Vibration Controlled Transient Elastography Based Parameters Predicts Clinical Outcomes in Liver Transplant Recipients.

BACKGROUND & AIMS: Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk stratify liver transplant (LT) recipients, however, there is currently little data demonstrating the relationship between VCTE and clinical outcomes. METHODS: 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) ≥10.5kPa 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. RESULTS: The LSM was elevated in 64 (18%) and CAP in 163 (45%) of LT recipients. The baseline LSM values were similar in patients with elevated vs. normal CAP values. After a median follow up of 65 (IQR 20, 140) months from LT to baseline VCTE, 66 (18%) of patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (HR 1.97, 95% CI 1.11, 3.50, p=0.02) and new onset cirrhosis (HR 6.74, 95% CI 2.08, 21.79, p<0.01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow up with HR 4.14 [95% CI 1.29, 13.27, p=0.017]. CONCLUSIONS: 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.

Serum Mac-2 binding protein glycosylation isomer dynamics in patients achieving sustained virologic response for hepatitis C virus.

BACKGROUND AND AIM: Understanding the dynamics of serum Mac-2 binding protein glycosylation isomer (M2BPGi) remains pivotal for hepatitis C virus (HCV) patients' post-sustained virologic response (SVR12) through direct-acting antivirals (DAAs). METHODS: We compared areas under receiver operating characteristic curves (AUROCs) of M2BPGi, FIB-4, and APRI and assess M2BPGi cutoff levels in predicting fibrosis stages of ≥F3 and F4 utilizing transient elastography in 638 patients. Variations in M2BPGi levels from pretreatment to SVR12 and their association with pretreatment alanine transaminase (ALT) levels and fibrosis stage were investigated. RESULTS: The AUROCs of M2BPGi were comparable to FIB-4 in predicting ≥F3 (0.914 vs 0.902, P = 0.48) and F4 (0.947 vs 0.915, P = 0.05) but were superior to APRI in predicting ≥F3 (0.914 vs 0.851, P = 0.001) and F4 (0.947 vs 0.857, P < 0.001). Using M2BPGi cutoff values of 2.83 and 3.98, fibrosis stages of ≥F3 and F4 were confirmed with a positive likelihood ratio ≥10. The median M2BPGi change was -0.55. Patients with ALT levels ≥5 times ULN or ≥F3 demonstrated more pronounced median decreases in M2BPGi level compared to those with ALT levels 2-5 times ULN and <2 times ULN (-0.97 vs -0.68 and -0.44; P < 0.001) or with < F3 (-1.52 vs -0.44; P < 0.001). CONCLUSIONS: Serum M2BPGi is a reliable marker for advanced hepatic fibrosis. Following viral clearance, there is a notable M2BPGi decrease, with the extent of reduction influenced by ALT levels and fibrosis stage.

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

BACKGROUND: Obesity 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. METHODS: Data 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. RESULTS: A 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. CONCLUSIONS: Different 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (ß = 1.86, 95% CI 0.53-3.17) but not with CAP (ß = 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. CONCLUSIONS: 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.

Changes in Transient Elastography with Glucagon-Like Peptide-1 Receptor Agonist Use in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Real-World Retrospective Analysis.

Introduction: Current guidelines recommend the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD), especially in patients with comorbid diabetes and obesity. This study investigated the effects of GLP-1RAs on hepatic steatosis and fibrosis in patients with MASLD, as measured by changes in vibration-controlled transient elastography (VCTE) and other clinical parameters in a real-world clinical setting. Methods: We conducted a single-center, retrospective analysis of 96 patients with MASLD from a multidisciplinary care clinic who completed VCTE at baseline and follow-up within 6-24 months to compare changes in controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as well as other metabolic markers, between GLP-1RA users and nonusers using two-sample t-tests and Wilcoxon rank-sum tests. We also assessed whether improvements in hepatic steatosis, defined as a change in CAP >38 dB/m as previously described in the literature, were associated with improvement in fibrosis. Results: GLP-1RA use resulted in significant improvements in weight (-8.1 kg vs. -3.5 kg, P = 0.009), body mass index (BMI) (-2.9 kg/m2 vs. -1.3 kg/m2, P = 0.012), alanine aminotransferase (-15.0 IU/L vs. -4.0 IU/L, P = 0.017), aspartate aminotransferase (-5.0 IU/L vs. -1.0 IU/L, P = 0.021), glycated hemoglobin (HbA1c) (-0.7% vs. 0.1%, P = 0.019), and CAP (-59.9 dB/m vs. -29.1 dB/m, P = 0.016). Responders also had significant improvements in weight (-9.2 kg vs. -1.9 kg, P < 0.001), BMI (-3.3 kg/m2 vs. -0.7 kg/m2, P < 0.001), diastolic blood pressure (-6.1 mmHg vs. -0.7 mmHg, P = 0.028), HbA1c (-0.8% vs. 0.3%, P < 0.001), and LSM (-1.5 kPa vs. 0.1 kPa, P < 0.001). Conclusions: Patients with MASLD treated with GLP-1RAs showed significant improvements in hepatic steatosis and multiple other metabolic parameters, with weight loss as the proposed mechanism for this liver improvement. In addition, change in CAP >38 dB/m was associated with improvements in LSM and other metabolic parameters, suggesting the clinical utility of VCTE in the surveillance of MASLD.

Adipose Tissue Insulin Resistance Correlates with Disease Severity in Pediatric Metabolic Dysfunction-associated Steatotic Liver Disease: A Prospective Cohort Study.

OBJECTIVES: To assess the role of adipose tissue insulin resistance (Adipo-IR) in the pathogenesis of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and to determine Adipo-IR evolution during a lifestyle intervention program. STUDY DESIGN: In this prospective, cohort study, children and adolescents with severe obesity were recruited between July 2020 and December 2022 at an inpatient pediatric rehabilitation center. Treatment consisted of dietary intervention and physical activity. Liver steatosis and fibrosis were evaluated using ultrasound and transient elastography with controlled attenuation parameter and liver stiffness measurement. Every 4 to 6 months, anthropometric measurements, serum biochemical analysis, ultrasound and elastography were repeated. Adipo-IR was estimated by the product of the fasting serum insulin times the fasting free fatty acid concentration and hepatic IR by the homeostatic model assessment for insulin resistance (HOMA-IR), respectively. RESULTS: 56% of 200 patients with obesity had evidence of steatosis on ultrasound and 26% were diagnosed with fibrosis (≥F2). Adipo-IR increased progressively from lean controls to patients with obesity to patients with MASLD and MASLD with fibrosis. Adipo-IR was already elevated in patients with only mild steatosis (p = 0.0403). Patients with more insulin-sensitive adipose tissue exhibited lower liver fat content (p < 0.05) and serum alanine transaminase levels (p = 0.001). Adipo-IR correlated positively with visceral adipose tissue weight, waist circumference, and the visceral adipose tissue/gynoid adipose tissue ratio (p < 0.001), but not with total body fat percentage (p = 0.263). After 4 to 6 months of lifestyle management, both MASLD and Adipo-IR improved. CONCLUSIONS: Our data suggest that Adipo-IR is associated with the presence of pediatric MASLD, particularly steatosis.

Noninvasive Assessment of Portal Hypertension.

The progressive use of noninvasive tests (NITs) has changed the way hepatologists diagnose and manage patients with chronic liver disease, mainly because of their easiness to use and the ability to be repeated during follow-up. Liver stiffness measurement is the NIT with more scientific evidence. NITs have demonstrated to be useful to detect not only liver fibrosis but also the presence of clinically significant portal hypertension. Moreover, current evidence supports they can also be useful to evaluate the prognosis of patients with chronic liver disease.

FibroScan® versus Biochemical Scores: A Study of Liver Fibrosis in HIV with HBV Co-Infection.

The study aimed to determine liver fibrosis in human immunodeficiency virus (HIV) positive individuals using transient elastography (FibroScan®), Fibrosis-4 (FIB-4) score, and aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) in the HIV Department from Infectious Diseases Hospital "Victor Babeș" Craiova, Romania. Of the analyzed HIV-positive subjects (n = 161), 93 (57.76%) had HIV mono-infection, and 68 (42.24%) had Hepatitis B Virus (HBV) co-infection. The prevalence of advanced liver fibrosis was higher (F2: 11.76% and F3: 13.24%, F4: 4.41%) in the HIV-HBV co-infected group compared to the HIV mono-infected group. The univariate and multivariate analysis identified HBV co-infection (OR = 5.73) male sex (OR = 5.34), serum aspartate amino-transferase levels (Pearson's rho = 0.273), low platelet count (Pearson's rho = -0.149) and erythrocyte sedimentation rate (OR = 1.030) as risk factors for the presence of liver fibrosis. Body mass index (OR = 1.08), serum lipid levels (OR = 0.96), viral load at diagnosis (OR = 1.00005), and low CD4+ cell count (OR = 0.977) were also correlated with liver fibrosis. The FIB-4 and APRI scores were strongly correlated with each other. In conclusion, HBV co-infection seems to be a determinant factor for liver fibrosis development in people living with HIV, together with other risk factors.

The Link between Abdominal Obesity Indices and the Progression of Liver Fibrosis: Insights from a Population-Based Study.

There is currently no available information on the correlation between abdominal obesity indices and the risk of liver fibrosis progression. We aimed to investigate the relationship between the body mass index (BMI), waist circumference (WC), and the visceral adiposity index (VAI) with the progression of liver fibrosis. The study also evaluated the association between these indices and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. A total of 1403 subjects participated in the cross-sectional and longitudinal population-based study. Liver stiffness was assessed via transient elastography, at baseline and follow-up (median: 4.2 years). The subgroup with dysglycemia was also analyzed. In the cross-sectional study, the highest quartile of VAI, BMI ≥ 30 kg/m2, and abdominal obesity showed significant associations with the prevalence of MASLD and liver fibrosis, as well as with fibrosis progression. However, VAI showed no association with MASLD incidence. Among the dysglycemic subjects, there was no observed association between VAI and the incidence of MASLD or the progression of fibrosis. In conclusion, the BMI, WC, and the VAI are associated with an increased risk of progression to moderate-to-advanced liver fibrosis in the general population. However, the VAI does not perform better than the BMI and WC measurement.

Lower FIB-4 threshold in patients with diabetes improves diagnostic accuracy of the test in a Hispanic population.

Background: Non-invasive tests (NITs) can be used to estimate the severity of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) but their diagnostic accuracy is variable. Hispanic patients are at increased risk of NAFLD and diabetes. We evaluate the diagnostic performance of the fibrosis index based on 4 factors (FIB-4) in a population of Hispanic patients who underwent vibration-controlled transient elastography (VCTE). Methods: A total of 1,524 patients underwent VCTE at University of California, Los Angeles from July 18, 2019 to June 7, 2022. Ultimately 110 patients were identified as Hispanic, with confirmed NAFLD. Sensitivity, specificity, positive predictive value and negative predictive value of FIB-4 threshold ≥1.3 were calculated. Logistic regression models were used to determine updated thresholds for patients with and without diabetes based on Youden's index. Results: Of the 110 patients, the majority (65%) were female. Prevalence of diabetes was higher in the group with clinically significant fibrosis (76% vs. 36%, P<0.001). Using a FIB-4 threshold ≥1.3 to predict clinically significant fibrosis (F2-F4 on VCTE), area under the receiver operating characteristic (AUROC) was 0.74. By incorporating diabetes status, AUROC was 0.81 when employing a FIB-4 threshold of ≥1.0 in patients with diabetes and ≥1.5 in patients without diabetes. Conclusions: Using a FIB-4 threshold of ≥1.0 in patients with diabetes and ≥1.5 in patients without diabetes improves the diagnostic performance of the test. The new FIB-4 including diabetes status will lead to improved screening in patients who are at risk of clinically significant fibrosis.

Impact of an Automated Population-Level Cirrhosis Screening Program Using Common Pathology Tests on Rates of Cirrhosis Diagnosis and Linkage to Specialist Care (CAPRISE): Protocol for a Pilot Prospective Single-Arm Intervention Study.

BACKGROUND: People with compensated cirrhosis receive the greatest benefit from risk factor modification and prevention programs to reduce liver decompensation and improve early liver cancer detection. Blood-based liver fibrosis algorithms such as the Aspartate Transaminase-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) index are calculated using routinely ordered blood tests and are effective screening tests to exclude cirrhosis in people with chronic liver disease, triaging the need for further investigations to confirm cirrhosis and linkage to specialist care. OBJECTIVE: This pilot study aims to evaluate the impact of a population screening program for liver cirrhosis (CAPRISE [Cirrhosis Automated APRI and FIB-4 Screening Evaluation]), which uses automated APRI and FIB-4 calculation and reporting on routinely ordered blood tests, on monthly rates of referral for transient elastography, cirrhosis diagnosis, and linkage to specialist care. METHODS: We have partnered with a large pathology service in Victoria, Australia, to pilot a population-level liver cirrhosis screening package, which comprises (1) automated calculation and reporting of APRI and FIB-4 on routinely ordered blood tests; (2) provision of brief information about liver cirrhosis; and (3) a web link for transient elastography referral. APRI and FIB-4 will be prospectively calculated on all community-ordered pathology results in adults attending a single pathology service. This single-center, prospective, single-arm, pre-post study will compare the monthly rates of transient elastography (FibroScan) referral, liver cirrhosis diagnosis, and the proportion linked to specialist care in the 6 months after intervention to the 6 months prior to the intervention. RESULTS: As of January 2024, in the preintervention phase of this study, a total of 120,972 tests were performed by the laboratory. Of these tests, 78,947 (65.3%) tests were excluded, with the remaining 42,025 (34.7%) tests on 37,872 individuals meeting inclusion criteria with APRI and FIB-4 being able to be calculated. Of these 42,025 tests, 1.3% (n=531) had elevated APRI>1 occurring in 446 individuals, and 2.3% (n=985) had elevated FIB-4>2.67 occurring in 816 individuals. Linking these data with FibroScan referral and appointment attendance is ongoing and will continue during the intervention phase, which is expected to commence on February 1, 2024. CONCLUSIONS: We will determine the feasibility and effectiveness of automated APRI and FIB-4 reporting on the monthly rate of transient elastography referrals, liver cirrhosis diagnosis, and linkage to specialist care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000295640; https://tinyurl.com/58dv9ypp. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56607.

WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.

Ultrasonographic Assessment of Tissue Stiffness: Recent Progress in Transient Elastography and Shear Wave Elastography in the Liver and Various Organs.

Ultrasonography is a noninvasive and widely accessible modality in clinical practice. Recently, ultrasonography has been used to evaluate tissue stiffness; the two representative techniques are transient elastography (FibroScan®) and shear wave elastography. These modalities are now generally used for the assessment of liver fibrosis, the prediction of hepatocarcinogenesis, and determining prognosis. In addition, shear wave elastography is available, not only for the liver but also for various other organs, including the breast and brain. In the breast and brain, shear wave elastography distinguishes malignant lesions from benign ones. Moreover, shear wave elastography can be useful for differentiating between ischemic and hemorrhagic strokes. This review summarizes the recent progress in transient elastography and shear wave elastography of the liver and introduces the advantages of ultrasonographic assessment of tissue stiffness in various organs, including the breast, brain, kidney, heart, thyroid, pancreas, muscle, and bone.

Management of Portal Hypertension in the Older Patient.

PURPOSE OF THIS REVIEW: Aging is a process of physiological slowing, reduced regenerative capacity and inability to maintain cellular homeostasis. World Health Organisation declared the commencement of population aging globally, largely attributed to improvement in the healthcare system with early diagnosis and effective clinical management. Liver ages similar to other organs, with reduction in size and blood flow. In this review we aim to evaluate the effect of aging in liver disease. RECENT FINDINGS: Aging causes dysregulation of major carbohydrate, fat and protein metabolism in the liver. Age is a major risk factor for liver fibrosis accelerated by sinusoidal endothelial dysfunction and immunological disharmony. Age plays a major role in patients with liver cirrhosis and influence outcomes in patients with portal hypertension. Transient elastography may be an useful tool in the assessment of portal hypertension. Hepatic structural distortion, increased vascular resistance, state of chronic inflammation, associated comorbidities, lack of physiological reserve in the older population may aggravate portal hypertension in patients with liver cirrhosis and may result in pronounced variceal bleed. Cut-offs for other non-invasive markers of fibrosis may differ in the elderly population. Non-selective beta blockers initiated at lower dose followed by escalation are the first line of therapy in elderly patients with cirrhosis and portal hypertension, unless contraindicated. Acute variceal bleed in the elderly cirrhotic patients can be life threatening and may cause rapid exsanguination due to poor reserve and associated comorbidities. Vasoactive drugs may be associated with more adverse reactions. Early endoscopy may be warranted in the elderly patients with acute variceal bleed. Role of TIPS in the elderly cirrhotics discussed. Management of portal hypertension in the older population may pose significant challenges to the treating clinician.

Gender Differences in Liver Steatosis and Fibrosis in Overweight and Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease before and after 8 Weeks of Very Low-Calorie Ketogenic Diet.

Obesity and metabolic syndrome are linked to steatotic liver disease (SLD), the most common form of chronic liver disease. Lifestyle modifications and dieting are strategies that can prevent metabolic dysfunction-associated steatotic liver disease (MASLD). The very low-calorie ketogenic diet (VLCKD) is a helpful treatment for MASLD and has been recommended for people affected by obesity; we evaluated the effect of gender on steatosis and fibrosis in a cohort of 112 overweight or obese patients undergoing an eight-week treatment with a VLCKD. Differences between the genders in terms of anthropometric measures, body composition, and metabolic indicators were examined before, during, and after the nutritional intervention. At baseline, there were significant differences between men and women in terms of anthropometric parameters, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting insulin, hepatic markers, and lipid profile. Men had considerably higher levels of liver steatosis (measured by CAP) and liver stiffness (measured by E) under basal conditions than women. After the VLCKD, there were reductions in both genders of controlled attenuation parameter (CAP), body weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, insulin resistance, fat mass (FM), free fat mass (FFM), and fasting blood glucose, insulin, glycated hemoglobin (HbA1c), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, alanine transaminase (ALT), gamma-glutamyl transferase (γGT), and uric acid levels. Only in men, liver stiffness, aspartate aminotransferase (AST), creatinine, and C-reactive protein (CRP) levels significantly decreased. Moreover, men had significantly greater levels of liver steatosis: the male gender featured an increase of 23.96 points of the Fibroscan CAP. Men exhibited higher levels of steatosis and fibrosis than women, and these differences persist despite VLCKD. These gender-specific variations in steatosis and fibrosis levels could be caused by hormonal and metabolic factors, suggesting that different therapeutic strategies might be required depending on the gender.

A study of the relationship between serum asprosin levels and MAFLD in a population undergoing physical examination.

Asprosin, an adipokine, was recently discovered in 2016. Here, the correlation between asprosin and metabolic-associated fatty liver disease (MAFLD) was examined by quantitatively assessing hepatic steatosis using transient elastography and controlled attenuation parameter (CAP). According to body mass index (BMI), 1276 adult participants were enrolled and categorized into three groups: normal, overweight, and obese. The study collected and evaluated serum asprosin levels, general biochemical indices, liver stiffness measure, and CAP via statistical analysis. In both overweight and obese groups, serum asprosin and CAP were greater than in the normal group (p < 0.01). Each group showed a positive correlation of CAP with asprosin (p < 0.01). The normal group demonstrated a significant and independent positive relationship of CAP with BMI, low-density lipoprotein cholesterol (LDL-C), asprosin, waist circumference (WC), and triglycerides (TG; p < 0.05). CAP showed an independent positive association (p < 0.05) with BMI, WC, asprosin, fasting blood glucose (FBG), and TG in the overweight group, and with high-density lipoprotein cholesterol (HDL-C) showed an independent negative link (p < 0.01). CAP showed an independent positive relationship (p < 0.05) with BMI, WC, asprosin, TG, LDL-C, FBG, glycated hemoglobin A1c (HbA1c), and alanine transferase in the obese group. CAP also showed an independent positive link (p < 0.01) with BMI, WC, asprosin, TG, LDL-C, and FBG in all participants while independently and negatively correlated (p < 0.01) with HDL-C. Since asprosin and MAFLD are closely related and asprosin is an independent CAP effector, it may offer a novel treatment option for metabolic diseases and MAFLD.

Association between blood chromium and hepatic steatosis assessed by liver ultrasound transient elastography: National Health and Nutrition Examination Survey 2017-2020.

Background: Hepatic steatosis is a significant pathological feature of fatty liver disease (FLD) which is widely spread with no effective treatment available. Previous studies suggest that chromium (Cr) intake reduces lipid deposition in the liver in animals. However, the connection between blood Cr and hepatic steatosis among humans remains inconclusive. Methods: Using the data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020, we performed a cross-sectional analysis, including 4,926 participants. The controlled attenuation parameter (CAP) measured by the vibration controlled transient elastography (VCTE) was used to evaluate the degree of liver steatosis. Weighted univariate regression, multivariate linear regression, smooth fitting curves and subgroup analysis were used. In addition, we carried out trend tests, multiple interpolations, and interaction analyses to conduct sensitivity analyses. Results: After adjusting with various covariables, multivariate linear regression analysis demonstrated a significant negative correlation between blood Cr and CAP [ß (95% CI) = -5.62 (-11.02, -0.21)]. The negative correlation between blood Cr and CAP was more significant in the males, 50-59 years, overweight, hypercholesterolemia, HDL-C ≥ 65 mg/dL, HbA1c (5.70-6.10 %), HOMA-IR (0.12-2.76), total bilirubin (0.30-0.40 mg/dL), ever alcohol consumption subjects. Of note, the relationships between blood Cr and CAP followed a U-shaped curve in the smokers and non-smokers, with blood Cr thresholds of 0.48, 0.69 µg/L, respectively. Conclusions: There is an independently negative correlation between blood Cr and hepatic steatosis in American. Our study provides clinical researchers with a new insight into the prospective prevention of hepatic steatosis.

The evaluation of non-alcoholic fatty liver disease in children with obesity with vibration-controlled transient elastography.

INTRODUCTION: Parallel to the worldwide increase in obesity, the epidemic of chronic liver disease is increasing also in pediatric population. Our aim is to provide a different outlook on the current screening confusion in pediatric non-alcoholic fatty liver disease (NAFLD) with the non-invasive vibration-controlled transient elastography (VCTE) method. MATERIALS AND METHODS: This single-center, cross-sectional, comparative study was performed at the tertiary center, included 95 patients with obesity and 116 controls, both groups were 9-18 years of ages. VCTE examinations performed in all patients. The cut-off values for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were established by comparing the study and control groups. RESULTS: The cut-off for CAP was determined as >236 dB/m when comparing the two groups. The AUC was 0.900 (95% CI, 0.851-0.937) and the diagnostic accuracy was 77.9% and 91.4% for sensitivity and specificity, respectively. The cut-off value for LSM >5 kPa was determined by comparison of the two groups. The AUC was 0.794 (95% CI, 0.733-0.846) and the diagnostic accuracies were 50.5% and 90.5% for sensitivity and specificity, respectively. CONCLUSIONS: There is no benchmark method for screening pediatric NAFLD. However, VCTE is a promising method for screening pediatric NAFLD. It is accessible, repeatable and practical.

A Simple and Reliable 2D-Shear Wave Elastography and UltraSound Coefficient Attenuation Parameter Technique in Chronic Liver Diseases.

BACKGROUND: The performance and reliability criteria for Aixplorer MACH30 (SS) in chronic liver diseases (CLD) have not been validated. AIMS: The objectives were to define the optimal procedure, the accuracy for fibrosis and steatosis diagnosis, and the reliability criteria using SS. METHODS: Patients had 2D-shear wave elastography (SWE) and ultraSound-guided controlled attenuation parameter (SCAP) performed in triplicate at the mid-axillary line (MAL), posterior axillary line (PAL), and anterior axillary line (AAL). Performances of SWE and SCAP were defined using transient elastography (TE ≥ 9.5 kPa) and CAP (≥ 275 dB/m) using Fibroscan (FS) as reference and validated with liver biopsy (LB). RESULTS: FS and SS data from 203 CLD patients were analyzed (55 ± 14 years; 59% male; MASLD 58%). Median TE and CAP were 6.4 kPa (2.5-66.9) and 270 dB/m (141-400). The best technique for the diagnosis of advanced fibrosis and significant steatosis was the median of three SWE values and three SCAP values at MAL, PAL, and AAL with an AUROC of 0.96 [95% CI 0.93-0.98] and 0.91 [95% CI 0.86-0.95]. Only skin-to-liver distance ≥ 2.4 cm (p = 0.012, 95% CI 1.37-13.38) was independently associated with discordance. The accuracy of SWE (≥ 8.5 kPa) and SCAP (≥ 0.44) was analyzed in 58 patients with LB. The PPV and NPV were 50% and 94%, and 71% and 88% for fibrosis and steatosis, respectively. CONCLUSION: A reliable diagnosis of advanced fibrosis and significant steatosis can be obtained with the median of three measurements in different liver portions using SS. The only non-reliable criterion is skin-to-liver distance ≥ 2.4 cm.

CTLA-4 haplotype predicts HBsAg and HBcrAg levels and HBeAg seroconversion age in children with chronic HBV infection.

Background & Aim: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between CTLA-4 genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection. Methods: We recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the CTLA-4 gene single nucleotide polymorphisms rs4553808 (-A1661G)/rs5742909 (-C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort. Results: CTLA-4 promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the CTLA-4 AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; p = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 vs. 0.03 log10 IU/ml/year, p = 0.02). The CTLA-4 AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (p = 0.01). Conclusions: Chronic HBV-infected patients with a CTLA-4 AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion. Impact and implications: The role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that CTLA-4 haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.