Recent clinical consensus statements have emphasized a shift from diagnosing obesity with body mass index (BMI) requiring confirmation with surrogate markers such as waist circumference-to-height ratio (WHtR). WHtR is a highly sensitive and specific predictor of dual-energy X-ray absorptiometry-measured total body fat mass and abdominal fat mass but not lean mass. However, newly developed WHtR adiposity cut points warrant external validation before clinical application.

To examine whether new WHtR cut points predict liver steatosis and fibrosis in a multiracial population.

Data from 6464 (54% female) multiracial US participants from the National Health and Nutrition Examination Survey conducted between 2021 and 2023 were analyzed. Liver fibrosis was assessed with transient elastography and staged as fibrosis stage F0 to F4 and liver steatosis graded S0 to S3.

Participants' mean (SD) age was 47.3 (20.9) years. The prevalence of WHtR cut points of 0.40 to <0.50 (normal fat mass), 0.5 to <0.53 (high fat mass), and ≥0.53 (excess fat mass) was 20.3%, 13.6%, and 64.5%. Multivariable-adjusted WHtR high fat mass predicted liver steatosis (odds ratio 1.63 [95% confidence interval 1.16-2.29] P = .005) and fibrosis (1.31 [1.01-1.70] P = .043). Excess WHtR fat mass was associated with liver steatosis (4.02 [2.87-5.64] P < .001) and fibrosis (1.61 [1.03-2.54] P = .038). Normal WHtR fat mass predicted lower odds of liver steatosis (0.52 [0.37-0.73] P < .001) and fibrosis/cirrhosis (0.48 [0.30-0.76] P < .001). WHtR high fat mass and excess fat mass separately predicted higher odds of liver steatosis 1.6-fold and 6-fold, respectively, better than BMI-overweight and BMI-obesity.

The simple and universally accessible WHtR cut points may be useful in clinical and public health practice for obesity screening, diagnosis, and management.

Currently, there is an absence of a standardised protocol for the preoperative detection of hepatic steatosis (HS) in living liver donors. A steatotic liver graft jeopardises the outcome of the recipient with multiple potential complications. Vibration-controlled transient elastography (Fibroscan®) provides a controlled attenuation parameter (CAP), which we have utilised in our assessment of HS in living liver donors. This approach offers a promising avenue for the advancement of preoperative evaluation protocols.

In the period spanning from October 2022 to July 2024, a cohort of 67 liver donors were subjected to preoperative vibration-controlled transient elastography (Fibroscan®) and either preoperative or intraoperative liver biopsy. HS was defined as a fat content exceeding 10%. CAP readings were juxtaposed with liver biopsy results for the diagnosis of HS. Donors were categorised into three categories with HS <5%, 5-10% and those with HS >10% were rejected as per our institutional protocol. This facilitated a comprehensive evaluation of HS in the context of living donor liver transplantation.

CAP was very accurate in detecting HS, with an area under the receiver operating characteristic curve of 0.99 (P < 0.05). Statistical analysis determined that a CAP cutoff value of 266 dB/m provides a sensitivity of 100% and a specificity of 98.4% for predicting HS >10%. Corresponding positive predictive value (PPV) is 85.71%, while the negative predictive value is 100%. Univariate analysis determined body mass index (BMI), age and serum triglyceride levels were associated with CAP; however, multivariate linear regression revealed an association with only BMI (P < 0.001) and age (P < 0.002). When a lower fat threshold of 5% was considered to define HS with the same cut off of CAP, the sensitivity reduced to 66.7% and specificity was 98.3% The recipients of donors with HS of 5%-10% did not show any negative outcomes.

CAP demonstrates significant potential as a predictive tool for hepatic steatosis (HS) in living liver donors. Notably, BMI and age have been identified as independent factors associated with CAP values.

The weight-adjusted waist index (WWI) is emerging as a novel indicator for assessing obesity, which is known to correlate with nonalcoholic fatty liver disease (NAFLD), a condition that can lead to hepatic steatosis and fibrosis. This research aims to explore the possible link between WWI and liver steatosis and fibrosis. We conducted a cross-sectional analysis using data from 2017 to 2020 National Health and Nutrition Examination Survey. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to diagnose hepatic steatosis and fibrosis, respectively, by vibration-controlled transient elastography, and multivariate logistic regression analysis was employed to examine the association between WWI and the 2. The non-linear relationship was described using threshold effect analyses and fitting smoothed curves. We also performed interaction tests and subgroup analyses, considering factors such as age, gender, body mass index, hypertension, diabetes, and smoking habits. Receiver operating characteristic curves were used to estimate cutoff points for identifying NAFLD. This study included 5535 adults. Results showed that higher levels of WWI are correlated with higher CAP scores, and the strong association between WWI and CAP was still evident after accounting for all covariates (odds ratios = 12.22, 95% confidence interval: 8.63-15.80). Subgroup analyses found a robust positive correlation between WWI and CAP in individuals with hypertension (P for interaction = .018). A non-linear positive correlation with a breakpoint of 11.12 was identified between WWI and CAP. But no significant correlation between WWI and LSM was found through multiple regression analyses (odds ratios = 0.10, 95% confidence interval: -0.17 to 0.37). Nevertheless, based on smoothed curve fitting, WWI and LSM formed a U-shaped relationship, showing a positive connection when WWI was above 11, when WWI dropped below 11, it showed a negative connection. Finally, the receiver operating characteristic analysis results indicated that the WWI cutoff point for identifying NAFLD was 10.8870. To validate these results, further extensive and prospective studies are required.

Attenuation Imaging (ATI) and controlled attenuation parameter (CAP) are non-invasive ultrasound-based methods for diagnosing hepatic steatosis. However, reports on the clinical usefulness of ATI are limited. We aimed to compare the ability of ATI and CAP to diagnose hepatic steatosis with magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) as the reference standard.

We performed a prospective multicenter study of 562 patients with chronic liver disease who underwent ATI, CAP, and MRI-PDFF. Patients with skin-to-liver capsule distance (SCD) ≤ 25 mm underwent CAP with an M probe; those with SCD > 25 mm underwent CAP with an XL probe. MRI-PDFF was used as the reference standard: S0 corresponds to MRI-PDFF < 5.2%, S1 to 5.2% ≤ MRI-PDFF < 11.3%, S2 to 11.3% ≤ MRI-PDFF < 17.1%, and S3 to MRI-PDFF ≥ 17.1%.

The correlation coefficients for ATI and MRI-PDFF stratified by body mass index (< 30, ≥ 30 kg/m2), SCD (< 25, ≥ 25 mm), 2-dimensional share wave elastography (< 1.8 m/s), fibrosis-4 index (≤ 2.67), albumin-bilirubin score (< - 2.60) and type IV collagen 7 s (< 5.0 ng/ml) were significantly higher than those for CAP and MRI-PDFF. Areas under the receiver operating characteristics (95% CI) for ATI and CAP were 0.895 (0.869-0.922) and 0.845 (0.809-0.881) for ≥ S1 steatosis, 0.944 (0.926-0.963) and 0.881(0.852-0.910) for ≥ S2 steatosis, and 0.928 (95% CI 0.906-0.950) and 0.860 (95% CI 0.829-0.890) for S3 steatosis. ATI had higher diagnostic performance for all hepatic steatosis grades than CAP.

ATI is a more useful non-invasive method for diagnosing hepatic steatosis than CAP.

A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis.

This was a real-world prospective study including a large dataset of MASLD patients with paired VCTE and liver biopsy from 6 centers. A total of 1196 patients were recruited and divided in training (3 centers, Spain), internal validation (2 centers, Spain), and external validation (1 center, United States) cohorts. In patients with indeterminate liver stiffness measurement (LSM) (8-12 kPa), a diagnostic algorithm was developed to identify significant fibrosis, defined as histological stage ≥F2. Statistical analysis was performed using Gaussian mixture model (GMM) and k-means unsupervised clusterization.

From the eligible population, 33%, 29%, and 31% had indeterminate VCTE in the training, internal and external validation samples, respectively. The controlled attenuation parameter allowed the differentiation of GMM clusters with a cutoff of 280 dB/m (area under the curve, 0.89; 95% confidence interval, 0.86-0.97). Within patients with <280 dB/m, a LSM between 8.0-9.0 kPa showed a 93% sensitivity and a 91% negative predictive value to exclude significant fibrosis. Among patients with ≥280 dB/m, a LSM between 10.3 and 12.0 kPa diagnosed significant fibrosis with a 91% specificity. Applying this algorithm to the validation cohorts, 36% of the indeterminate VCTE were reallocated. The reallocated high-risk group showed a prevalence of 86% significant fibrosis, opening the therapeutic window for MASLD patients.

To identify candidates for MASLD treatment among indeterminate VCTE, an algorithm-based on the sequential combination of LSM and controlled attenuation parameter thresholds can optimize the diagnosis of moderate-to-advanced fibrosis.

Gastrointestinal (GI) symptoms are common in patients with Williams-Beuren syndrome (WBS), but their prevalence and possible causes are not yet fully known. This study assessed GI symptoms' prevalence and their possible origin by performing a predefined set of tests in adult WBS patients. Laboratory tests and a questionnaire were administered to assess GI symptoms and dietary habits. All the patients underwent the urea breath test, H2-lactose and H2-glucose breath tests, and intestinal ultrasound (IUS) and vibration-controlled transient elastography for liver stiffness measurement (LSM) and controlled attenuation parameter (CAP, dB/m). Thirty-one patients were enrolled (72% of the whole cohort, 17 males, median age 32 years). Gastroesophageal reflux disease (GERD) symptoms were reported in 29% of the patients, abdominal pain in 26%, and altered bowel habits in 48%. Pathologic signs at (IUS) were present in 60% of the cases. Prevalence was 0.26 (95% CI 0.12-0.44) for Helicobacter pylori infection and 0.61 (95% CI 0.42-0.78) for lactose intolerance. LSM was > 6 kPa (in the range of a fibrosis score > F1) in three patients, and CAP values were > 268 dB/m (corresponding to a steatosis score > S2, e.g., moderate steatosis) in nine. The presence of altered bowel habits was significantly related to chronic abdominal pain (OR 13.1, p = 0.03). Increased BMI (> 28 kg/m2) (OR 10.8, p = 0.04) was associated with the presence of moderate-severe hepatic steatosis. After specific treatment and dietary counseling, most patients reported resolution/improvement of symptoms, whereas a few retained/developed symptoms during follow-up. Chronic abdominal pain, GERD symptoms, and unbalanced metabolic parameters were common in our WBS patients, together with an increased prevalence of lactose intolerance/colonic diverticula. Specific counseling and treatment improved symptoms for most patients.

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

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

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

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

We assessed the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and significant liver fibrosis in adults with type 1 diabetes mellitus (T1DM) and the association of MASLD with insulin sensitivity and continuous glucose monitoring metrics.

We consecutively enrolled 198 adults with T1DM undergoing vibration-controlled transient elastography with liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). All participants had a continuous glucose monitoring (CGM) device. Insulin sensitivity was evaluated by estimated glucose disposal rate (eGDR). MASLD was defined as CAP ≥ 248 db/m and the presence of at least one cardiometabolic risk factor. Significant liver fibrosis was defined as LSM ≥ 7 kPa.

Patients had a mean age of 56 years, mean BMI of 26.0 ± 5.9 kg/m2, and mean eGDR of 7.1 ± 2.3 mg/kg/min. 73 (37%) patients had MASLD (using a CAP threshold of 274 dB/m), 16 (8.1%) of whom had significant liver fibrosis. MASLD was associated with a significantly lower eGDR (beta coefficient = -0.367, 95% confidence interval -0.472 to -0.261; p < 0.001). This association remained significant, even after adjustment for age, sex, body mass index, plasma triglycerides, diabetes duration, daily insulin dose, time above the range of glucose levels, LSM and chronic kidney disease. No association was observed between MASLD and CGM-derived metrics. These results were not different when we used a CAP threshold of 274 dB/m for diagnosing MASLD.

In T1DM, MASLD was inversely associated with eGDR and biomarkers of insulin resistance but not with CGM-derived metrics.

Steatotic liver diseases (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD). Our aim was to determine the age-standardized prevalence of fibrosis stages and cirrhosis in US adults with different subtypes of SLD.

We utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017 to 2023. SLD was defined by a controlled attenuation parameter (CAP) ≥280 dB/m. MASLD, MetALD, and ALD were defined according to the new nomenclature. Fibrosis and cirrhosis were estimated by liver stiffness measurements.

The age-standardized prevalence of SLD was 37.08% (MASLD: 32.42%, MetALD: 2.20%, and ALD: 1.29%) with males having higher prevalence rates versus females [SLD (42.40% vs. 31.59%), MASLD (35.84% vs. 28.88%), MetALD (2.82% vs. 1.56%), and ALD (2.17% vs. 0.38%) (all P < 0.03)]. For MASLD, the highest burden was observed in Mexicans (43.96%), followed by Whites (31.75%), Hispanics (32.69%), Asians (32.41%), and Blacks (27.39%). MetALD was most prevalent among Whites (2.56%) and least prevalent among Asians (0.25%). Between 2017 and 2020 and 2021 and 2023, the prevalence of SLD and its subtypes with fibrosis and cirrhosis increased, coinciding with rising alcohol consumption. Among individuals with MASLD, component of metabolic syndrome (type 2 diabetes and Obesity, especially severe obesity with BMI ≥40 kg/m²) were associated with increased risk of fibrosis and cirrhosis.

The burden of SLD, its subtypes, and associated fibrosis in the US is substantial. This highlights an urgent need for targeted public health strategies to manage the rising burden of this important liver disease in the US population.

Relative fat mass (RFM) is a novel, easily calculated, and cost-effective index of fat content and distribution in the body, associated with the odds of developing various obesity-related diseases. However, its association with metabolic dysfunction associated steatotic liver disease (MASLD) and severe hepatic steatosis (SHS) is underexplored. This study aims to examine the relationship between RFM and the odds of having MASLD or SHS in the general adult population.

This was a population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (2017.01-2020.03). The aim of the statistical analysis was to examine the association between RFM and the prevalence of MASLD and SHS. Logistic regression was applied to explore this relationship. Nonlinear associations between RFM levels and MASLD or SHS prevalence were assessed using smoothed curve fitting and threshold effect models. Subgroup analyses were conducted to evaluate the consistency of this association across different population groups.

A total of 6699 participants were included in this study, of whom 2825 had MASLD and 1834 had SHS. After adjusting for confounders, significant positive associations were observed between RFM and the prevalence of MASLD and SHS (odds ratio [OR]: 1.22, 95% confidence interval [CI: ] 1.18-1.26 and OR: 1.26, 95% CI: 1.21-1.30). Smoothed curve fitting and threshold effect analysis showed a nonlinear relationship between RFM and the prevalence of MASLD and SHS, with thresholds of 41.96 for MASLD prevalence and 40.42 for SHS prevalence. When the subgroups were analyzed according to sex, age, race, education level, smoking status, household income, body mass index, hypertension, and diabetes, no significant interactions were found between RFM and most subgroups.

Our results demonstrated a positive nonlinear relationship between RFM and the prevalence of MASLD and SHS, with a threshold effect. Lower RFM levels are associated with lower odds of MASLD and SHS. These findings suggest that RFM may serve as a simple, cost-effective tool for identifying individuals at increased odds of NAFLD and SHS in the general population.

Fatty liver disease (FLD), characterized by hepatic lipid accumulation, impairs quality of life and can progress to cirrhosis and hepatocellular carcinoma, imposing a healthcare burden. This study investigates the association between the aggregate index of systemic inflammation (AISI) and FLD prevalence, evaluating AISI's potential as an early biomarker for risk assessment.

Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database, which encompasses the years 2017 through 2020. Participants were chosen based on the availability of controlled attenuation parameter (CAP) scores derived from transient elastography (TE), a technique utilized for assessing liver steatosis. The formula employed to compute the AISI is as follows: AISI = N × P × M / L, where N, P, M, and L refer to neutrophils, platelets, monocytes, and lymphocytes, respectively. Additionally, demographic, socioeconomic, dietary, and health-related information was gathered. Logistic regression models were utilized to pinpoint risk factors associated with FLD, and a nomogram was created to forecast FLD risk.

Of the 3,961 participants, 2,377 (60.0%) were diagnosed with FLD based on a CAP score ≥ 248 dB/m. Elevated AISI was significantly associated with FLD (P = 0.021). Other significant risk factors included sex, age, BMI, race, marital status, hypertension, and diabetes. The nomogram demonstrated excellent discriminatory performance with an AUC of 0.814 (95% CI: 0.800, 0.827) and good calibration.

This study reveals a significant, independent association between elevated AISI and increased FLD risk in the U.S. population, even after adjusting for confounders. AISI demonstrated good discriminative performance for FLD, but its effect size suggests it should supplement, not replace, existing clinical risk assessment tools. AISI, a cost-effective biomarker, holds potential for enhancing FLD screening, particularly in resource-limited settings.

The link between cardiometabolic markers and hepatic steatosis and liver fibrosis in non-hypertensive, non-diabetic populations remains unclear. A study was conducted using data from the National Health and Nutrition Examination Survey. Hepatic steatosis and liver fibrosis were assessed using vibration-controlled transient elastography. Logistic regression and restricted cubic splines (RCS) were used to evaluate the associations of cardiometabolic index (CMI), atherogenic index of plasma (AIP), triglyceride-glucose index (TyG), and estimated glucose disposal rate (eGDR) on hepatic steatosis and estimated fibrosis. Mediation analysis examined the role of insulin resistance (HOMA-IR) and liver enzymes. Among 1489 participants, 39.15% had hepatic steatosis and 2.82% had liver fibrosis. Higher CMI (OR = 3.967, 95%CI: 2.297, 6.851), AIP (OR = 3.255, 95%CI: 2.031, 5.216), TyG (OR = 3.689, 95%CI: 2.363, 5.760), and FLI (OR = 2.695, 95%CI: 1.997, 7.816) tertiles of Q3 were linked to increased hepatic steatosis odds, while eGDR reduced odds (OR = 0.217, 95%CI: 0.127, 0.373). The AUC values of these four cardiac markers were greater than FLI, among which eGDR showed the highest predictive value (AUC = 0.781). In the hepatic steatosis population, CMI (OR = 1.419, 95%CI: 1.033, 2.747), AIP (OR = 5.527, 95%CI: 1.082, 28.242), and TyG (OR = 2.345, 95%CI: 1.180, 4.661) were also showed significant association with liver fibrosis, while eGDR and FIB-4 were not associated with liver fibrosis. AIP had the highest discriminative ability for liver fibrosis (AUC = 0.798). Mediation analysis showed HOMA-IR mediated 25.50%~36.20% of cardiometabolic markers' associations with hepatic steatosis, followed by liver enzymes. Cardiometabolic markers are strongly linked to hepatic steatosis and liver fibrosis in populations without traditional risk factors, even outperforming the established hepatic steatosis and the fibrosis marker, highlighting their potential for early liver disease risk identification in seemingly healthy individuals.

Steatotic liver disease (SLD) prevalence in adults is estimated at 30%, but older populations are understudied. Here, SLD prevalence and associated risk factors were assessed 1,021 Whitehall II study participants (mean age 72.5) using transient elastography (FibroScan). SLD was present in 33.3% (CAP ≥ 275 dB/m), with most classified as metabolic dysfunction-associated SLD. Only 2.4% had significant fibrosis ( ≥ 7.9 kPa). Adjusted for age and sex, SLD was associated with low physical activity (OR 1.60, 95% CI 1.13-2.27), poorer motor function (SF-36 PCS OR 1.21, 95% CI 1.05-1.40), difficulties in activities of daily living (OR 3.19, 95% CI 1.17-8.64), and multimorbidity (OR 1.45, 95% CI 1.22-1.73). These associations persisted after adjustment for socioeconomic, behavioural, and cardiometabolic risk factors. Frailty was associated with SLD at higher CAP thresholds ( ≥ 290 dB/m). In this older adult sample, SLD is common and appears more as a marker of multimorbidity and low physical activity than significant fibrosis.

The mechanistic role of gut microbiota in metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD) is increasingly recognized. Despite their close association, comparative data regarding gut dysbiosis in these disorders are limited. This study included 22 healthy controls and 180 patients (90 MASLD, 60 CKD, and 30 both diseases with sex- and age-matched). Fecal bacterial 16 S ribosomal RNA sequencing and butyryl-CoA: acetate CoA transferase (BCoAT) gene expression were analyzed. Plasma intestinal fatty acid binding protein (I-FABP), representing intestinal barrier dysfunction, was assessed using the ELISA method. Our data showed that alpha and beta diversities of gut microbiota differed between MASLD and healthy controls. However, only beta diversities were different between CKD and healthy individuals. The MASLD and CKD groups displayed fewer SCFA-producing genera, particularly Bifidobacterium, than healthy controls. Fecal BCoAT levels were inversely correlated with eGFR and I-FABP levels. Patients with CKD had significantly enriched pathogenic bacteria, reduced BCoAT, and increased I-FABP levels versus MASLD. Combining significant bacterial genera discriminated MASLD from CKD with high diagnostic accuracy (AUC of 0.90). Among patients with both diseases, gut microbial alterations showed mixed characteristics of MASLD and CKD. These data highlighted the shared and distinct gut dysbiosis and related biomarkers, which could provide a better understanding of MASLD and CKD pathogenesis.

In 2023, nonalcoholic fatty liver disease was renamed metabolic dysfunction-associated steatotic liver disease by the American and European liver associations. This new nomenclature recognizes metabolic dysfunction as the central driver of the disease, and the diagnostic criteria now require the presence of hepatic steatosis plus at least one of five cardiometabolic risk factors. B-mode ultrasonography remains the most common and practical method for detecting hepatic steatosis, although newer ultrasound techniques based on attenuation, backscatter, and speed of sound have gained traction as tools to diagnose and quantify hepatic steatosis. Additionally, ultrasound elastography is increasingly used in routine clinical practice to assess liver fibrosis, diagnose cirrhosis, and identify clinically significant portal hypertension.

Nomenclature for steatotic liver disease has been updated to include metabolic dysfunction-associated steatotic liver disease (MASLD), which requires the presence of hepatic steatosis and at least one cardiometabolic risk factor. The prevalence of MASLD in adolescents is understudied.

To determine the prevalence of suspected MASLD among adolescents in the United States and to examine the relationships between elevated alanine aminotransferase (ALT) and cardiometabolic risk factors.

A cross-sectional analysis of the National Health and Nutrition Examination Survey from 2011 to 2020 was conducted for adolescents aged 12-19 years. Elevated ALT was defined using sex-specific biological upper limits: > 26 U/L for males and > 22 U/L for females. Suspected MASLD was identified by elevated ALT and at least one cardiometabolic risk factor. Adolescents with elevated ALT were categorised as having suspected MASLD, elevated ALT due to other causes or cryptogenic ALT elevation.

Overall, 14.6% of adolescents had elevated ALT. Of these, 77.2% had suspected MASLD, 20.2% had cryptogenic ALT elevation, 1.9% took hepatotoxic medications and 0.7% had viral hepatitis. Body mass index had the strongest association with elevated ALT (OR 3.55), followed by high triglycerides (OR 2.09), low HDL cholesterol (OR 2.05) and high blood pressure (OR 1.93).

Most adolescents with elevated ALT met MASLD criteria, yet a portion lacked cardiometabolic risk factors or other identifiable causes. These results support the adoption of MASLD criteria in adolescents while indicating a need for further research into cryptogenic ALT elevation in paediatric populations.

The stress hyperglycemia ratio (SHR) offers a more nuanced understanding of glucose metabolism by factoring in the background glycemia through the component of Hemoglobin A1c. The association of SHR with cardiovascular and cerebrovascular diseases has been established, but the relationship between SHR and the risk of nonalcoholic fatty liver disease (NAFLD) remains unexplored. This study aimed to elucidate the relationship between the two among U.S. adults with diabetes or prediabetes.

A total of 1409 participants diagnosed with diabetes or prediabetes from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were included in this study. Multiple logistic regression models (ranging from unadjusted to fully adjusted), restricted cubic splines, and subgroup analyses were employed to determine the relationship between SHR and NAFLD risk and to assess the stability of this relationship across different populations. The average age of all participants was 54.65 years, with males accounting for 47.91 %, and the prevalence of NAFLD being 68.77 %. A fully adjusted logistic regression model indicated a positive association between SHR levels and the risk of NAFLD. Specifically, for each one standard deviation increase in SHR, the risk of NAFLD increased by 20 % (OR, 1.2; 95 % CI, 1.0-1.4). Both the trend test and the restricted cubic splines suggested a linear relationship between the two variables (p for trend <0.05, p for nonlinear = 0.390). Subgroup analysis demonstrated that this positive association remained consistent across most subgroups.

SHR was identified as a valuable index for predicting the risk of NAFLD among U.S. adults with diabetes or prediabetes.

Data regarding the risk of incident type 2 diabetes (T2D) and prediabetes among patients with hepatitis C virus (HCV) achieving direct-acting antivirals (DAAs)-induced sustained virologic response (SVR12) remains limited.

A total of 1079 patients, including 589 with normoglycemia and 490 with prediabetes, who underwent biannual fasting glucose and glycosylated haemoglobin (HbA1c) assessment for a median post-SVR12 follow-up of 5.5 years, were enrolled. We reported the crude (cIRs) and age-standardised incidence rates (ASIRs) of T2D and prediabetes. Factors associated with incident T2D and prediabetes were assessed using the Cox proportional hazards models.

The cIRs of T2D and prediabetes were 1.18 and 8.99 per 100 person-years of follow-up (PYFU), respectively. Additionally, the ASIRs of T2D and prediabetes were 1.09 (95% CI: 0.76-1.53) and 8.47 (95% CI: 7.23-9.90) per 100 PYFU. Prediabetes (adjusted hazard ratio [aHR]: 4.71; 95% confidence interval (CI): 2.55-8.70, p < 0.001), body mass index (BMI) per kg/m2 increase (aHR: 1.17; 95% CI: 1.09-1.26, p < 0.001) and liver stiffness measurement (LSM) per kPa increase (aHR: 1.05; 95% CI: 1.02-1.09, p = 0.001) were associated with a higher risk of incident T2D. Age per year increase (aHR: 1.02; 95% CI: 1.01-1.03, p < 0.001) was associated with a higher risk of incident prediabetes.

The incidence rates of T2D and prediabetes remain substantial among patients after HCV eradication. Lifestyle modification, drug therapy and regular monitoring of glycemic status are crucial for patients at risk of developing T2D and prediabetes following HCV clearance.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most prevalent chronic liver condition in adolescents. The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has shown promise in adult MAFLD detection but requires pediatric-specific validation, particularly when combined with anthropometric measures. This study investigated the association between modified TyG indices and MAFLD, and evaluated their predictive value in adolescents.

This cross-sectional study analyzed data from 532 adolescents (12-18 years) in the 2017-2020 National Health and Nutrition Examination Survey (NHANES) with complete records. MAFLD diagnosis was based on transient elastography plus metabolic criteria. The investigators employed multivariate linear regression and restricted cubic splines (RCS) to examine linear and nonlinear relationships between modified TyG indices and CAP values. Subgroup analyses were stratified by obesity status, and sensitivity analyses were performed on the NAFLD cohort (n = 527). Receiver operating characteristic (ROC) curve analysis, using Youden's index, evaluated the predictive performance of TyG indices for MAFLD identification.

Among 130 MAFLD adolescents (vs 402 controls), modified TyG indices demonstrated significantly stronger associations with CAP in fully adjusted models compared to the original TyG index. TyG-WC showed the highest diagnostic accuracy (AUC = 0.923, 95%CI:0.900-0.947), followed by TyG-BMI (AUC = 0.917) and TyG-WHtR (AUC = 0.915), while the original TyG index performed poorly (AUC = 0.673). Subgroup analyses revealed particularly strong associations in non-obese participants, and sensitivity analyses confirmed result robustness after excluding potential confounders. Optimal cutoff values provided clinically useful screening thresholds, with TyG-WC achieving 94% sensitivity at 665.94.

This study demonstrates that modified TyG indices incorporating anthropometric parameters (particularly TyG-WC) significantly outperform the original TyG index for MAFLD detection in adolescents, with superior diagnostic accuracy (AUC 0.915-0.923). The robust predictive performance maintained in sensitivity analyses and non-obese subgroups supports their clinical utility as simple, non-invasive screening tools for pediatric MAFLD risk stratification.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is widespread worldwide, and a strong link between MASLD and cardiometabolic risk factors (CMRFs) was highlighted in this study.

This study characterized the prevalence of MASLD in adolescent population and overlapping CMRFs conditions in MASLD.

This is a cross-sectional study of US adolescents aged 12 to 19 years in the 2017 through 2020 cycles of the National Health and Nutrition Examination Survey. The relationship between CMRFs and liver steatosis, evaluated by the median controlled attenuation parameter (CAP), was assessed.

The prevalence of MASLD in adolescents was 23.77%. Isolated overweight/obesity (35%) was the top CMRF. Non-Hispanic Black patients had the highest proportion of overweight/obesity plus elevated glucose (24%), whereas non-Hispanic Asians had the highest burden of dyslipidemia (2%, 14%, and 19%). Except for hypertension, overweight/obesity (β = 48.7; 95% CI, 43.4-54.0), hypertriglyceridemia (β = 15.5; 95% CI, 7.2-28.3), low HDL-C (β = 10.0; 95% CI, 3.1-16.9), elevated glucose (β = 6.9; 95% CI, 0.6-13.2) were all significantly associated with increased CAP values. Increased CAP was linked to the synergistic interactions between overweight/obesity and dyslipidemia or elevated glucose (overweight/obesity and elevated glucose: relative excess risk due to interaction [RERI] = 8.21, attributable proportion due to interaction [AP] = 0.45, synergy index [SI] = 1.91; overweight/obesity and hypertriglyceridemia: RERI = 19.00, AP = 0.69, SI = 3.53; overweight/obesity and low high-density lipoprotein cholesterol: RERI = 10.83, AP = 0.58, SI = 2.61). Adolescents with combination of overweight/obesity, dyslipidemia (β = 15.1; 95% CI, 0.1-30.2) and combination of overweight/obesity, dyslipidemia and elevated glucose (β = 48.0; 95% CI, 23.3-72.6) had a significantly higher CAP values.

The prevalence of MASLD was alarmingly high in adolescents, and overweight/obesity was the most important CMRF. Overweight/obesity and dyslipidemia or elevated glucose had positive additive interaction effects on liver steatosis.

Cardiometabolic index (CMI) was proposed ten years ago as an indicator combining obesity and dyslipidemia. This study aimed to investigate the relationships between newly modified CMI (MCMI) with non-alcoholic fatty liver disease (NAFLD) and liver fibrosis.

This cross-sectional study included participants in the 2017-2018 National Health and Nutrition Examination Survey database (NHANES). Linear regression was used to explore the relationship between MCMI and Baseline characteristics. Logistic regression was conducted to analyze the correlation among MCMI with NAFLD and liver fibrosis. Furthermore, restricted cubic spline (RCS) was performed to estimate nonlinear relationships. Receiver operating characteristic curve (ROC) was used to assess the diagnostic performance of MCMI for NAFLD and liver fibrosis.

A total of 1385 participants were enrolled in the study. After adjusting covariates, participants with high MCMI were related to increased risk of NAFLD (OR = 3.52, 95%CI: 1.44-8.61), compared with those having low MCMI. A linear association was observed between MCMI and NAFLD (p for nonlinear = 0.074), and a J-shaped nonlinear relationship was found between MCMI and liver fibrosis (p for nonlinear = 0.002). The area under the curve (AUC) for MCMI to identify NAFLD was 0.821 (95% CI 0.799-0.843), which was higher than that of CMI (AUC = 0.761, 95%CI: 0.735-0.786), fatty liver index for the U.S. population (USFLI, AUC = 0.799, 95%CI: 0.776-0.822), Triglyceride glucose index (TyG, AUC = 0.738, 95%CI: 0.712-0.765), NAFLD liver fat score (NLFS, AUC = 0.786, 95%CI: 0.761-0.810) and hepatic steatosis index (HSI, AUC = 0.799, 95%CI: 0.775-0.822).

The novel MCMI was positively corelated to the risk of NAFLD. In addition, MCMI was an effective predictor for both NAFLD and liver fibrosis.

The high-sensitivity C-reactive protein to albumin (CAR) ratio is a comprehensive measure of inflammation in vivo. Hepatic steatosis and fibrosis are significantly correlated with inflammation. The present study aimed to explore the possible associations between CAR and hepatic steatosis and fibrosis in the American population.

The study population involved the National Health and Nutrition Examination Survey (NHANES) participants from 2017 to 2020. The natural logarithm of CAR, calculated as Ln(CAR) with base "e," was used for further analyses. The relationships between Ln(CAR) and the controlled attenuation parameter (CAP) and between Ln(CAR) and liver stiffness measurement (LSM) were investigated through multivariate linear regression analysis. Interaction and subgroup analysis identified factors affecting these variables. Nonlinear relationships were elucidated by smoothing curves and threshold effect analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the CAR for non-alcoholic fatty liver disease (NAFLD). The results were adjusted for U.S. population estimates.

The study included a total of 7,404 individuals. Ln(CAR) was positively correlated with CAP in the fully adjusted model, with an effect value of β = 1.827 (95% CI, 0.611, 3.042). A more pronounced positive association was observed among participants with a BMI ≥ 25 kg/m2 in the subgroup analysis. An inverted U-shaped association was shown between Ln(CAR) and CAP through smooth curve fitting and a two-segment linear regression model, with an inflection point of (-9.594). ROC curve analysis showed that CAR had a moderate predictive value for NAFLD (AUC = 0.6895), with a sensitivity of 0.7276 and a specificity of 0.6092. No significant association was detected between Ln(CAR) and the LSM.

We demonstrate an inverted U-shaped relationship between Ln(CAR) and CAP risk within the U.S. demographic. Our results suggest that CAR may serve as a valuable diagnostic tool for NAFLD. Further prospective research is necessary to validate this conclusion.

To investigate the diagnostic performance of ultrasound attenuation imaging technology (USAT) in the evaluation of hepatic steatosis using magnetic resonance imaging proton density fat fraction (MRI PDFF) and histology as reference standards.

In this single-center, prospective study, the liver fat content of 117 potential liver donor candidates was assessed by USAT and MRI PDFF between April and August 2024. Intraoperative liver biopsy was performed in 47 liver donors. Cut-off values of 6%, 17%, 22%, and 5%, 33%, 66% were used for mild, moderate, and severe steatosis in MRI PDFF and histology, respectively. The correlation between USAT and MRI PDFF was evaluated using Spearman's rho technique. Receiver operating characteristic (ROC) analysis was performed for the diagnostic performance of USAT, and optimal USAT cut-off values for different grades of hepatosteatosis were obtained.

There was a very strong correlation between USAT and MRI PDFF (rho = 0.933, p < 0.001). For MRI PDFF values greater than 6%, the area under the curve (AUC) was 0.97 [95% confidence interval (CI): 0.93-0.99] (p < 0.001). USAT cut-off values for differentiating between different grades of liver steatosis were 0.57, 0.68, and 0.76 dB/cm/MHz for mild, moderate, and severe steatosis, with sensitivities of 88.9%, 90.0%, and 86.7%, respectively. For histologically confirmed steatosis greater than 5%, the AUC was 0.94 (95% CI: 0.83-0.99) (p < 0.001), with a cut-off of 0.56 dB/cm/MHz for 84.6% sensitivity.

USAT demonstrates excellent diagnostic accuracy in both the quantification and grading of hepatic steatosis.

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of metabolic dysfunction-associated steatotic liver disease, advanced liver fibrosis, and metabolic dysfunction-associated steatohepatitis (MASH). We evaluated the prevalence and severity of metabolic dysfunction-associated steatotic liver disease among patients with T2DM at their first referral to diabetes clinics and assessed the effectiveness of the 2-tier screening approach by Fibrosis-4 (FIB-4) and vibration-controlled transient elastography (VCTE).

Consecutive patients with T2DM from 6 different diabetes clinics were prospectively enrolled. Liver stiffness measurement (LSM) was assessed by VCTE, whereas liver steatosis by controlled attenuation parameter (Fibroscan, Echosens, France). "At-risk MASH" was assessed by FibroScan-aspartate aminotransferase score.

Eight hundred patients (median age: 59, 53-65 years; males: 485, 60.6%) met the inclusion criteria. Prevalence of liver steatosis (controlled attenuation parameter ≥ 248 db/m) was 73.6%. The proportion of patients at medium/high risk of advanced liver fibrosis (LSM ≥ 8.0 kPa) was 16.9%. Patients with "at-risk MASH" (FibroScan-aspartate aminotransferase > 0.67) were 12.0%. A 2-tier screening for advanced liver fibrosis by FIB-4 and VCTE would have led to 70 patients (8.8%) referred to liver clinics with a false-negative rate of 9.6% (n = 77; patients with FIB-4 < 1.3 and LSM ≥ 8.0 kPa). At multivariate analysis, overweight/obesity (odds ratio = 3.13, 95% confidence interval 1.23-7.97) and elevated alanine aminotransferase (odds ratio = 1.91, 95% confidence interval 1.17-3.10) were independently associated with LSM ≥ 8.0 kPa in patients with FIB-4 < 1.3.

In diabetes clinics, the 2-tier screening using FIB-4 and VCTE is effective for the identification of patients with T2DM to be referred to hepatologists. VCTE referral may be considered for patients with overweight/obesity and elevated alanine aminotransferase classified as at low risk of advanced liver fibrosis by FIB-4.

Background/Objectives: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Through analysis of the trends and disparities regarding cardiovascular disease (CVD) among individuals with MASLD, identifying the leading cause of death in this population is crucial. Methods: We conducted a cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 2017-2020 data. MASLD was identified by using clinical profiles and liver ultrasonography to exclude other liver diseases. We estimated the prevalence of CVD among individuals with MASLD and calculated the prevalence ratios for those with and without MASLD. Results: In 2017-2020, MASLD affected 31.2% or 61.9 million US adults, and 17.0% (95% confidence interval: 13.7-20.3%) of these individuals had CVD. The absolute CVD prevalence in individuals with MASLD doubled from that in the NHANES III cohort, which was 8.7% (6.4%, 10.9%). These increases were especially notable among older adults, non-Hispanic whites, and those with higher education and income. Individuals with MASLD had a higher prevalence of total CVD than those without MASLD, even after adjusting for socioeconomic and metabolic factors. These differences were more pronounced in younger age groups. Conclusions: This study revealed a doubled 30-year trend in CVD prevalence among adults with MASLD in the US. Sociodemographic disparities emphasize the need for tailored screening, prevention, and policy measures to address gaps and promote cardiovascular health in this population.

Steatotic liver diseases (SLD) have become more prevalent over the last decade and are associated not only with cardiometabolic diseases but also with psychological symptoms (depression, fatigue). These symptoms are also common in post-COVID syndrome (PCS). Therefore, the aim of the study was to analyze the burden of SLD in PCS patients.

We systematically screened all PCS patients from our post-COVID outpatient clinic using transient elastography, structured questionnaires for neurocognitive evaluation and blood sample analysis. Controls without PCS and without known liver diseases were also recruited and assessed with the same approach.

560 PCS patients and 103 healthy controls were included. The overall prevalence of SLD was high in both cohorts (57 vs. 53%). PCS patients with SLD were more frequently male (41 vs. 24%), older (52 vs. 44 years) and had more cardiometabolic diseases (87.0 vs. 46.4%). Cognitive impairment was more related to SLD in PCS patients than in the no-SLD group (OR: 1.68, CI: 1.14-2.46, p = 0.008). The presence of SLD was related to severe COVID-19 with hospitalization (OR: 2.91, CI: 1.85-4.56, p < 0.001). Within 1 year of the follow-up, 152 of 289 patients described a resolution in PCS irrespective of the presence or absence of SLD (log-rank p = 0.96).

SLD is associated with severe COVID-19 and cognitive dysfunction in PCS. Longitudinal studies are needed to assess the role of hepatic steatosis, development of post-acute infection regulation (e.g., SARS-CoV-2) and to differentiate between SLD-associated symptoms and PCS.

The relationship between the serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) and cardiovascular disease (CVD) risk in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) is unknown. This study aims to investigate the relationship between UHR and cardiovascular disease risk in patients with MAFLD.

Data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2017-2020, in which 3289 patients with MAFLD participated. Participants were grouped according to their 10-year cardiovascular disease risk level, which was assessed by the Framingham Risk Score (FRS). We used binary logistic regression to analyze the relationship between UHR and CVD risk and smoothed curve-fitting models and threshold effect analyses to describe the relationship between UHR and CVD risk scores.

After adjusting for all confounders, individuals with high UHR exhibited a higher prevalence of intermediate/high risk by FRS [odds ratio (OR): 2.12, 95% confidence interval (CI): (1.34, 3.35), P = 0.001]. UHR was nonlinear positive correlated with FRS (log-likelihood ratio test < 0.001). And there was a breakpoint of 364.38 and an apparent threshold effect. When UHR was lower than 364.38, The FRS increased with increasing UHR (P < 0.0001), whereas when UHR was higher than 364.38, the relationship between FRS and UHR was statistically insignificant (P = 0.0964).

The UHR was significantly associated with a 10-year risk of cardiovascular disease in patients with MAFLD. Higher UHR was associated with higher FRS in patients with MAFLD. The UHR can be a valid biomarker for predicting the 10-year risk of cardiovascular disease in patients with MAFLD.

The utility of CT-derived parameters for hepatic steatosis assessment has primarily focused on non-alcoholic fatty liver disease. This study aimed to evaluate their applicability in chronic hepatitis B (CHB) through a retrospective analysis of 243 CHB patients. Using deep-learning-based 3D organ segmentation on abdominal CT scans at 100 kVp, the mean volumetric CT attenuation of the liver and spleen was automatically measured on pre-contrast (liver (L)_pre and spleen (S)_pre) and post-contrast (L_post and S_post) portal venous phase images. To identify mild, moderate, and severe steatosis (S1, S2, and S3 based on the controlled attenuation parameter), L_pre showed areas under the receiver operating characteristic curve (AUROCs) of 0.695, 0.779, and 0.795, significantly higher than L-S_pre (0.633, 0.691, and 0.732; Ps = 0.02, 0.003, and 0.03). Post-contrast parameters demonstrated slightly lower AUROCs than their pre-contrast counterparts (Ps = 0.15-0.81). Concomitant hepatic fibrosis influenced diagnostic performance, with CT parameters performing better in patients without severe fibrosis than those with (F3-4 on transient elastography), though statistical significance was only observed for L-S_post in severe steatosis (P = 0.037). In conclusion, CT attenuation-based parameters extracted through automated 3D analysis show promise as a tool for assessing hepatic steatosis in patients with CHB.

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) among individuals with hyperuricemia is significantly high. The aim of this study was to identify effective biomarkers for the detection of MASLD among patients with hyperuricemia.

We conducted an analysis involving 3424 participants with hyperuricemia from the National Health and Nutrition Examination Survey (1999-2020). To identify potential significant variables, we employed Boruta's algorithm, SHapley Additive exPlanations (SHAP) and random forests. Multivariable logistic regression models were utilized to assess the odds ratio (OR) of developing MASLD. To evaluate the accuracy and clinical value of our prediction model, we employed receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves.

Among the study population of 3424 participants (mean [SD] age, 54 [20] years, 1788 [52.22%] males) with hyperuricemia, 1670 participants had MASLD. Using Boruta's algorithm, SHAP and random forests, our analysis suggested that Triglyceride Glucose-Waist Circumference (TyG_WC) was one of the most significant variables in predicting MASLD risk, with an area under the receiver operating characteristic (AUROC) of 0.865. The restricted curve spline (RCS) revealed a positive association between the odds ratio of TyG_WC and MASLD, when compared with lowest quantile of TyG_WC, the risk of MASLD for highest quantile was 137.96 times higher. The predictive strategy incorporating TyG_WC notably enhanced the clinical model, with threshold probabilities spanning from approximately 0% to 100%, resulting in a significant improvement of the net benefit.

Our analysis found that TyG_WC was one of the most significant variables in predicting MASLD risk among individuals with hyperuricemia.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment. The guidelines aim to advance clinical practice, knowledge, and research on MAFLD, particularly in special groups. The guidelines are designed to advance clinical practice, to provide evidence-based recommendations to assist healthcare stakeholders in decision-making and to improve patient care and disease awareness. The guidelines take into account the burden of clinical management for the healthcare sector.