even to reverse liver fibrosis.

This review highlights the impact of weight loss on metabolic dysfunction associated steatotic liver disease (MASLD), formally known as nonalcoholic fatty liver disease (NAFLD), and its progressive form of metabolic dysfunction associated steatohepatitis (MASH), formally known as nonalcoholic steatohepatitis (NASH). The effects of weight loss, as achieved through lifestyle modification, pharmacotherapy, bariatric surgery or endobariatric procedures on MASLD/MASH and hepatic fibrosis are discussed.

Although foundational in the treatment of MASLD/MASH, weight loss through life-style modification is challenging for most patients to achieve and sustain long-term. In patients with MASLD/MASH, a multidisciplinary approach may facilitate success with lifestyle modification, individualized consideration of pharmacotherapies and/or surgical approaches that have potential to lend an improvement in MASLD/MASH. Effective and sustained weight loss improves hepatic steatosis, steatohepatitis and potentially hepatic fibrosis. Improvement in hepatic fibrosis can improve patient-related outcomes associated with complications of advanced hepatic fibrosis or cirrhosis in patients with MASLD/MASH. Identifying risk factors that influence MASLD/MASH and early implementation of therapeutic weight loss strategies may improve chronic liver injury and decrease risk for adverse clinical outcomes related to progressive hepatic fibrosis attributable to MASLD/MASH.

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

There are no known non-invasive tests (NITs) designed for accurately detecting metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis stages F2-F3, excluding cirrhosis-the FDA-defined range for prescribing Resmetirom and other drugs in clinical trials. We aimed to validate and re-optimize known NITs, and most importantly to develop new machine learning (ML)-based NITs to accurately detect MASH F2-F3.

Clinical and metabolomic data were collected from 443 patients across three countries and two clinic types (metabolic surgery, gastroenterology/hepatology) covering the entire spectrum of biopsy-proven MASH, including cirrhosis and healthy controls. Three novel types of ML models were developed using a categorical gradient boosting machine pipeline under a classic 4:1 split and a secondary independent validation analysis. These were compared with twenty-three biomarker, imaging, and algorithm-based NITs with both known and re-optimized cutoffs for MASH F2-F3.

The NAFLD (Non-Alcoholic Fatty Liver Disease) Fibrosis Score (NFS) at a - 1.455 cutoff attained an area under the receiver operating characteristic curve (AUC) of 0.59, the highest sensitivity (90.9 %), and a negative predictive value (NPV) of 87.2 %. FIB-4 risk stratification followed by elastography (8 kPa) had the best specificity (86.9 %) and positive predictive value (PPV) (63.3 %), with an AUC of 0.57. NFS followed by elastography improved the PPV to 65.3 % and AUC to 0.62. Re-optimized FibroScan-AST (FAST) at a 0.22 cutoff had the highest PPV (69.1 %). ML models using aminotransferases, metabolic syndrome components, BMI, and 3-ureidopropionate achieved an AUC of 0.89, which further increased to 0.91 following hyperparameter optimization and the addition of alpha-ketoglutarate. These new ML models outperformed all other NITs and displayed accuracy, sensitivity, specificity, PPV, and NPV up to 91.2 %, 85.3 %, 97.0 %, 92.4 %, and 90.7 % respectively. The models were reproduced and validated in a secondary sensitivity analysis, that used one of the cohorts as feature selection/training, and the rest as independent validation, likewise outperforming all other applicable NITs.

We report for the first time the diagnostic characteristics of non-invasive, metabolomics-based biomarker models to detect MASH with fibrosis F2-F3 required for Resmetirom treatment and inclusion in ongoing phase-III trials. These models may be used alone or in combination with other NITs to accurately determine treatment eligibility.

To explore the correlation between serum Golgi protein 73 (GP73) levels and the degree of fibrosis in Metabolic dysfunction associated steatotic liver disease (MASLD); to establish a non-invasive diagnostic algorithm based on serum GP73 and liver elasticity.

This is a prospective cross-sectional study, including 228 patients diagnosed with MASLD from May 2018 to January 2024 at two tertiary hospitals. Clinical data and hepatic pathological features and the correlation between serum GP73 and liver fibrosis were assessed. A new algorithm was conducted after logistic regression. Receiver Operating Characteristic (ROC) curve was used to compare its diagnostic performance with traditional models.

Significant fibrosis was diagnosed in 37.2% (85/228) patients. Serum GP73 levels were markedly higher in patients with significant fibrosis than in those without (128 ng/mL v.s 46 ng/mL, p< 0.001). Serum GP73 levels independently predicted significant liver fibrosis (adjusted odds ratio, aOR 1.028, p< 0.001). A new algorithm based on GP73 was developed with a higher area under ROC (AUC) of 0.840 than that of Fibrosis index-4 (p< 0.001).

Serum GP73 is an independent risk factor for significant liver fibrosis in MASLD, and the GFA (GP73-Fibroscan-Age) model has good diagnostic efficacy for significant liver fibrosis.

Sequential or combined treatment with nucleos(t)ide analogs (NAs) and pegylated interferon alpha-2b (Peg-IFN-α-2b) can improve the clinical cure rate. However, its clinical application is limited due to the adverse reactions associated with IFN.

A multi-center prospective observational study was conducted involving 59 NAs-treated chronic hepatitis B (CHB) patients who were treated with a combination therapy of NAs and Peg-IFN-α-2b for 48 weeks. Another 327 NAs-treated patients received NAs monotherapy for 48 weeks. At the end of the treatment, patients were classified into either the clinically cured group or the non-clinically cured group based on clinical efficacy. The study aimed to analyze the clinical cure rate and the predictive factors.

After propensity score matching (PSM), a total of 104 patients were included in the exposure and the control groups. After 48 weeks of treatment, 13 patients in the exposed group achieved clinical cure, with a cure rate of 25%. In contrast, in the control group was 1.92%. The clinical cure rate was greater in the population with CHB or compensated cirrhosis treated with sequential or combined Peg-IFN-α-2b and NAs than in the control group (p < 0.001). Patients treated with Peg-IFN-α-2b were divided into a clinical cure group and a non-clinical cure group for single-factor regression and multi-factor binary logistic regression. The results showed that baseline qHBsAg [relative ratio (RR) = 0.997, 95%CI: [0.995, 0.999], p = 0.031] and △TBiL (RR = 0.698, 95%CI: [0.555, 0.879], p = 0.002) were independent influencing factors for achieving clinical cure in patients with CHB or compensated cirrhosis.

A lower baseline qHBsAg and decrease in TBiL at 24 weeks of treatment are independent influencing factors for achieving clinical cure. The lower the baseline qHBsAg and the higher the △TBiL levels after 24 weeks of treatment, the higher the probability of patients achieving clinical cure.

This study aimed to determine the burden of suspected nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in a predominantly Hispanic patient population and explore the utility of the American Gastroenterological Association's NAFLD Clinical Care Pathway (CCP).

Electronic medical records (n = 223) were used to divide patients into risk groups based on the amount of metabolic risk factors they presented, diabetic status, or if they presented other liver diseases. Fribosis-4 (FIB-4) scores were used to determine the risk for advanced fibrosis.

Most patients (83.8%) were considered at risk for NAFLD based on CCP criteria, and about a third of patients (33.2%) were found to be at indeterminate (n = 60; 26.9%) or high risk (n = 14; 6.3%) for advanced fibrosis. Most indeterminate-risk patients (78.3%) were not referred for liver imaging.

This study demonstrates the potential of the CCP as a corrective tool that could help to better identify and screen patients at risk for NAFLD.

The validity of non-invasive tests (NITs) of liver fibrosis for the prediction of liver and mortality outcomes in an Australian cohort is unknown. We aimed to verify the utility of available NITs to predict overall and cause-specific mortality and major adverse liver outcome (MALO).

This was an analysis from the Crossroads 1 clinic sub-study of a randomly sampled adult cohort from regional Australia between 2001 and 2003. Baseline variables included demographic details, anthropometry, health and lifestyle data, and laboratory tests. Non-alcoholic fatty liver disease (NAFLD) and metabolic-(dysfunction) associated fatty liver disease (MAFLD) were defined by fatty liver index ≥ 60 and other accepted criteria. Outcomes were defined by the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes for linked hospitalization and death registry data. Available serum-based NITs were analyzed as predictors of overall, cardiovascular disease-related, and cancer-related mortality and MALO in those with fatty liver disease (FLD).

In total, 1324 and 1444 participants were included for NAFLD and MAFLD analysis (prevalence 35.4% and 40.7%, respectively). There were 298 deaths (89 cardiovascular disease-related and 98 cancer-related) and 24 MALO over a median 19.7 years of follow-up time. In both forms of FLD, fibrosis-4 index, Steatosis-Associated Fibrosis Estimator score, and Forns fibrosis score consistently had the highest area under the receiver operating characteristic curve (AUROC) for overall and cause-specific mortality, with AUROC > 0.70 for each outcome. However, all had poor discriminatory ability for determining MALO in each FLD.

Several liver fibrosis NITs perform similarly reasonably well in predicting the risk of mortality outcomes in those with FLD but are poorly discriminatory for MALO prediction.

Fibrosis-4 (FIB-4) index is a widely used test for non-invasively assessing liver fibrosis. We aimed to investigate the association between FIB-4 index and risk of all-cause mortality in patients at high cardiovascular (CV) risk and to determine whether coexisting renal dysfunction mediates this association.

Single-center prospective study of 994 patients with established or suspected coronary artery disease undergoing coronary angiography, followed for a median of 44 months. Mortality data were obtained through the Italian Health Card Database. At baseline, the median FIB-4 index was greater in deceased vs. alive patients (1.71 vs. 1.38, p < 0.001) and in those with reduced eGFR than in those with normal eGFR (1.65 vs. 1.37, p < 0.001). For each unit increase in the baseline log-FIB-4 index, the risk of all-cause mortality sharply increased during the follow-up (hazard ratio [HR] 2.31, 95%CI 1.31-4.08, p = 0.004). Similarly, assuming the lowest baseline FIB-4 risk category as the reference, the risk of all-cause mortality progressively increased across the indeterminate (HR 1.82, 95%CI 1.18-2.82, p = 0.007) and the highest baseline FIB-4 risk categories (HR 2.33, 95%CI 1.37-3.97; p = 0.002). A causal mediation analysis showed that about one-third of the effect of FIB-4 index on mortality risk was mediated by reduced eGFR (32.8 %, p = 0.01).

Increased FIB-4 index predicts the long-term risk of all-cause mortality in patients at high CV risk, and this risk is, at least in part, mediated by reduced eGFR. Further prospective studies are needed to confirm these findings.

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.

The monocyte-to-Apolipoprotein A1 ratio (MAR) emerges as a potentially valuable inflammatory biomarker indicative of metabolic dysfunction-associated fatty liver disease (MASLD). Accordingly, this investigation primarily aims to assess the correlation between MAR and MASLD risk. A cohort comprising 957 individuals diagnosed with type 2 diabetes mellitus (T2DM) participated in this study. The relationship between MAR and MASLD was analyzed through binomial logistic regression analysis and restricted cubic splines (RCS). Furthermore, a comparative assessment of MAR and monocyte to high-density lipoprotein ratio (MHR) in identifying MASLD efficacy was conducted using receiver operating characteristic curve analysis. Remarkably, even after adjusting for metabolic parameters and hepatic functional markers, MAR stood out as an independent predictor for MASLD (OR 1.58, 95% CI 1.36-1.84; P < 0.001) and displayed a nonlinear positive association with MASLD risk according to RCS analysis (P for nonlinearity and overall < 0.001). Notably, MAR exhibited superior diagnostic accuracy for identifying MASLD compared to MHR (AUC: 0.772 vs 0.722, P < 0.001). In summary, MAR emerges as a promising inflammatory indicator for MASLD, demonstrating potential as a valuable screening tool to bolster the management of MASLD within the T2DM population.

As metabolic dysfunction-associated steatotic liver disease (MASLD) becomes more prevalent worldwide, it is imperative to create more accurate technologies that make it easy to assess the liver in a point-of-care setting. The aim of this study is to test the performance of a new software tool implemented in Velacur (Sonic Incytes), a liver stiffness and ultrasound attenuation measurement device, on patients with MASLD. This tool employs a deep learning-based method to detect and segment shear waves in the liver tissue for subsequent analysis to improve tissue characterization for patient diagnosis.

This new tool consists of a deep learning based algorithm, which was trained on 15,045 expert-segmented images from 103 patients, using a U-Net architecture. The algorithm was then tested on 4429 images from 36 volunteers and patients with MASLD. Test subjects were scanned at different clinics with different Velacur operators. Evaluation was performed on both individual images (image based) and averaged across all images collected from a patient (patient based). Ground truth was defined by expert segmentation of the shear waves within each image. For evaluation, sensitivity and specificity for correct wave detection in the image were calculated. For those images containing waves, the Dice coefficient was calculated. A prototype of the software tool was also implemented on Velacur and assessed by operators in real world settings.

The wave detection algorithm had a sensitivity of 81% and a specificity of 84%, with a Dice coefficient of 0.74 and 0.75 for image based and patient-based averages respectively. The implementation of this software tool as an overlay on the B-Mode ultrasound resulted in improved exam quality collected by operators.

The shear wave algorithm performed well on a test set of volunteers and patients with metabolic dysfunction-associated steatotic liver disease. The addition of this software tool, implemented on the Velacur system, improved the quality of the liver assessments performed in a real world, point of care setting.

Prediction models are increasingly being used to guide clinical decision making in primary care. There is a lack of evidence exploring the views of patients and general practitioners (GPs) in primary care around their use and implementation. We aimed to better understand the perspectives of GPs and people with lived experience of depression around the use of prediction models and communication of risk in primary care.

Qualitative methods were used. Data were generated over 6 months (April to October 2022) through semi-structured interviews with 23 people with lived experience of depression and 22 GPs. A multidisciplinary research team and Patient Advisory Group were involved throughout the study. Data were analysed inductively using thematic analysis.

GPs describe using prediction models in consultations only when the models are either perceived to be useful (e.g., because they help address an important clinical problem) or if GPs feel compelled to use them to meet financial or contractual targets. These two situations are not mutually exclusive, but if neither criterion is met, a model is unlikely to be used in practice. People with lived experience of depression and GPs reported that communication of model outputs should involve a combination of risk categories, numerical information and visualisations, with discussions being tailored to the individual patients involved. Risk prediction in a mental health context was perceived to be more challenging than for physical health conditions.

Clinical prediction models are used in practice but thought must be given at the study development stage to how results will be presented and discussed with patients. Meaningful, embedded public and patient involvement and engagement are recommended when developing or implementing clinical prediction models.

We used a combination of embedded consultation and collaboration/co-production in our approach to public and patient involvement in this study. A Patient Advisory Group made up of people with lived experience of depression were involved from study conception and contributed to study design, participant recruitment, interpretation of findings and dissemination (including in the preparation of this manuscript).

The relationships between alcohol consumption, cardiometabolic factors, and liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease and those with metabolic dysfunction and alcohol-associated liver disease remain unclear.

To investigate the longitudinal associations among alcohol consumption, cardiometabolic factors, and liver fibrosis in patients with these two liver diseases.

This observational cohort study included 1866 patients with metabolic dysfunction-associated steatotic liver disease and 521 patients with metabolic dysfunction and alcohol-associated liver disease who underwent > two health checkups over >2 years. The associations of both liver diseases with worsening non-invasive liver fibrosis scores were assessed using the Cox regression analysis.

Both liver diseases independently worsened liver fibrosis in both sexes. However, the hazard ratio for worsening liver fibrosis in females was significantly higher with metabolic dysfunction and alcohol-associated liver disease than with metabolic dysfunction-associated steatotic liver disease. Worsening liver fibrosis was not associated with alcohol consumption. Among males with metabolic dysfunction-associated steatotic liver disease, the hazard ratio for worsening liver fibrosis was significantly higher in those with multiple cardiometabolic factors compared to those with a single cardiometabolic factor.

Although both metabolic steatotic liver disease and metabolic alcohol-associated liver disease were correlated with liver fibrosis progression in both sexes, the impact of alcohol consumption and cardiometabolic factors on fibrosis progression differed by sex. Cardiometabolic factors may have a stronger impact on liver fibrosis than alcohol consumption in males with metabolic dysfunction-associated steatotic liver disease.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) help manage type 2 diabetes (T2DM) and may have efficacy in steatotic liver disease. Objective: To determine the prevalence and clinical impact of GLP-1 RA use in patients with T2DM and liver disease. Methods: This was a retrospective study of adult patients with T2DM and nonalcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL), or nonalcoholic steatohepatitis (NASH) between 1/1/21-12/31/21. Patients with hepatitis B or C, or on pioglitazone were excluded. Eligible patients treated with a GLP-1 RA were compared to controls. The primary outcome was change in Fibrosis-4 (FIB-4) score, with NAFLD Fibrosis Score (NFS) as a secondary outcome. Follow-up scores were calculated from labs within 3 to 15 months after baseline. Results: Of 242 eligible patients, 79 patients (32.6%) were treated with a GLP-1 RA. At baseline, FIB-4 score was lower and NFS was higher in the GLP-1 RA group vs controls (1.80 vs 2.33; P = .101, .36 vs -.47, P < .001; respectively). At follow up, FIB-4 score decreased to 1.77 in the GLP-1 RA group and increased to 2.71 in controls (P = .045). Follow up NFS was stable in the GLP-1 RA group and increased in the control group (.36 vs -.43; P = .308). Conclusion: Patients treated with GLP-1 RAs had less evidence of liver fibrosis progression compared to no treatment, although the differences were small. These results suggest that treatment with GLP-1 RAs may have clinical impact on slowing liver fibrosis, however results should be confirmed in a larger, more diverse sample.

Participants with cardiovascular diseases (CVD) often exhibit liver function abnormalities, hepatic fibrosis and cirrhosis. The extent of liver fibrosis is closely related to the prognosis of CVD. However, the association between the liver fibrosis-8 (FIB-8) index, a marker of liver fibrosis, and all-cause mortality in CVD participants remains unclear. This study aims to investigate the relationship between the FIB-8 index and all-cause mortality among individuals with CVD.

A total of 1727 CVD American participants were enrolled from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. Initially, we constructed weighted COX regression models and performed sensitivity analyses to examine the correlation between the FIB-8 index and all-cause mortality in CVD participants. Subsequently, we employed restricted cubic spline (RCS) to visualize their linear relationship. Finally, the stratified analyses and interaction tests of covariates were performed and presented in the forest plot.

A total of 1727 participants were included in our study, with a mean age of 61.68 ± 0.47 years, with men accounting for 59.19%. After adjustment for relevant covariables, weighted COX regression models indicated that the hazard ratio (HR) and 95% confidence interval (95% CI) for the association between the FIB-8 index and all-cause mortality in CVD participants was 1.21 (1.12, 1.30). Sensitivity analysis was then conducted, revealing that the results remained stable. In fully adjusted model, individuals in quartiles 3 and 4 demonstrated significant statistical differences compared to the lowest FIB-8 index quartile, with HR (95% CI) values of 1.88 (1.23, 2.87) and 2.17 (1.33, 3.53), respectively. Subsequently, RCS showed a linear relationship between the FIB-8 index and all-cause mortality among CVD participants. Finally, the interaction test revealed that no other covariables had significant interactions with the FIB-8 index in this study.

A positive and linear correlation was observed between the FIB-8 index and all-cause mortality among CVD adult participants in NHANES from 1999 to 2018. Our findings indicated that the FIB-8 index could serve as an excellent indicator for assessing all-cause mortality within the CVD population. The lower the FIB-8 index, the lower the all-cause mortality among CVD participants.

Background and Aims: Multiple non-invasive tests (NITs) for identifying advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are available, but, due to the limitations of single NITs, the American Association for the Study of Liver Disease (AASLD) guidelines suggest a two-step strategy, combining the Fibrosis-4 Index (FIB-4) score with the Enhanced Liver Fibrosis (ELF) test to improve diagnostic accuracy and minimize unnecessary liver biopsies. However, few real-world studies have used such a sequential approach. We here evaluated the diagnostic accuracy of the ELF test in patients with recently established metabolic dysfunction-associated steatotic liver disease (MASLD) and assessed the clinical utility of applying a two-step strategy, including the ELF test following the FIB-4 score assessment, in patients with MASLD. Methods: We enrolled 153 patients diagnosed with MASLD who underwent liver biopsy at the Dong-A University Hospital between June 2018 and August 2023. The degree of fibrosis was determined based on liver biopsy results. Various NITs were used, including the Aminotransferase-to-Platelet Ratio Index (APRI), FIB-4 score, NAFLD Fibrosis score (NFS) and ELF test. The diagnostic efficacy of these NITs was evaluated based on the area under the receiver operating characteristic curve (AUROC). Additionally, the performance of each test was further examined both when applied individually and in a two-step approach, where FIB-4 was used followed by ELF testing. Key metrics such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were used for this analysis. Results: Overall, 153 patients with MASLD (mean age: 46.62 years; 52.3% men; 28.1% with type 2 diabetes) were included. The performance of the NITs in identifying advanced fibrosis was as follows: the AUROC of the APRI, FIB-4, NFS, and ELF tests were 0.803 (95% confidence interval (CI), 0.713-0.863), 0.769 (95% CI, 0.694-0.833), 0.699 (95% CI, 0.528-0.796), and 0.829 (95% CI, 0.760-0.885), respectively. The combination of the FIB-4 score ≥ 1.30 and the ELF score ≥ 9.8 showed 67.86% sensitivity, 90.40% specificity, a PPV of 75.18%, an NPV of 86.78%, an accuracy of 83.64%, and an AUROC of 0.791 for predicting the diagnosis of advanced fibrosis. This approach excluded 28 patients (71.8%) from unnecessary liver biopsies. Conclusions: Our study demonstrated that ELF testing maintained diagnostic accuracy in assessing liver fibrosis in patients with MASLD in real-world practice. This test was used as a second step in the evaluation, reducing clinically unnecessary invasive liver biopsies and referrals to tertiary institutions. This approach allows assessment of MASLD severity in primary care settings without requiring additional equipment.

MicroRNAs (miRNAs) can act as biomarkers and descriptors of the association between infections and other diseases, such as hepatitis and COVID-19. This study aims to investigate the role of miRNA serum expression according to laboratory data concerning hepatitis and COVID-19. Seventy individuals recruited in Southern and Southeastern Brazil donated serum samples and were divided into four groups: (i) 20 negative subjects, (ii) 20 presenting hepatitis, (iii) 19 with COVID-19 and (iv) 11 with hepatitis and COVID-19. Three miRNAs (miR-122, miR-143 and miR-223) were evaluated using real-time PCR. Hematological and biochemical markers were also analyzed. MiR-143 and miR-223 were downregulated among the hepatitis/COVID-19 group (p < 0.05). A positive correlation was observed between miR-223 and lymphocytes. There was a negative correlation between alanine transaminase (ALT) and aspartate transaminase (AST) for miR-143 and miR-223 and gamma-glutamyl transferase (GGT), alkaline phosphatase (AP) and neutrophil/lymphocyte ratio (NLR) only for miR-223 (p < 0.05). For hepatic fibrosis (FIB-4), miR-122 and miR-143 had a greater association and miR-223 was more associated with a history of vaccination against COVID-19. MicroRNAs 143 and 223 could be useful as biomarkers for hepatitis coinfection with COVID-19.

Hepatocellular carcinoma (HCC) is typically detected only at advanced stages when treatment options are limited. Most of the current HCC risk models focus on patients with viral hepatitis or diagnosed cirrhosis or require variables not routinely available in clinical care.

To identify modifiable HCC risk factors in the general population and to develop a risk score to inform HCC screening and risk-factor modification interventions for high-risk individuals without viral hepatitis or decompensated cirrhosis.

This cohort study analyzed demographic, clinical, laboratory, and diagnostic data from the US Department of Veterans Affairs (VA) electronic health records. Data were divided into development and validation samples. Veterans aged 30 to 95 years were included, and those with hepatitis B or C virus infection, hepatic decompensation, or prevalent HCC were excluded. Patients were followed up until the occurrence of HCC diagnosis, death, or December 31, 2021. A Cox proportional hazards regression model for 10-year risk of HCC was developed and used to create an HCC risk score, and performance in development and validation samples and in patient subgroups was evaluated. One outpatient visit date per person at least 18 months after VA entry, between October 1, 2007, and March 31, 2020, was randomly selected and used as the index date for the start of follow-up. Analyses were performed from March 2023 to May 2024.

Age, sex, race and ethnicity, body mass index, liver fibrosis (detected with Fibrosis-4 Index [FIB-4]), diabetes status, smoking status, and alcohol use.

First HCC diagnosis during follow-up. This information was ascertained from VA national cancer registry topography and histology codes and from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for the inpatient or outpatient visits.

This study of 6 509 288 veterans included 6 048 917 males (92.9%), with a median (IQR) age of 65 (54-74) years, who identified as being of Hispanic (5.3%), non-Hispanic Black (15.0%), non-Hispanic White (68.9%), or other (4.6%) race and ethnicity. Overall, 15 142 patients (0.2%) developed HCC, 69.5% of whom had FIB-4 of 3.25 or lower at baseline. While FIB-4 was the most important variable, age, sex, race and ethnicity, body mass index, diabetes, smoking, and alcohol use were also informative. Discrimination in the development sample was better than FIB-4 alone (C statistic, 0.83 [95% CI, 0.82-0.85] vs 0.79 [95% CI, 0.77-0.80]). The HCC risk score performed consistently well in the validation sample and in all subgroups. A FIB-4 threshold of 3.25 would screen 5.0% of the cohort at a cost of 28 false-positives for every true-positive; a model risk score of 58 would screen 4.7% of the cohort at a cost of 23 false-positives for every true-positive.

Results of this study suggest that a multivariable risk score that uses routinely available clinical data outperforms FIB-4 alone in identifying patients at risk of HCC who do not have viral hepatitis or hepatic decompensation at baseline.