Controlled Attenuation Parameter Research Articles

The association between vitamin E intake and hepatic steatosis in general and obese populations

PurposeUsing data from the National Health and Nutrition Examination Survey (NHANES) and employing Controlled Attenuation Parameter (CAP) measures, this study explores the correlation between vitamin E (VE) intake and hepatic steatosis and its impact on different subsets.Materials and methodsWe selected 5757 participants with CAP data from the 2017–2020 NHANES dataset. Daily VE intake was assessed by a 24-hour dietary recall. Hepatic fat content was quantified using transient elastography to measure CAP. Stratified multivariable regression analysis investigated relationships in different subsets, and a generalized additive model identified nonlinear relationships and thresholds.ResultsAfter adjusting for confounders, higher VE intake correlated with lower CAP levels. Subgroup analyses and tests for interaction revealed a significantly stronger negative correlation between VE intake and CAP in obese individuals. Further analysis indicated a curvilinear relationship between VE intake and the severity of liver fat degeneration in both the general study population and the obese subgroup, demonstrating a threshold effect. In the general population, VE intake below the threshold (6.58 mg/day) is positively correlated with CAP levels, whereas intake above this threshold shows a negative correlation. For obese individuals, the threshold is set at 7.37 mg/day, above which the negative correlation with CAP is even more pronounced.ConclusionOur study revealed a negative correlation between VE intake and hepatic fat content, highlighting the potentially crucial role VE plays in obese fatty liver patients. Importantly, we identified threshold effects of VE intake in both general and obese populations. Our results support clinical nutritional interventions, personalized dietary guidance, and the development of drugs to combat fatty liver.

Rapid improvement of hepatic steatosis and liver stiffness after metabolic/bariatric surgery: a prospective study

Metabolic dysfunction-associated steatotic liver disease (MASLD) and related steatohepatitis (MASH) are common among obese patients and may improve after metabolic/bariatric surgery (MBS). 93 Patients undergoing MBS in 2021–2022 were prospectively enrolled. Liver stiffness measurement (LSM; via vibration-controlled transient elastography [VCTE], point [pSWE] and 2D [2DSWE] shear wave elastography) and non-invasive steatosis assessment (via controlled attenuation parameter [CAP]) were performed before (baseline [BL]) and three months (M3) after surgery. 93 patients (median age 40.9 years, 68.8% female, median BL-BMI: 46.0 kg/m2) were included. BL-liver biopsy showed MASLD in 82.8% and MASH in 34.4% of patients. At M3 the median relative total weight loss (%TWL) was 20.1% and the median BMI was 36.1 kg/m2. LSM assessed by VCTE and 2DSWE, as well as median CAP all decreased significantly from BL to M3 both in the overall cohort and among patients with MASH. There was a decrease from BL to M3 in median levels of ALT (34.0 U/L to 31 U/L; p = 0.025), gamma glutamyl transferase (BL: 30.0 to 21.0 U/L; p < 0.001) and MASLD fibrosis score (BL: − 0.97 to − 1.74; p < 0.001). Decreasing LSM and CAP, as well as liver injury markers suggest an improvement of MASLD/MASH as early as 3 months after MBS.

The relationship between the systemic immune inflammation index and the nonalcoholic fatty liver disease in American adolescents

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known.MethodsWe collected data from the National Health and Nutrition Examination Survey 2017–2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD.ResultsA total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092–11.249, P < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD (p < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases.ConclusionThere was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD.

Association between composite dietary antioxidant index and metabolic dysfunction associated steatotic liver disease: result from NHANES, 2017-2020.

The development of metabolic dysfunction associated steatotic liver disease (MASLD) has been associated with lipid accumulation, oxidative stress, endoplasmic reticulum stress, and lipotoxicity. The Composite Dietary Antioxidant Index (CDAI) is a comprehensive score representing an individual intake of various dietary antioxidants, including vitamin A, vitamin C, vitamin E, selenium, zinc, and carotenoids. This study investigated the association between CDAI and MASLD. Clinical and demographic data, as well as ultrasound transient elastography measurements at baseline, were collected from the National Health and Nutrition Examination Survey 2017-2020 (NHANES 2017-2020). The controlled attenuation parameter was utilized to diagnose the presence of hepatic steatosis and to categorize individuals into those with and without MASLD. Liver stiffness was measured by ultrasound transient elastography, and subjects were classified as those with and without advanced liver fibrosis. This study included 5,884 adults, of whom 3,433 were diagnosed with MASLD, resulting in a weighted prevalence of 57.3%. After adjusting for covariates, the odds ratios for MASLD were 0.96 (95% CI: 0.82, 1.12) in the second quartile, 0.80 (95% CI: 0.68, 0.95) in the third quartile and 0.60 (95% CI: 0.49, 0.73) in the fourth quartile, respectively. CDAI, however, was not significantly associated with advanced liver fibrosis. These findings suggested that scores on the CDAI were linearly and negatively associated with the prevalence of MASLD in the United States adults.

Urinary Equol and Equol-Predicting Microbial Genera Are Favorably Associated with Body Fat Measures among Chinese Adults

BackgroundMany studies have investigated the intake of dietary isoflavones in relation to obesity risk, whereas the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at the population level remain to be fully characterized. ObjectivesWe aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. MethodsIn this 1-y longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1 y. Liver fat [indicated by the controlled attenuation parameter (CAP)] and other body composition were also measured after 1 y. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. ResultsAmong 305 participants (median age: 50 y, IQR, 37–59 y) including 138 males and 167 females, higher urinary excretion of equol was associated with lower CAP (β = −0.013, P < 0.001) and body fat mass (β= −0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P > 0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (β = −0.040, P = 0.011). ConclusionsHigh urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.

Material deprivation is associated with liver stiffness and liver-related outcomes in people with HIV.

Socioeconomic status (SES) is a driver of health disparities and chronic diseases. People with HIV (PWH) are at risk for chronic liver diseases. We evaluated the association between low SES and hepatic outcomes in PWH. We included PWH from a prospective cohort. SES was assessed by the Pampalon material and social deprivation index to classify the cohort into quintiles of deprivation. Multivariable linear regression was used to investigate associations of material and social deprivation with liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) as markers of hepatic fibrosis and steatosis, respectively. Incidence of outcomes was evaluated through survival analysis. Among the 804 PWH included, 45% and 72% were living in areas of the highest material and social deprivation, respectively. Materially deprived PWH were more frequently female and of non-white ethnicity and had higher prevalence of metabolic comorbidities. After adjustments, material deprivation correlated with increased LSM (β = 1.86, 95% CI 0.53-3.17) but not with CAP (β = 6.47, 95% CI -5.55-18.49). Patients were observed for a median follow-up of 3.8 years. Incidence of liver-related events was higher in most materially deprived compared to most privileged PWH (hazard ratio 3.03, 95% CI 1.03-8.92), while there was no difference in extrahepatic outcomes or all-cause mortality. Social deprivation showed no association with either LSM or clinical outcomes. Living in materially deprived neighbourhoods as a proxy for lower SES, is associated with LSM and liver-related events in PWH. Future strategies should explore mechanisms underlying these relationships and whether enhanced material security improves hepatic outcomes.

Six-month supplementation with high dose coenzyme Q10 improves liver steatosis, endothelial, vascular and myocardial function in patients with metabolic-dysfunction associated steatotic liver disease: a randomized double-blind, placebo-controlled trial

BackroundMetabolic-dysfunction Associated Steatotic Liver Disease (MASLD) has been associated with increased cardiovascular risk. The aim of this Randomized Double-blind clinical Trial was to evaluate the effects of coenzyme-Q10 supplementation in patients with MASLD in terms of endothelial, vascular and myocardial function.MethodsSixty patients with MASLD were randomized to receive daily 240 mg of coenzyme-Q10 or placebo. At baseline and at 6-months, the a)Perfused boundary region of sublingual vessels using the Sideview Darkfield imaging technique, b)pulse-wave-velocity, c)flow-mediated dilation of the brachial artery, d)left ventricular global longitudinal strain, e)coronary flow reserve of the left anterior descending coronary artery and f)controlled attenuation parameter for the quantification of liver steatosis were evaluated.ResultsSix months post-treatment, patients under coenzyme-Q10 showed reduced Perfused boundary region (2.18 ± 0.23vs.2.29 ± 0.18 μm), pulse-wave-velocity (9.5 ± 2vs.10.2 ± 2.3 m/s), controlled attenuation parameter (280.9 ± 33.4vs.304.8 ± 37.4dB/m), and increased flow-mediated dilation (6.1 ± 3.8vs.4.3 ± 2.8%), global longitudinal strain (-19.6 ± 1.6vs.-18.8 ± 1.9%) and coronary flow reserve (3.1 ± 0.4vs.2.8 ± 0.4) compared to baseline (p < 0.05). The placebo group exhibited no improvement during the 6-month follow-up period (p > 0.05). In patients under coenzyme-Q10, the reduction in controlled attenuation parameter score was positively related to the reduction in Perfused boundary region and pulse wave velocity and reversely related to the increase in coronary flow reserve and flow-mediated dilation (p < 0.05 for all relations).ConclusionsSix-month treatment with high-dose coenzyme-Q10 reduces liver steatosis and improves endothelial, vascular and left ventricle myocardial function in patients with MASLD, demonstrating significant improvements in micro- and macro-vasculature function.Trial RegistrationNCT05941910

Association between different obesity patterns and the risk of NAFLD detected by transient elastography: a cross-sectional study

BackgroundObesity has become a major global public health challenge. Studies examining the associations between different obesity patterns and the risk of nonalcoholic fatty liver disease (NAFLD) are limited. This study aimed to investigate the relationships between different obesity patterns and the risk of NAFLD in a large male population in the US.MethodsData from the 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) were utilized. Liver steatosis and fibrosis were assessed with FibroScan using the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM). Steatosis was identified with a CAP value of 248 dB/m or higher. Abdominal obesity was defined by a waist circumference (WC) of 102 cm or more for males and 88 cm or more for females. Overweight was defined as a body mass index (BMI) of 24.0 kg/m2 and above. General obesity was identified with a BMI of 28.0 kg/m2 or higher. Obesity status was categorized into four types: overweight, general obesity, abdominal obesity, and combined obesity. Multivariate logistic regression, adjusting for potential confounders, was used to examine the link between obesity patterns and NAFLD risk. Subgroup analysis further explored these associations.ResultsA total of 5,858 adults were included. After multivariable adjustment, compared to the normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for NAFLD in individuals with overweight, general obesity, abdominal obesity, and combined obesity were 6.90 [3.74–12.70], 2.84 [2.38–3.39], 3.02 [2.02–4.51], and 9.53 [7.79–11.64], respectively. Subgroup analysis showed the effect of different obesity patterns on NAFLD risk was stable among individuals with different clinical conditions. In the fully adjusted multivariate logistic regression model, WC was positively associated with NAFLD risk (OR: 1.48; 95% CI: 1.42–1.53; P < 0.001). WC also demonstrated strong discriminatory ability for NAFLD in Receiver Operating Characteristic (ROC) analysis, achieving an Area Under the Curve (AUC) of 0.802.ConclusionsDifferent patterns of obesity are risk factors for NAFLD. An increase in WC significantly increased NAFLD risk. More attention should be paid to preventing different patterns of obesity among adults.

The correlation between hepatic controlled attenuation parameter (CAP) value and insulin resistance (IR) was stronger than that between body mass index, visceral fat area and IR

BackgroundHepatic controlled attenuation parameter (CAP) is a novel marker for quantifying hepatic fat accumulation. Insulin resistance (IR) plays a major role in the pathogenesis and natural history of hepatic steatosis. This study aimed to investigate the possible relationship between CAP value and IR.MethodsThis study included a total of 420 patients with overweight or obesity who came to the obesity clinic at Tianjin Union Medical Center. Vibration-controlled transient elastography examination was conducted to detect CAP and liver stiffness measurement (LSM) values. Body composition, including visceral fat area (VFA), and body fat mass (BFM), was evaluated by the direct segmental multi-frequency bioelectrical impedance analysis (BIA). The associations between CAP value, body mass index (BMI), VFA, BFM and homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed.ResultsCAP value was positively associated with HOMA-IR (r = 0.568, P < 0.001), the strength of which was much stronger than BMI, VFA, and BFM. In multivariate linear regression, CAP value and HOMA-IR showed a significant positive association (adjusted β = 0.015, 95% CI 0.007–0.022, P < 0.001). Subgroup analysis suggested no significant interaction between CAP value and HOMA-IR across age, BMI, LSM, hypertension, and sex groups (all P for interaction > 0.05).ConclusionsHepatic CAP value is more remarkably than other obesity markers associated with HOMA-IR in individuals with overweight or obesity, regardless of age, BMI, LSM, hypertension, and sex.

Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases

Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases

Comparing similarities and differences between NAFLD, MAFLD, and MASLD in the general U.S. population.

Recently, the multisociety Delphi consensus renamed non-alcoholic fatty liver disease (NAFLD) terminology [previously renamed metabolic-associated fatty liver disease (MAFLD)] as metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to compare the similarities and differences between NAFLD, MAFLD, and MASLD and to clarify the impact of this new name change. A cross-sectional study of 3,035 general subjects with valid vibration-controlled transient elastography data was conducted based on data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. NAFLD, MAFLD, and MASLD were defined according to the corresponding consensus criteria. Using controlled attenuation parameter (CAP) ≥274 dB/m and liver stiffness measurements (LSM) ≥9.7 kPa as the cutoff values for the presence of hepatic steatosis and advanced liver fibrosis (ALF), the prevalence of NAFLD, MAFLD, and MASLD were 38.01% (95% CI 35.78-40.29%), 41.09% (39.09-43.12%), and 37.9% (35.70-40.14%), respectively, and the corresponding prevalence of ALF was 10.21% (7.09-14.48%), 10.13% (7.06-14.35%), and 10.24% (7.11-14.53%), respectively. The kappa values for the three definitions were above 0.9. The prevalence and severity of the three definitions remained similar when the sensitivity analyses were performed using different CAP thresholds. The prevalence of NAFLD, MAFLD, MASLD, and ALF increased as the number of cardiometabolic risk factors (CMRF) increased. Our findings highlight the consistency among the three definitions, especially between NAFLD and MASLD, so that the new consensus will not disturb the original NAFLD-related findings. Additionally, more attention should be paid to patients with a high number of CMRFs.

Vibration-Controlled Transient Elastography–Based Parameters Predict Clinical Outcomes in Liver Transplant Recipients

Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk-stratify liver transplant (LT) recipients; however, there are currently little data demonstrating the relationship between VCTE and clinical outcomes. A total of 362 adult LT recipients with successful VCTE examination between 2015 and 2022 were included. Presence of advanced fibrosis was defined as liver stiffness measurement (LSM) ≥10.5 kPa and hepatic steatosis as controlled attenuation parameter (CAP) ≥270 dB/m. The outcomes of interest included all-cause mortality, myocardial infarction (MI), and graft cirrhosis using cumulative incidence analysis that accounted for the competing risks of these outcomes. The LSM was elevated in 64 (18%) and CAP in 163 (45%) LT recipients. The baseline LSM values were similar in patients with elevated vs normal CAP values. After a median follow-up of 65 (interquartile range, 20-140) months from LT to baseline VCTE, 66 (18%) patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.11-3.50; P= .02) and new onset cirrhosis (HR, 6.74; 95% CI, 2.08-21.79; P < .01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow-up (HR, 4.14; 95% CI, 1.29-13.27; P= .017). The VCTE-based parameters are associated with clinical outcomes and offer the potential to be incorporated into clinical risk-stratification strategies to improve outcomes among LT recipients.

Correlation between controlled attenuation parameter values with SYNTAX score in patients with significant coronary artery disease

Non-alcoholic fatty liver disease (NAFLD) is an emerging cause of chronic liver disease, with coronary artery disease (CAD) as the main cause of death in NAFLD patients. However, correlation between the severity of liver steatosis and coronary atherosclerosis is yet to be understood. Here we aim to explore the correlation between controlled attenuation parameter (CAP) values and SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score in adult patients with significant CAD, defined as ≥ 50% stenosis of the left main coronary artery, or ≥ 70% stenosis of the other major coronary arteries. A cross-sectional study was conducted on 124 adult patients with significant CAD who underwent coronary angiography. Transient elastography with CAP was used to assess liver steatosis severity, resulting in a mean CAP value of 256.5 ± 47.3 dB/m, with 52.5% subjects had significant steatosis (CAP value of ≥ 248 dB/m). Median SYNTAX score was 22. A statistically significant correlation was observed between CAP value and SYNTAX score (r = 0.245, p < 0.0001). The correlation was more pronounced in patients with prior history of PCI (r = 0.389, p = 0.037). Patients with high-risk SYNTAX score (> 32) had the highest CAP value (285.4 ± 42.6 dB/m), and it was significantly higher than those with low-risk SYNTAX score (0–22), with a mean difference of 38.76 dB/m (p = 0.006). Patients with significant liver steatosis should undergo periodic CAD assessment and lifestyle modification, especially those with severe liver steatosis.

Predicting of Hepatic Steatosis in Living Liver Donor via CT Liver Attenuation Index (LAI) and Fibroscan Controlled Attenuation Parameter (CAP) Correlation with Biopsy Result

Abstract Background The most prevalent persistent parenchymatous liver alterations in healthy individuals are thought to be hepatic steatosis. The liver biopsy is the most crucial procedure for the identification and measurement of hepatic steatosis. By identifying the liver attenuation index (LAI) at an unenhanced CT image, hepatic steatosis can be evaluated without the risk of liver resection. Objective Using liver biopsy histological analysis as a reference standard, to examine the precision of the CT liver attenuation index (LAI) and fibroscan controlled attenuation parameter (CAP) for quantitative evaluation of macro vesicular steatosis in living related liver donors. Methods In this study comparing CT liver attenuation index &amp; fibroscan controlled attenuation parameter with liver pathology of steatosis in subject's candidate for liver living donors 50 subjects in each two study's correlation with biopsy results, conducted at Ain Shams Shams Specialized hospital and other Private hospitals over about 2 years. Results Our study reported that liver – spleen attenuation index of 9 is the cutoff value with sensitivity 100% and specificity 80% that make it a very good method to exclude donor to have steatosis ≥15%, which mean if donor had LS index &amp;lt; 9 we can safely do proceed do liver biopsy. Our study reported that CAP measurement had an AUROC OF 0.780, for detecting steatosis ≥ 15 %, with sensitivity is only 60% with specificity as CT LAI of 80%, which consider low compared to other study, that could be due to small number of donors in out study with steatosis ≥ 15 % (5 case from 50 donors) unlike the other studies. Conclusion When used to estimate the amount of liver fat in liver donors, the examined CAP and CT indices worked equally. But according to multivariate analysis, the only factor strongly linked with hepatic steatosis in alive donors was the CT L-S attenuation index. We contend that the combination of CT L-S attenuation index and CAP allows for the detection of the degree of hepatic steatosis and can be used as an option to liver biopsy, reserving liver biopsy for those with positive steatosis donors.

Dietary and circulating branched chain amino acids are unfavorably associated with body fat measures among Chinese adults

Animal studies showed a detrimental effect of dietary branched chain amino acids (BCAAs) on metabolic health, while epidemiological evidence on dietary BCAAs and obesity is limited and inconclusive. We hypothesized that high dietary and circulating BCAAs are unfavorably associated with obesity in community-dwelling adults. We evaluated the 1-year longitudinal associations of dietary BCAA intake and circulating BCAAs with body fat measures. Body weight, height, and circumferences of the waist (WC) and hip (HC) were measured at baseline and again after 1-year. Body composition and liver fat [indicated by controlled attenuation parameter (CAP)] were also assessed after 1-year. Serum BCAA concentrations at baseline were quantified by liquid chromatography mass spectrometry. Diet was collected using 4 quarterly 3-day recalls during the 1-year. The correlation coefficients between dietary and serum BCAAs were 0.12 (P = .035) for total dietary BCAAs, and ranged from -0.02 (soy foods, P = .749) to 0.18 (poultry, P = .001). Total dietary BCAA intake was associated with increase in body weight (β = 0.044, P = .022) and body mass index (BMI, β = 0.047, P = .043). BCAAs from animal foods were associated with increase in HC, while BCAAs from soy foods were associated with weight gain and higher CAP (all P < .05). Serum BCAAs were associated with higher WC, HC, BMI, body fat mass, visceral fat level, and CAP (all P < .05). These results support that dietary and circulating BCAAs are positively associated with the risk of obesity. More cohort studies with validated dietary assessment tools and long-term follow-up among diverse populations are needed to confirm our findings.

Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease

Both metabolic dysfunction and alcohol consumption cause steatotic liver disease (SLD). The distinction between metabolic dysfunction-associated SLD (MASLD) and MetALD categories is based on arbitrary thresholds of alcohol intake. Thus, we assessed the impact of different levels of alcohol consumption on SLD severity and their interaction with metabolic comorbidities. We performed a population-based study with transient elastography (FibroScan®) data from participants in Spain (derivation cohort) and the US (validation cohort). A controlled attenuation parameter ≥275dB/m was used to define SLD. At least one cardiometabolic risk factor was required to define MASLD. Among patients with MASLD, low alcohol consumption was defined as an average of 5-9 drinks/week, moderate consumption as 10-13 drinks/week for females and 10-20 drinks/week for males, and increased alcohol intake (MetALD) as 14-35 drinks/week for females and 21-42 drinks/week for males. Significant fibrosis was defined as a liver stiffness measurement ≥8kPa and at-risk metabolic dysfunction-associated steatohepatitis (MASH) as a FAST score ≥0.35. The derivation cohort included 2,227 individuals with MASLD (9% reported low, 14% moderate alcohol consumption) and 76 cases with MetALD. Overall prevalences of significant fibrosis and at-risk MASH were 7.6% and 14.8%, respectively. In the multivariable analysis, alcohol consumption was independently associated with significant fibrosis and at-risk MASH. A dose-dependent increase in the prevalence of significant fibrosis and at-risk MASH was observed between the number of drinks/week and the number of cardiometabolic factors. The validation cohort included 1,732 participants with MASLD, of whom 17% had significant fibrosis and 13% at-risk MASH. This cohort validated the association between moderate intake and MASLD at risk of progression (odds ratio 1.69, 95% CI 1.06-2.71). Moderate alcohol intake is commonly seen in MASLD and increases the risk of advanced disease to a level similar to that observed in MetALD. Metabolic risk factors such as overweight, diabetes or dyslipidemia, and alcohol consumption can cause liver disease. These factors frequently coexist, but their joint effects on liver fibrosis remain uncertain. In this study, we have analyzed individuals from the general population with MASLD (metabolic dysfunction-associated steatotic liver disease) enrolled in Spain and the US. We show that moderate alcohol consumption has a supra-additive effect with metabolic risk factors, exponentially increasing the risk of liver fibrosis. These results suggest that there are no safe limits of daily alcohol intake in patients with unhealthy metabolic status and MASLD.

Association of Aortic Stiffness and Pressure Pulsatility With Noninvasive Estimates of Hepatic Steatosis and Fibrosis: The Framingham Heart Study.

Arterial stiffening may contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease. We aimed to assess relations of vascular hemodynamic measures with measures of hepatic steatosis and fibrosis in the community. Our sample was drawn from the Framingham Offspring, New Offspring Spouse, Third Generation, Omni-1, and Omni-2 cohorts (N=3875; mean age, 56 years; 54% women). We used vibration-controlled transient elastography to assess controlled attenuation parameter and liver stiffness measurements as measures of liver steatosis and liver fibrosis, respectively. We assessed noninvasive vascular hemodynamics using arterial tonometry. We assessed cross-sectional relations of vascular hemodynamic measures with continuous and dichotomous measures of hepatic steatosis and fibrosis using multivariable linear and logistic regression. In multivariable models adjusting for cardiometabolic risk factors, higher carotid-femoral pulse wave velocity (estimated β per SD, 0.05 [95% CI, 0.01-0.09]; P=0.003), but not forward pressure wave amplitude and central pulse pressure, was associated with more liver steatosis (higher controlled attenuation parameter). Additionally, higher carotid-femoral pulse wave velocity (β=0.11 [95% CI, 0.07-0.15]; P<0.001), forward pressure wave amplitude (β=0.05 [95% CI, 0.01-0.09]; P=0.01), and central pulse pressure (β=0.05 [95% CI, 0.01-0.09]; P=0.01) were associated with more hepatic fibrosis (higher liver stiffness measurement). Associations were more prominent among men and among participants with obesity, diabetes, and metabolic syndrome (interaction P values, <0.001-0.04). Higher carotid-femoral pulse wave velocity, but not forward pressure wave amplitude and central pulse pressure, was associated with higher odds of hepatic steatosis (odds ratio, 1.16 [95% CI, 1.02-1.31]; P=0.02) and fibrosis (odds ratio, 1.40 [95% CI, 1.19-1.64]; P<0.001). Elevated aortic stiffness and pressure pulsatility may contribute to hepatic steatosis and fibrosis.

LIVERSTAT for risk stratification for patients with metabolic dysfunction-associated fatty liver disease.

LIVERSTAT is an artificial intelligence-based noninvasive test devised to screen for and provide risk stratification for metabolic dysfunction-associated fatty liver disease (MAFLD) by using simple blood biomarkers and anthropometric measurements. We aimed to study LIVERSTAT in patients with MAFLD and to explore its role for the diagnosis of advanced fibrosis. This is a retrospective study of data from MAFLD patients who underwent a liver biopsy. Patients with type 2 diabetes who underwent transient elastography and had liver stiffness measurement (LSM)<5kPa were included as patients with no fibrosis. Among these patients, controlled attenuation parameter <248dB/m was considered as no steatosis. The LIVERSTAT results were generated based on a proprietary algorithm, blinded to the histological and LSM data. The data for 350 patients were analyzed (mean age 53years, 45% male, advanced fibrosis 22%). The sensitivity, specificity, positive predictive value, negative predictive value, and misclassification rate of LIVERSTAT to diagnose advanced fibrosis were 90%, 50%, 30%, 95%, and 42%, respectively. The corresponding rates for Fibrosis-4 score (FIB4) were 56%, 83%, 44%, 89%, and 22%, respectively. When LSM was used as a second test, the corresponding rates for LIVERSTAT were 60%, 97%, 76%, 94%, and 8%, respectively, while the corresponding rates for FIB4 were 38%, 99%, 83%, 89%, and 11%, respectively. LIVERSTAT had a higher negative predictive value compared with FIB4 and a lower misclassification rate compared with FIB4 when used in a two-step approach in combination with LSM for the diagnosis of advanced fibrosis.

Semaglutide Concurrently Improves Vascular and Liver Indices in Patients With Type 2 Diabetes and Fatty Liver Disease.

The cardiovascular benefits of semaglutide are established; however, its effects on surrogate vascular markers and liver function are not known. To investigate the effects of semaglutide on vascular, endothelial, and liver function in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). Overall, 75 consecutive subjects with T2DM and NAFLD were enrolled: 50 patients received semaglutide 1 mg (treatment group) and 25 patients received dipeptidyl peptidase 4 inhibitors (control group). All patients underwent a clinical, vascular, and hepatic examination with Fibroscan elastography at 4 and 12 months after inclusion in the study. Treatment with semaglutide resulted in a reduction of Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, Fibrosis-4 (FIB-4) score and perfused boundary region (PBR) at 4 and at 12 months (P < .05), contrary to controls. Patients treated with semaglutide showed a greater decrease of central systolic blood pressure (SBP) (-6% vs -4%, P = .048 and -11% vs -9%, P = .039), augmentation index (AIx) (-59% vs -52%, P = .041 and -70% vs -57%, P = .022), and pulse wave velocity (PWV) (-6% vs -3.5%, P = .019 and -12% vs -10%, P = .036) at 4 and at 12 months, respectively. In all patients, ΔPWV and ΔPBR were correlated with a corresponding reduction of CAP, E fibrosis, NAFLD fibrosis, and FIB-4 scores. Twelve-month treatment with semaglutide simultaneously improves arterial stiffness, endothelial function, and liver steatosis and fibrosis in patients with T2DM and NAFLD.

Potential Drawbacks of Noninvasive Diagnostic Methods for Nonalcoholic Fatty Liver Disease.

The rising obesity epidemic is a phenomenon that has gained increasing attention from health providers and health policy makers. This led to recognition of nonalcoholic fatty liver disease (MASLD). The standard for its assessment has been histologic, which is neither practical nor acceptable by patients. Subsequently, a number of noninvasive assessment methods have been developed. However, despite ease of implementation, their confounding variables do hinder their accuracy. Nonetheless, the development of the liver stiffness measurement (LSM) and incorporation of other biological parameters has minimized but not eliminated the need for liver biopsy. Imaging methods are useful in evaluation, estimation, and following the progression of steatosis and fibrosis with particular attention to controlled attenuation parameter (CAP) and MRI-Proton Density Fat Fraction (MRI-PDFF). The choices for the family physician are broad and rely on tests' availability, cost, and patient acceptance. Great efforts have been undertaken to produce more robust and novel noninvasive markers that indicate fibrinogenesis directly in an implementable and cost-effective way.