Non-alcoholic fatty liver disease (NAFLD) affects more than a quarter of the global population and has become the world's number one chronic liver disease, seriously jeopardizing public life and health. Despite the new terminology of metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed, the mechanisms underlying the heterogeneity across BMI stratification in non-alcoholic fatty liver disease (NAFLD) remain unclear. The aim of this study was to reveal the differences in metabolic and fibrotic characteristics between lean (BMI < 23 kg/m2) and non-lean NAFLD in an Asian population.

The current study collected NAFLD patients from the physical examination population. Patients were divided into two groups by BMI to compare their clinical parameters, including lean (BMI < 23 kg/m2) and non-lean (BMI ≥ 23 kg/m2) and fibrosis subgroups (with a threshold of LSM = 8 kPa) and analyzed for risk factors by logistic regression models.

Of the 11,577 NAFLD patients who participated in the study, there were 916 lean and 10,661 non-lean. The non-lean group was younger than the lean group (median age 50 vs. 52 years, P < 0.001) and had a significantly higher prevalence of hypertension (28.0% vs. 18.3%), diabetes mellitus (10.1% vs. 6.1%), and liver fibrosis (9.1% vs. 5.1%) (all P < 0.001). Analysis of metabolic indexes showed that TyG, TyG-BMI, TG/HDL-C and APRI were higher in the non-lean group (all P < 0.001). Gender stratification revealed that ALT was significantly higher in the male non-lean group, while HDL-C was lower in the female non-lean group (1.35 vs. 1.47 mmol/L). Multiple regression suggested that the risk of fibrosis was independently associated with CAP values and fasting glucose, BMI, direct bilirubin, globulin, and age in the non-lean group, whereas the risk was mainly driven by GGT and ALP in the lean group.

Non-lean NAFLD patients showed more significant metabolic disturbances and risk of liver fibrosis. Although metabolic indicators (TyG, FIB-4) have limited predictive value for liver fibrosis, they are strongly associated with metabolic risk in MASLD.

Mexican-origin adults have one of the highest rates of metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form metabolic dysfunction steatohepatitis (MASH) in the US. Given the costs and invasiveness of liver biopsy, this study assessed the application of Hepatoscope® 2DTE, the latest-generation transient elastography for liver stiffness in Mexican adult immigrants from Southern Arizona and compared it with FibroScan® VCTE™.

Participants (n = 199) from a cross-sectional community-based study completed anthropometric measures, demographic information, a blood draw, and liver stiffness measurements (LSM) with FibroScan VCTE and the ultraportable Hepatoscope 2DTE. LSM2DTE and LSMVCTE were compared using Spearman's correlation and Bland-Altman analysis. The number of at-risk for fibrosis participants as assessed using each system was compared according to FIB-4.

A total of 122 participants were considered for this sub-analysis which consisted of 71.3 % women. Mean age was 51.9 ± 12.1 years, BMI was 30.7 ± 5.7 kg/m², 43.4 % of participants had obesity, and 19.7 % were diabetic. Mean FIB-4 was 1.00 ± 0.53, and median LSM were 5.6 [4.7 - 6.7] and 5.3 [4.1 - 5.8] kPa for 2DTE and VCTE, respectively. 2DTE significantly correlated with VCTE (r = 0.53, p < 0.0001) and there was no systematic bias between the two LSM. There was no difference in the number of at-risk for fibrosis participants between the two LSM per FIB-4 categories.

Hepatoscope can be used for point-of-care liver stiffness assessment and risk stratification of adults at risk of liver fibrosis in community-based settings.

There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes mellitus (T2DM) versus those without T2DM in biopsy-proven metabolic dysfunction-associated steatotic liver disease. We examined LSM progression in participants with T2DM versus those without T2DM in a large, prospective, multicenter cohort study.

This study included 1231 adult participants (62% female) with biopsy-proven metabolic dysfunction-associated steatotic liver disease who had VCTEs at least 1 year apart. LSM progression and regression were defined by a ≥20% increase and an upward or downward change, respectively, in the LSM category in the Baveno VII categories for compensated advanced chronic liver disease, compared between participants with T2DM (n = 680) versus no T2DM (n = 551) at baseline. The mean (±SD) age and body mass index were 51.8 (±12.0) years and 34.0 (±6.5) kg/m 2 , respectively. The median (IQR) time between the first and last VCTE measurements was 4.1 (2.5-6.5) years. Participants with T2DM had higher LSM progression at 4 years (12% vs. 10%), 6 years (23% vs. 16%), and 8 years (50% vs. 39%), p = 0.04. Using a multivariable Cox proportional hazards model adjusted for multiple confounders, the presence of T2DM remained an independent predictor of LSM progression (adjusted HR: 1.35, 95% CI: 1.01-1.81, p = 0.04). T2DM was not associated with LSM regression ( p = 0.71). Mean HbA1c was significantly associated with LSM progression ( p = 0.003) and regression ( p = 0.02).

Using serial VCTE data from a multicenter study of participants with biopsy-proven metabolic dysfunction-associated steatotic liver disease, we demonstrate that T2DM and HbA1c are associated with LSM progression.

Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome (MetS), type-2 diabetes mellitus and atherosclerosis. A high prevalence of steatosis and advanced liver fibrosis has been described in psoriasis. The influence of MetS and its compounds, patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 gene polymorphisms and the cumulative dose of methotrexate (MTX) in the progression of steatotic disease are still under debate. A suitable new classification for psoriasis-related liver disease, under the umbrella of steatotic liver disease (SLD), might be evaluated due to the potential impact of MTX on liver steatosis. Considering the interplay between the MetS, steatosis and MTX, a new definition for this complex disease might be discussed since it is not entirely addressed under the umbrella of SLD and metabolic-dysfunction associated SLD. Hence, shortly, a discussion could be raised on the feasible term "Met-Drug SLD", metabolic and drug-induced SLD, which comprises both metabolic dysfunction and drug-related SLD. This review aims to report the best evidence to accurately classify liver disease in psoriasis, considering the new definition of SLD, allowing appropriate management once it is carefully defined.

Hepatocellular carcinoma (HCC), a common consequence of chronic liver disease, ranks among the most prevalent cancers globally and contributes significantly to cancer-related mortality. Liver fibrosis is intimately associated with hepatic function and the likelihood of future HCC occurrence. Despite the fact that liver biopsy continues to be the gold standard for diagnosing fibrosis, its utility is hindered by cost and invasiveness, along with patient unease, procedural rejection, and potential adverse effects. Liver elastography has become a leading noninvasive means of assessing tissue stiffness with considerable diagnostic precision. Malignant tumors generally exhibit higher cellularity in comparison to benign ones, resulting in increased stiffness. Elastography techniques capitalize on alterations in tissue elasticity stemming from specific pathological or physiological processes. Technological innovations, such as advanced ultrasound imaging and artificial intelligence (AI)-integrated systems, are paving the way for enhanced diagnostic accuracy and risk prediction. Recent research underscores the potential of elastography in managing HCC patients, presenting novel clinical applications, including prediction of HCC development, differentiation between malignant and benign liver lesions, evaluating treatment response, and forecasting recurrence post-treatment, though certain findings remain contentious. Therefore, this review aims to sum up the latest advancements in liver elastography for HCC patients, outlining its applications while addressing existing limitations and avenues for future progress.

Background/Objectives: We aim to determine if cytokeratin-18 fragment (CK-18F) could be used to diagnose metabolic dysfunction-associated steatohepatitis (MASH). Methods: A total of 289 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled in the analysis. To evaluate the association between CK-18F levels and the histological features of MASH, weighted receiver operating characteristic (ROC) curve analyses were performed. The diagnostic utility of CK-18F was compared with that of the Mac-2 binding protein glycan isomer (M2BPGi). Additionally, we assessed the predictive performance of combining CK-18F with either the FIB-4 index or the FIB-3 index for diagnosing MASH and investigated predictors of future progression to cirrhosis. Results: CK-18F was more useful for MASH diagnosis than M2BPGi and the FIB-4 index in the multivariate analysis, with a sensitivity of 47% and specificity of 80% at a CK-18F cutoff value of 750 U/L. Because CK-18F decreases with advanced liver fibrosis, the combination of the FIB-4 or FIB-3 index with CK-18F was examined to identify cases with cirrhosis. The combination of the CK-18F level and the FIB-3 index better predicted MASH than the combination of the CK-18F level and the FIB-4 index. The FIB-3 index was the most useful predictor of cirrhosis on imaging five years after diagnosis with F2 or less disease. Conclusions: CK-18F is useful for MASH diagnosis, and the diagnostic algorithm combining CK-18F with the FIB-3 index may be more useful than the previously reported MASH diagnostic algorithm that combined it with the FIB-4 index.

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.

Although Emerging evidence suggests the association of environmental factors with hepatic steatosis and fibrosis, the relationship between Cobalt exposure and hepatic steatosis and fibrosis was not clear.

Our study was aimed to explore the association between blood Cobalt level and hepatic steatosis and advanced liver fibrosis diagnosed by vibration controlled transient elastography (VCTE) in US adults.

This study analyzed data from 3193 individuals participating in the 2017-2018 National Health and Nutrition Examination Surveys. Participants were classified into four groups according to the quartiles of blood cobalt concentration. Liver stiffness and fat content were assessed through vibration-controlled transient elastography (VCTE), including measurements of the controlled attenuation parameter (CAP). The association between blood cobalt levels and the prevalence of hepatic steatosis and advanced liver fibrosis was explored using logistic regression models and stratified subgroup analyses.

The CAP values showed a significant decline across increasing cobalt quartiles. Participants in the highest quartile had a 41 % lower risk of hepatic steatosis compared to those in the lowest quartile (odds ratio: 0.59, 95 % confidence interval: 0.46-0.76, p < 0.001). However, no significant association existed between blood Cobalt and advanced liver fibrosis. Subgroup analysis revealed that the relationship was consistent across age, gender and body mass index subgroups.

This study showed that blood Cobalt level was negatively association with hepatic steatosis. This may be due to increased development from hepatic steatosis to advanced liver fibrosis upon Cobalt exposure.

In a rapidly changing technology landscape, "Clinical Decision Support" (CDS) has become an important tool to improve patient management. CDS systems offer medical professionals new insights to improve diagnostic accuracy, therapy planning, and personalized treatment. In addition, CDS systems provide cost-effective options to augment conventional screening for secondary prevention. This review aims to (i) describe the purpose and mechanisms of CDS systems, (ii) discuss different entities of algorithms, (iii) highlight quality features, and (iv) discuss challenges and limitations of CDS in clinical practice. Furthermore, we (v) describe contemporary algorithms in oncology, acute care, cardiology, and nephrology. In particular, we consolidate research on algorithms across diseases that imply a significant disease and economic burden, such as lung cancer, colorectal cancer, hepatocellular cancer, coronary artery disease, traumatic brain injury, sepsis, and chronic kidney disease.

Sarcopenic obesity (SO) is associated with adverse outcomes in diseased patients. This study aimed to examine the prevalence and risks associated with SO, with a focus on the impact of SO on cardiovascular risk in patients with MASLD.

In this cross-sectional study, patients with MASLD were prospectively enrolled. Through dual-energy X-ray absorptiometry (DXA) scans, their body compositions were analyzed to identify who had SO and osteopenia/osteoporosis. The primary aim is to investigate risks associated with SO, followed by analyzing the association between SO and cardiovascular disease (CVD).

Two hundred and twenty-three patients with MASLD were enrolled. The prevalence of SO was 47.1%, respectively. Patients coexisted with MASLD and SO had increased visceral adipose tissue (VAT), higher fatty liver index (FLI) and fibrosis 4 (FIB-4) score. Regression analysis revealed higher FLI and FIB-4 score, as well as history of hypertension, were risks associated with SO. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score was higher in patients coexisted with MASLD and SO compared to those without (10.1% vs. 7.3%, p = 0.006). Regression analysis showed that increased VAT and FIB-4 score were associated with raised risk of ASCVD.

Prevalence of SO in MASLD patients is considerable. The presence of SO also linked to higher risk of ASCVD. Therefore, the recognition of SO in patients with MASLD is important in clinical care.

The non-HDL-C to HDL-C ratio (NHHR) is a dependable lipid marker linked to atherosclerotic traits. This study examines the potential relationship between NHHR and both metabolic dysfunction-associated steatotic liver disease (MASLD) and advanced liver fibrosis.

This study investigated the relationship between NHHR levels and both MASLD and advanced liver fibrosis using data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) in the United States. First, we conducted a baseline characteristics analysis of the population based on NHHR quartiles. Second, we employed multivariable weighted linear regression models to examine the associations between NHHR and MASLD, as well as advanced liver fibrosis. Third, we utilized restricted cubic splines (RCS) to assess potential non-linear relationships. Fourth, we performed subgroup analyses. Finally, ROC curve analysis was conducted to evaluate the effectiveness of NHHR.

In the main analysis, this study included a total of 9,864 participants. Following multivariable logistic regression and comprehensive adjustments, elevated NHHR levels in the Q3 and Q4 groups were significantly linked to MASLD, with odds ratios of 1.59 (95% CI: 1.20-2.11) and 1.83 (95% CI: 1.40-2.39), respectively (P for trend < 0.0001). Elevated NHHR levels in the Q2 and Q3 groups remained significantly linked to a decreased risk of advanced liver fibrosis, with odds ratios of 0.61 (95% CI 0.40-0.94, P = 0.03) and 0.64 (95% CI 0.47-0.89, P = 0.01), respectively. RCS analysis revealed a U-shaped nonlinear association between NHHR and both MASLD (P = 0.000; P for nonlinear = 0.029) and advanced liver fibrosis (P = 0.0001; P for nonlinear = 0.000). In the subgroup analysis, we found that this relationship was significant only in certain subgroups. The ROC curve analysis revealed that NHHR exhibited the best predictive performance for diagnosing MASLD based on the fatty liver index (FLI). The optimal cutoff point for NHHR in predicting MASLD using FLI was determined to be 2.476, with sensitivity and specificity values of 0.589 and 0.698, respectively.

NHHR may serve as a predictive marker for MASLD and advanced liver fibrosis, highlighting its potential significance in risk assessment and prevention strategies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an umbrella term for simple hepatic steatosis and the more severe metabolic dysfunction-associated steatohepatitis. The current reliance on liver biopsy for diagnosis and a lack of validated biomarkers are major factors contributing to the overall burden of MASLD. This study investigates the association between biomarkers and hepatic steatosis and stiffness measurements, measured by FibroScan®.

Data from the National Health and Nutritional Examination Survey (2017-2020) was collected for 15,560 patients. Propensity score matching balanced the data with a 1:1 case-to-control for age and sex allowing for preliminary trend assessment. Random Forest machine learning determined variable importance for the incorporation of key biomarkers (age, sex, race, BMI, HbA1C, PFG, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, ALT, AST, ALP, albumin, GGT, LDH, iron, total bilirubin, total protein, uric acid, BUN, and hs-CRP) into logistic regression models predicting steatosis (MASLD indicated by a controlled attenuation parameter™ score of >238 dB/m) and stiffness (hepatic fibrosis indicated by a median liver stiffness >7 kPa). Sensitivity analysis using XGBoost and Recursive Feature Elimination was performed.

The Random Forest models (the most accurate) predicted MASLD with 79.59% accuracy (p<0.001) and specificity of 84.65% and, hepatic fibrosis with 86.07% accuracy (p<0.001) and sensitivity of 98.01%. Both the steatosis and stiffness models identified statistically significant biomarkers, with age, BMI, and insulin appearing significant to both.

These findings indicate that assessing a variety of biomarkers, across demographic, metabolic, lipid, and standard biochemistry categories, may provide valuable initial insights for diagnosing patients for MASLD and hepatic fibrosis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a key risk factor for cardiovascular disease (CVD), potentially driven by shared metabolic mechanisms. Metabolic perturbations associated with MASLD and CVD remain underexplored in people with HIV (PWH).

We used data from the longitudinal multicenter 2000HIV study comprising 1895 virally suppressed PWH, out of which 970 had available liver and carotid artery measurements. Transient elastography with controlled attenuation parameter (CAP) was performed for the assessment of liver steatosis (CAP > 263 dB/m) and fibrosis (LSM ≥ 7.0). Historic and future incident CVD within 2-year follow-up, defined as myocardial infarction, stroke, peripheral arterial disease, and angina pectoris, were extracted from the medical files, while atherosclerotic plaque(s) in the carotid arteries were assessed using ultrasonography. Metabolic perturbations were analyzed using mass spectrometry-based untargeted metabolomics (n = 500 metabolites) and nuclear magnetic resonance spectroscopy for targeted lipids and other metabolites (n = 246 metabolites).

PWH with liver steatosis were more likely to have arterial plaques (47% vs. 36%; P value = 0.003) and CVD history (11% vs. 6.8%; P value = 0.021) than PWH without liver steatosis. These associations were only significant in lean PWH, in contrast to those with BMI ≥ 25 kg/m2. Metabolic pathways associated with liver steatosis and fibrosis primarily involved lipid and amino acid metabolism, and they were validated by targeted lipoproteomic measurements. Interestingly, metabolomic pathways and lipoproteomic signatures associated with MASLD were mostly distinct from those associated with CVD parameters. However, several metabolic pathways were shared, especially in lean PWH. These include arachidonic acid metabolism and formation of prostaglandin, purine metabolism, cholecalciferol metabolism, and glycine, serine, alanine, and threonine metabolism.

Metabolic disturbances linked to liver steatosis and CVD diverge across BMI categories in PWH. Lean PWH, unlike their overweight/obese counterparts, show common metabolic perturbations between MASLD and CVD, particularly involving arachidonic acid metabolism. This suggests that lean PWH with liver steatosis may face a heightened risk of CVD due to shared metabolic pathways, potentially opening avenues for targeted interventions, such as aspirin therapy, to mitigate this risk.

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.

Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F).

A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults.

LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

The treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) has focused on the control of comorbidities. Silybum marianum (SM) and alpha-lipoic acid (ALA) have shown antioxidant and adjuvant effects on the control of metabolic disorders.

To evaluate whether the SM-ALA formulation (LUDLEV®), in combination with the Mediterranean diet (MD), could improve MASLD-related liver injury.

A randomized, double-blind clinical trial was conducted on patients with MASLD. Administration of SM-ALA plus MD (group A) vs placebo plus MD (group B) was compared for 24 weeks. At baseline and weeks 12 and 24, anthropometric measurements, metabolic parameters, and liver function were analyzed. Clinical effectiveness was evaluated through transient elastography.

Fifty patients aged 54 ± 10 years were included, and the majority (74%) were female. Reduced visceral fat and umbilical circumference were reported in both groups, with significance in group A (P = 0.045 and 0.003, respectively). The decrease in controlled attenuation parameter was gradual and maintained at 12 and 24 weeks in group A (P = 0.026), whereas in group B the decrease was greater at week 12 and remained unchanged at week 24 (∆controlled attenuation parameter: -27 dB/m). Mild adverse effects were reported in 4 patients in group A (16%) and 4 patients in group B (16%), with no significant differences between groups (P = 0.641).

SM-ALA (LUDLEV®) combined with the MD can promote the improvement of metabolic parameters, reducing visceral fat and hepatic steatosis in Mexican patients with MASLD.

To investigate the effect of obesity on the stages of fibrosis discordance between FibroScan and liver biopsy.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of liver disease worldwide. Accurate fibrosis assessment is essential in MASLD patients for prognosis and treatment. Vibration-controlled transient elastography using FibroScan can overestimate liver fibrosis in obese patients.

This retrospective study included 245 MASLD patients who underwent FibroScan and liver biopsy. Participants were included with FibroScan controlled attenuation parameter (CAP) 250+, 10 liver stiffness measurements (LSM) with IQR/med ≤30%, and 10+ portal tracts on biopsy. Discordance was defined as a ≥2 stage difference between FibroScan and liver biopsy. Participants were stratified by BMI and obesity class to assess their association with discordance. We conducted a post hoc analysis to determine the implication of discordance on resmetirom eligibility. Data was entered into SPSS v28.

Among 245 patients, 29.4% exhibited a ≥2 stage discordance between FibroScan and biopsy. Class 3 obesity was significantly associated with discordance (38.6%) compared with class 2 obesity (24.6%) and class 0 to 1 obesity (18.4%). FibroScan suggested cirrhosis in 66 (57.9%) participants with class 3 obesity, however, liver biopsy confirmed cirrhosis in only 16 (24.2%) subjects and identified 28 (42.4%) subjects with stages 2 to 3 fibrosis, making them potentially eligible for resmetirom.

FibroScan significantly overestimates advanced fibrosis and cirrhosis in class 3 obesity. A second noninvasive test is warranted for accurate liver-directed therapeutic allocation and to minimize unnecessary biopsies in MASLD management.

Abundant research indicates that increased extracellular matrix (ECM) stiffness significantly enhances the malignant characteristics of hepatocellular carcinoma (HCC) cells. Plectin, an essential cytoskeletal linker protein, has recently emerged as a promoter of cancer progression, particularly in the context of cancer cell invasion and metastasis. However, the responsiveness of plectin to changes in ECM stiffness and its impact on HCC progression remain unclear. In this study, we aimed to investigate whether plectin responds to variations in ECM stiffness and to explore its involved molecular mechanisms in regulating HCC cell migration.

Our results showed that, when compared with control group (7 kPa), high ECM stiffness (53 kPa) boosts HCC cell migration by upregulating plectin and integrin β1 expression and increasing F-actin polymerization. Knockdown of integrin β1 negated the high stiffness-upregulated plectin expression. Furthermore, reducing either plectin or integrin β1 levels, or using latrunculin A, effectively prevented the high ECM stiffness-induced F-actin polymerization and HCC cell migration.

These findings demonstrate that integrin β1-plectin-F-actin axis is necessary for high matrix stiffness-driven migration of HCC cells, and provide evidence for the critical role of plectin in mechanotransduction in HCC cells.

With the availability of free antiretroviral therapy (ART) across India, HIV in adults has become a chronic disease with prolonged survival. The emergence of various non-communicable diseases in these prolonged survivors is a cause of concern. Metabolic dysfunction-associated steatotic liver disease (MASLD) in adults with HIV infection in India has not been explored to date. In this study, we attempted to assess the existence of MASLD in thirty adults registered at the Centre of Excellence in ART Care at a tertiary teaching hospital in New Delhi. This center provides free first-line, second-line, and third-line ART to patients as well as comprehensive HIV care including counseling, nutritional advice, and inpatient admissions for intercurrent illnesses. A total of 30 subjects were enrolled in the study to assess the occurrence of MASLD among people living with HIV (PLHIV) and its risk factors and to assess hepatic fibrosis in the subjects with MASLD using transient elastography and clinical fibrosis scores. The study population included 13 subjects on ART (43.3%) and 17 ART-naïve subjects (56.6%). All the study subjects underwent ultrasonography (USG) for the identification of the development of MASLD in them. Steatosis was identified as an increase in the echogenicity of the liver seen as an increase in the hepatorenal contrast and was further graded into the 3 grades of fatty liver. Out of the 30 subjects, 16.6% (5 out of 30) were found to have MASLD on USG, with grade 1 fatty changes seen in 4 (13.3%) and grade 2 fatty changes seen in 1 out of 30 subjects (3.3%). A majority (40%) of the subjects were underweight (body mass index [BMI] < 18.5). 22.7% of the male subjects included in the study had MASLD whereas none of the females had fatty changes in the liver on USG. Out of the study subjects, MASLD was detected in 17.6% of ART-naïve subjects while it was detected in 15.4% of subjects on ART. Although no statistically significant association was seen with any of these parameters, a few important trends were observed. These might be statistically significant in a higher power study with a larger sample size. Higher BMI (mean difference [MD] = 3.25, P = .09), waist circumference (MD = 3.84, P = .15), hip circumference (MD = 4.36, P = .14), and older age (MD = 6.56, P = .07) were observed to be associated with MASLD in our study, whereas the biochemical parameters and HIV-related factors were not seen to have any particular trend of association in our study. However, a higher median CD4 count was associated with MASLD as compared to the group without fatty changes on USG. On FibroScan, all 5 subjects with fatty changes in our study were found to have liver stiffness less than 7 kPa which corresponds to F0-F1 stage of fibrosis. Using the nonalcoholic fatty liver disease score, 2 subjects had scores corresponding to F0-F2 stage of fibrosis (as per METAVIR score) while the rest (3 out of 5) had indeterminate values. While on FIB4 scoring, 4 subjects had scores suggesting stage 0-1 fibrosis while 1 had a score suggestive of stage 4-6 fibrosis as per Ishak Fibrosis staging. As PLHIV with known diabetes mellitus, obesity, and hypothyroidism were excluded from our study, the prevalence of MASLD observed in our study underestimates the real prevalence of MASLD in this specific population. No significant association was observed between ART status or ART regimen and MASLD in our study subjects. However, in light of the existing evidence of association of dolutegravir (DTG) with significant weight gain, and the recent inclusion of DTG in the first-line ART regimen nationally in India, robust surveillance and large-scale studies are recommended to study the contribution of DTG to MASLD in PLHIV, if any.

FibroTouch® has shown efficacy in staging hepatic fibrosis in patients with chronic viral hepatitis B, but its performance in assessing liver steatosis and fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients remains understudied. We aimed to evaluate the diagnostic performance of FibroTouch® in assessing steatosis and fibrosis in the MASLD population.

Liver stiffness measurements and steatosis were assessed using FibroTouch® and FibroScan®, with FibroScan® as the reference standard. Pearson's correlation test evaluated correlations, and kappa statistics determined agreement between the two methods. Optimal cut-off values of FibroTouch® for predicting hepatic steatosis and fibrosis stages were determined through ROC curve analysis with the Youden index method.

Strong correlations were observed between FibroTouch® UAP and FibroScan® CAP (rho=0.74) and LSM values (rho=0.87) (p < 0.001 for both) in a total of 380 patients. The mean CAP value for the entire cohort was 285 ± 51 dB/m, and the median LSM for the cohort was 5 .3kPa. The optimal FibroTouch® UAP cutoffs were 229 dB/m for S0 vs. S1, 267 dB/m for S1 vs. S2, and 294 dB/m for S2 vs. S3. For FibroTouch® LSM, the optimal cutoffs were 6.0 kPa for F0-F1 vs. F2, 7.9 kPa for F2 vs. F3, and 10.6 kPa for F3 vs. F4. Moreover, FibroTouch® effectively assessed hepatic steatosis and fibrosis in patients with different BMIs.

FibroTouch® proved valuable in assessing hepatic steatosis and liver fibrosis staging in MASLD patients, enhancing its applicability in various clinical settings as a suitable and convenient option for MASLD patients.

Enhanced liver fibrosis (ELF) score is a noninvasive assessment for liver fibrosis. We aimed to evaluate the performance of changes in ELF score 3 years apart in combination with liver stiffness measurement (LSM)-hepatocellular carcinoma (HCC) score to predict HCC in chronic hepatitis B (CHB) patients. This is a prospective cohort study. Patients who underwent transient elastography (TE) examinations and at intermediate or high risk of HCC defined by LSM-HCC score were invited to repeat the examination about 3 years later. Their serum samples at these two time points were retrieved to assess the ELF score changes. The primary endpoint was HCC. There were 445 CHB patients (males: 73.9%; mean age: 51.6 ± 10.3 years) who received two TE examinations and ELF scores. Among them, 252 (56.6%) and 193 (43.4%) patients were at intermediate and high HCC risk at first assessment defined by LSM-HCC score, respectively. Kaplan-Meier analysis showed that the changes in ELF score could stratify the HCC risk in both intermediate- and high-risk patients defined by LSM-HCC score (p < 0.001 for intermediate-risk group; p = 0.011 for high-risk group). Patients remained having mild or moderate fibrosis at both assessments had the lowest risk of HCC (4.0%), followed by patients with fibrosis regressed (11.3%; p = 0.014) during a mean follow-up of 163 months. Patients remained having or progressed to severe fibrosis were at highest risk of HCC (> 20%). Consistent findings were demonstrated in patients at both intermediate and high risk of HCC defined by LSM-HCC score. Dynamic changes in ELF score provided additional value to LSM-HCC score for stratifying HCC risk in CHB patients.

This study aimed to investigate the relationship between advanced lung cancer inflammation index (ALI) and non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis (AF).

A total of 5642 individuals from the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2020 were examined. Limited cubic spline regression model, and weighted logistic regression were employed to determine if ALI levels were related to the prevalence of NAFLD and AF. Additionally, a mediating analysis was conducted to investigate the role of lipid biomarkers, such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), in the effects of ALI on the prevalence of NAFLD and AF.

After adjusting for potential confounders, a significant positive association was found between ALI with NAFLD and AF prevalence. Compared with those in ALI Tertile 1, participants in Tertile 3 had higher odds of NAFLD prevalence (odds ratio [OR]: 3.16; 95% confidence interval [CI]: 2.52-3.97) and AF (OR: 3.17; 95% CI: 2.30-4.36). Participants in both Tertile 2 and Tertile 3 had lower odds of developing AF (P for trend = 0.005). Moreover, we discovered a nonlinear association between ALI and NAFLD. An inflection point of 74.25 for NAFLD was identified through a two-segment linear regression model. Moreover, TC and HDL-C levels mediated the association between ALI and NAFLD by 10.2% and 4.2%, respectively (both P < 0.001).

Our findings suggest that higher ALI levels are positively associated with an increased prevalence of NAFLD and AF, partly mediated by lipid biomarkers.

Liver fibrosis, a critical predictor of the prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD), is traditionally diagnosed via biopsy. Nevertheless, non-invasive alternatives, such as serum biomarkers, vibration-controlled transient elastography, and magnetic resonance elastography, have become prominent because of the limitations of biopsies. Serum biomarkers, such as fibrosis-4 index and NFS Score, are also used widely, offering reliable diagnostic performance for advanced fibrosis. Vibration-controlled transient elastography and shear wave elastography provide further non-invasive evaluations with high diagnostic accuracy, particularly for advanced fibrosis, but the results may be affected by factors such as obesity. Magnetic resonance elastography, with superior diagnostic accuracy and operator independence, is a promising method, but its high cost and limited availability restrict its widespread use. Emerging algorithms, such as NIS4, FAST, or MAST score, have strong potential in identifying high-risk metabolic dysfunction-associated steatohepatitis patients. The integration of multiple non-invasive methods can optimize diagnostic accuracy, reducing the need for invasive biopsies while identifying patients at risk of liver-related complications. Further research is needed to refine these diagnostic tools and improve accessibility.

Chronic liver disease is a significant public health issue worldwide, with the degree of liver fibrosis and its progression significantly influencing the treatment and prognosis. A liver biopsy is the standard diagnostic method, but it is invasive and presents various issues. Therefore, numerous non-invasive diagnostic methods have been developed. Serum markers are categorized into indirect markers, which reflect liver damage, inflammation, or functional changes, and direct markers, which measure the components released into the bloodstream during fibrosis. In addition, various kinds of formulas that combined direct/indirect markers and demographic variables were developed and validated with encouraging outcomes. Nevertheless, despite their convenience, serum indicators require cautious interpretation because they are affected by a number of factors. More research will be needed to determine if the clinical course of chronic liver disease under a disease-specific treatment could be monitored appropriately using serological markers.

Background: Vibration-Controlled Transient Elastography (VCTE) with FibroScan is a non-invasive, reliable diagnostic tool for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD), enabling early detection and management to prevent severe liver diseases. VCTE's ease and portability suit primary care, streamlining referrals, promoting lifestyle changes, reducing costs, and benefiting underserved communities. Methods: Studies on point-of-care VCTE were systematically reviewed, followed by meta-analysis using a random-effects model. Pooled proportions with 95% confidence intervals were reported, and heterogeneity was assessed using I2%. Results: A total of twenty studies from 14 countries, including 6159 patients, were analyzed, with three studies from France, two from the U.S., and four from China. The population had a slight male preponderance, with a mean age range of 35-73 years and a BMI range of 24.4-41.1%. The diagnostic accuracy for detecting any fibrosis (≥F1) was reported in four studies (n = 210) with an AUC of 0.74, sensitivity of 69.5%, and specificity of 70.6%. For significant fibrosis (≥F2), eight studies (n = 650) reported an AUC of 0.69, sensitivity of 81.7%, and specificity of 64.6%. Advanced fibrosis (≥F3) was evaluated in 10 studies (n = 619), with an AUC of 0.84, sensitivity of 88.1%, and specificity of 63.8%. Cirrhosis (F4) was assessed in nine studies (n = 533), with an AUC of 0.65, sensitivity of 87.5%, and specificity of 62.6%. Steatosis diagnoses across stages S1 to S3 showed increasing diagnostic accuracies, with AUCs of 0.85, 0.76, and 0.80, respectively. Probe type and BMI were significant covariates influencing diagnostic performance for both fibrosis and steatosis, while the percentage of male participants also showed significant associations. Conclusions: VCTE shows high diagnostic accuracy for fibrosis and steatosis in MASLD patients at the point of care. Future research should assess its implementation in fibroscan settings.

Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms.

We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort. Participants underwent transient elastography to assess liver steatosis (controlled attenuation parameter (CAP) ≥263 dB/m) and -fibrosis (liver stiffness measurement (LSM) ≥7.0 kPa). Plasma protein concentrations (n = 2367) (Olink® Explore Panel) were compared between PLHIV with vs. without liver steatosis and PLHIV with vs. without fibrosis. Enriched pathways (using GO, KEGG and Reactome libraries) and correlations with clinical characteristics were assessed, and analyses were stratified by BMI category. In addition, concentrations of 242 proteins were compared between individuals ("controls") with and without liver steatosis (ratio of methylene:methylene and water >5.6% on magnetic resonance spectroscopy) from a separate cohort (300-OB), all having a BMI >26 kg/m2.

Steatosis and fibrosis were associated with 67/2367 (2.2%) and 17/2367 (0.7%) differentially expressed proteins (DEP), respectively, enriched in mostly metabolic pathways. Immunoglobulin superfamily member 9 (IGSF9) was amongst the top DEP associated with both steatosis and fibrosis. Stratifying by BMI revealed 8/2367 DEP associated with steatosis in lean- and 12/2367 DEP in overweight/obese individuals, with two shared DEP (IGSF9 and GHR). Conversely, protein signatures of overweight/obese PLHIV (32/242 DEP) and overweight/obese HIV-uninfected individuals (32/242 DEP) exhibited substantial overlap with 16 shared DEP. Notably, DEP correlated with HIV characteristics in lean individuals but not in overweight/obese PLHIV.

Lean and overweight/obese PLHIV exhibit distinct proteomic signatures associated with liver steatosis, with the former being more strongly correlated with HIV-specific factors and ART. In addition, we identified a protein, IGSF9, strongly related to liver fibrosis and steatosis across BMI categories.

The 2000HIV study is funded by ViiV Healthcare.

Recent studies have suggested an association between H. pylori and metabolic dysfunction associated steatotic liver disease (MASLD). We aim to evaluate the association of H. pylori virulence genes with non-invasive markers of liver injury and fibrosis in MASLD subjects.

A total of 362 dyspeptic patients who underwent gastroscopy were selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), gastric biopsies, and H. pylori virulence genes (cagA, vacA) were evaluated.

A cohort comprised of 61 % women and 39 % men with a median age of 52 (40-60) years. MASLD was observed in 42 %, and H. pylori-positive in 45 %. No differences were observed regarding H. pylori status at co-morbid metabolic conditions. In MASLD cohort, H. pylori-positive was associated with higher AST, ALT, FIB-4 and LSM. Indeed, carriers of cagA/vacA-s1/m1-positive allelic combination were associated with higher AST, ALT, FIB-4 and LSM but not cagA/vacA-s1/m1-negative. The OR for high-risk of significant/advanced- fibrosis by VCTE (≥8 kPa) with H. pylori-positive was 2.56 (95 % CI, 1.2-5.75) and for cagA/vacA-s1/-m1-positive allelic carriers was 4.01 (95 % CI, 1.38-11.56), but non-significant association in cagA/vacA-s1/-m1-negative. After adjusting for age, gender, diabetes, BMI and hypertension the OR for VCTE ≥8 kPa with H. pylori-positive was 2.43 (95 % CI, 1.88-12.44), and cagA/vacA-s1/m1-positive allelic carriers was 4.06 (95 % CI, 1.22-14.49).

In our cohort of functional dyspepsia (FD) patients with MASLD, H. pylori was associated with non-invasive markers of liver injury and fibrosis. Carriers of cagA/vacA-s1/m1-positive allelic combination showed an independent risk of significant/advanced fibrosis by VCTE.

 This study aimed to evaluate the severity of liver fibrosis in chronic liver disease patients using aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), FibroScan, and the Child-Turcotte-Pugh (CTP) score. It emphasized assessing fibrosis progression toward cirrhosis (F4 stage) and exploring the correlation between non-invasive markers and the CTP score for liver function and prognosis.

This observational cross-sectional study was conducted over one calendar year in the Department of Medicine at Baba Raghav Das (BRD) Medical College, Gorakhpur, India. A total of 200 patients with chronic liver disease were selected. Fibrosis scores were calculated using FibroScan, APRI, and FIB-4, while the modified CTP score was determined for each participant. Pearson's correlation was used to assess relationships between variables, while logistic regression evaluated the association of non-invasive methods (APRI, FIB-4, FibroScan) with severe fibrosis (F4). Odds ratios (ORs), sensitivity, specificity, and AUC were calculated, and ROC curves visualized their discriminative ability. Statistical significance was defined as p < 0.05.

 The study revealed a predominance of advanced fibrosis (F4) in males (82.5%) and patients with ethanol-induced liver disease (84.6%). FIB-4 had the strongest predictive value for advanced fibrosis with an OR of 3.8 (95% CI: 3.0-4.5) and AUC of 0.743, followed by APRI with an OR of 2.5 (95% CI: 1.9-3.1) and AUC of 0.757. CTP showed the highest sensitivity (95.45%) but a lower AUC (0.697), indicating its clinical value in correlating fibrosis severity with liver dysfunction. Hemoglobin, platelets, and INR showed no significant correlation with fibrosis, while total bilirubin was elevated in advanced CTP classes. A moderate positive correlation (r = 0.481, p < 0.001) was observed between fibrosis scores and CTP, linking fibrosis severity with liver dysfunction. These findings emphasize FIB-4's superior predictive accuracy, while APRI and CTP remain valuable complementary tools for liver disease prognosis.

 In conclusion, FIB-4 is the most accurate for staging advanced fibrosis, while APRI excels in initial screening due to its higher sensitivity. FibroScan effectively assesses direct fibrosis, and the CTP score adds prognostic value, making these methods complementary for managing chronic liver diseases.

Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is recommended for risk stratification of patients with nonalcoholic fatty liver disease (NAFLD). More recently, AGILE3 + and AGILE4 have combined LSM with clinical parameters to identify patients with advanced fibrosis and cirrhosis, respectively. However, there are limited data on prognostic performance of these scores in key at-risk subgroups such as those with diabetes and obesity compared to LSM alone.

This is a retrospective cohort study including 1903 adult patients with NAFLD from tertiary care centers in the United States and Singapore undergoing VCTE between 2015 and 2022. Primary predictors were FAST, LSM, AGILE3 + , and AGILE4 scores and the primary outcome was liver-related events (LRE). Patients were further stratified by diabetes and obesity status. Prognostic performance was measured using the time-dependent area under the receiver operating characteristic curve (tAUC) at 5 years.

In total, 25 LRE occurred and the overall incidence rate of LRE was 4.4 per 1000 person-years. tAUC for predicting LRE in the overall group was significantly higher with AGILE3 + (0.94 [95% CI: 0.90-0.98]) and AGILE4 (0.94 [95% CI: 0.90-0.98]) compared to LSM (0.87 [95% CI: 0.80-0.94]) (p = 0.001 and 0.009, respectively) and FAST (0.73 [95% CI: 0.59-0.86]) (p < 0.001 for both). Similarly, tAUC was significantly higher in those with T2D for AGILE3 + compared to LSM (0.92 vs 0.86, respectively) (p = 0.015) and FAST (0.92 vs 0.73, respectively) (p = 0.008). Among people with obesity, tAUC was significantly higher for AGILE3 + compared to LSM (0.95 vs 0.89, respectively) (p = 0.005) and FAST (0.95 vs 0.76, respectively) (p = 0.0035). Though AGILE4 had a higher tAUC in these subgroups compared to LSM, it did not reach statistical significance.

AGILE3 + significantly outperforms LSM and FAST for predicting LRE in patients with NAFLD including in those with diabetes or obesity.

Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk in persons with HIV (PWH). The lipidomic and metabolomic alterations contributing to this risk are poorly understood. We aimed to characterize the advanced lipoprotein and targeted metabolomic profiles in PWH and assess if the presence and severity of MASLD influence these profiles.

This is a cross-sectional analysis of a prospectively enrolled multicenter cohort. PWH without alcohol abuse or known liver disease underwent vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Lipidomic and metabolomic profiling was undertaken with nuclear magnetic resonance (NMR) spectroscopy. Hepatic steatosis was defined as CAP ≥ 263 dB/m and clinically significant fibrosis (CSF) as LSM ≥ 8 kPa. Logistic regression models assessed associations between MASLD, CSF and lipidomic and metabolic parameters.

Of 190 participants (71% cisgender male, 96% on antiretroviral therapy), 58% had MASLD and 12% CSF. Mean (SD) age was 48.9 (12.1) years and body mass index (BMI) 29.9 (6.4) kg/m2. Compared to PWH without MASLD (controls), PWH with MASLD had lower HDL-C but higher total triglyceride, VLDL-C, branched-chain amino acids, GlycA, trimethylamine N-oxide levels, Lipoprotein-Insulin Resistance and Diabetes Risk Indices. There were no significant differences in these parameters between participants with MASLD with or without CSF. In a multivariable regression analysis, MASLD was independently associated with changes in most of these parameters after adjustment for age, gender, race/ethnicity, type 2 diabetes mellitus, BMI, and lipid lowering medications use.

MASLD in PWH is independently associated with altered advanced lipoprotein and targeted metabolic profiles, indicating a higher CVD risk in this population.

The multisociety consensus nomenclature has introduced steatotic liver disease (SLD) with diverse subclassifications, which are metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), alcohol-associated liver disease (ALD), specific etiology, and cryptogenic. We investigated their prevalence, as per the new definition, in individuals undergoing health check-ups. Additionally, we analyzed the distribution of Fibrosis-4 (FIB-4) index and vibration-controlled transient elastography (VCTE)-derived liver stiffness measurement (LSM) for MASLD.

In this cross-sectional study, 6530 subjects undergoing a health check-up in Japan were included. Conventional B-mode ultrasound was carried out on all 6530 subjects, and those with MASLD underwent VCTE.

The prevalence of SLD was 39.5%, comprising MASLD 28.7%, MetALD 8.6%, ALD 1.2%, specific etiology SLD 0.3%, and cryptogenic SLD 0.7%. Subjects with VCTE-derived LSM ≥8 kPa constituted 2.1% of MASLD. FIB-4 ≥1.3 showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value for diagnosing VCTE-derived LSM ≥8 kPa were 60.6%, 77.0%, 5.3%, and 98.9%, respectively. The referral rate to specialists was 23.8% using FIB-4 ≥1.30. "FIB-4 ≥1.3 in subjects <65 years and FIB-4 ≥2.0 in subjects ≥65 years" showed higher PPV (6.7%) and lower referral rate (17.1%) compared with FIB-4 ≥1.3, but the sensitivity (54.5%) did not show adequate diagnostic capability as a noninvasive test for diagnosing VCTE-derived LSM ≥8 kPa.

Acknowledging the selection bias in hepatology centers, we undertook this prospective health check-up study. Although the FIB-4 index proves to be a convenient marker, it might not perform well as a primary screening tool for liver fibrosis in the general population (UMIN Clinical Trials Registry No. UMIN000035188).

Despite the development of transient elastography (TE)-based Agile scores for diagnosing fibrotic burden in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), their applicability in predicting kidney outcomes remains unclear. We aimed to investigate the association between liver fibrotic burden, as assessed by Agile scores, and the risk of incident chronic kidney disease (CKD) in patients with MASLD.

A total of 3240 participants with MASLD but without pre-existing CKD who underwent TE between July 2006 and October 2018 were selected. The primary outcome was incident CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria (≥1+ on dipstick) on two consecutive measurements. The secondary outcome was a 25% decline in eGFR measured on two consecutive visits.

During a median follow-up of 3.6 years, 187 participants (5.8%) developed incident CKD. When stratified into three groups according to Agile 3+ scores, multivariable Cox models revealed that risk of incident CKD was 2.77-fold (95% confidence interval [CI], 1.89-4.07; p < 0.001) higher in the high-risk group (Agile 3+ >0.68), compared to the low-risk group (Agile 3+ <0.45). During a median follow-up of 3.4 years, the high-risk group had a 2.41-fold higher risk (95% CI, 1.86-3.12; p < 0.001) of experiencing the secondary outcome, compared to the low-risk group. Similar findings were observed for Agile 4 scores. Prediction testing revealed that Agile scores were better predictors of kidney outcomes, compared to liver stiffness measured by TE.

In patients with MASLD, but without CKD, advanced liver fibrosis measured by Agile scores was significantly associated with a higher risk of incident CKD.

Intestinal failure-associated liver disease (IFALD) is a serious life-limiting complication that can occur throughout the clinical course of intestinal failure and its management by parenteral nutrition (PN). Despite this, there is a lack of a standardized definition for IFALD, which makes this insidious condition increasingly difficult to screen and diagnose in clinical practice. Attenuating the progression of liver disease before the onset of liver failure is key to improving morbidity and mortality in these patients. This requires timely detection and promptly addressing reversible factors. Although there are various noninvasive tools available to the clinician to detect early fibrosis or cirrhosis in various chronic liver disease states, these have not been validated in the patient population with IFALD. Such tools include biochemical composite scoring systems for fibrosis, transient elastography, and dynamic liver function tests. This review article aims to highlight the existing real need for an accurate, reproducible method to detect IFALD in its early stages. In addition, we also explore the role PN plays in the pathogenesis of this complex multifactorial condition. Various aspects of PN administration have been implicated in the etiology of IFALD, including the composition of the lipid component, nutrient excess and deficiency, and infusion timing. We aim to highlight the clinical relevance of these PN-associated factors in the development of IFALD and how these can be managed to mitigate the progression of IFALD.

The most common chronic liver illness worldwide is metabolic dysfunction linked to fatty liver disease (MAFLD), which is poorly understood by doctors and patients. Many people with this disease develop steatohepatitis, cirrhosis and its consequences, as well as extrahepatic manifestations; these conditions are particularly common if they are linked to diabetes mellitus or obesity. A breakthrough with numerous benefits is the switch from NAFLD to MAFLD in terms of terminology and methodology. The diagnosis of MAFLD is based on affirmative criteria; unlike NAFLD, it is no longer based on exclusion. The diagnosis of MAFLD and the evaluation of steatosis and fibrosis is achieved using liver biopsy and non-invasive laboratory or radiographic techniques. We briefly address the most recent developments in MAFLD epidemiology and diagnosis.

Recent studies have suggested an association between H. pylori and metabolic-disfunction associated fatty liver disease (MASLD). However, epidemiologic studies have yielded inconsistent results. We aim to evaluate the association of H. pylori and G-allele PNPLA3 in MASLD diagnosis, and markers of severity.

A multi-center cross-sectional study was conducted. A total 224 functional dyspepsia (FD) patients cohort who underwent gastroscopy was selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, LSM by VCTE, gastric biopsies, H. pylori status, and rs738409 PNPLA3 were evaluated. A second retrospective cohort of 86 patients with biopsy-proven MASLD who underwent gastroscopy with gastric biopsies was analyzed.

In the FD cohort MASLD was observed in 52%, and H. pylori-positive in 51%. H. pylori infection was associated with MASLD prevalence, but in multivariate analyses adjusted for G-allele PNPLA3, it became not significant. Then in MASLD-only dyspeptic cohort, H. pylori infection was significantly linked to elevated serum AST levels and increased liver stiffness measurements, suggesting a potential role in liver injury and fibrosis. Histopathological analysis in biopsy-proven MASLD patients further supported these findings, showing a significant association between H. pylori infection and increased NAS score, fibrosis stage, and prevalence of MASH. Notably, the combination of H. pylori infection and G-allele PNPLA3 appeared to exacerbate MASLD severity beyond individual effects.

Our results suggest that H. pylori infection may play a role in the progression of liver injury and fibrosis in patients with MASLD, especially in those with specific genetic predispositions.

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of Inoviridae was associated with both diabetes and liver steatosis. Diabetes was further associated with the enrichment of predominantly temperate Escherichia phages, some of which possessed virulence factors. Liver steatosis was associated with the depletion of Lactococcus phages r1t and BK5-T, and enrichment of the globally prevalent Crassvirales phages, including members of genus cluster IX (Burzaovirus coli, Burzaovirus faecalis) and VI (Kahnovirus oralis). The Lactococcus phages showed strong correlations and co-occurrence with Lactococcus lactis, while the Crassvirales phages, B. coli, B. faecalis, and UAG-readthrough crAss clade correlated and co-occurred with Prevotella copri. In conclusion, we identified the gut phageome signatures for two closely linked metabolic diseases with significant global burden. These phage signatures may have utility in risk modeling and disease prevention in this high-risk population, and identification of potential bacterial targets for phage therapy.IMPORTANCEPhages influence human health and disease by shaping the gut bacterial community. Using stool samples from a high-risk Mexican American population, we provide insights into the gut phageome changes associated with diabetes and liver steatosis, two closely linked metabolic diseases with significant global burden. Common to both diseases was an enrichment of Inoviridae, a group of phages that infect bacterial hosts chronically without lysis, allowing them to significantly influence bacterial growth, virulence, motility, biofilm formation, and horizontal gene transfer. Diabetes was additionally associated with the enrichment of Escherichia coli-infecting phages, some of which contained virulence factors. Liver steatosis was additionally associated with the depletion of Lactococcus lactis-infecting phages, and enrichment of Crassvirales phages, a group of virulent phages with high global prevalence and persistence across generations. These phageome signatures may have utility in risk modeling, as well as identify potential bacterial targets for phage therapy.