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This study aimed to investigate the relationship between liver stiffness measurements (LSM), controlled attenuation parameter (CAP), and coronary heart disease (CHD) using data from the National Health and Nutrition Examination Survey (NHANES). A total of 12,684 American populations who underwent health examinations were included from the NHANES database spanning 2017–2020 (pre-pandemic) and 2021–2023. Logistic regression was employed to analyze the associations between LSM, CAP, and CHD. Restricted cubic spline (RCS) regression was used to evaluate the dose–response relationship between LSM, CAP, and CHD. Stratified analyses were performed according to age, sex, race, education level, income, BMI, blood pressure, hepatitis B surface antibody, and cholesterol to explore potential interactions and identify specific subpopulations at risk. Finally, predictive models were developed using logistic regression, decision trees, XGBoost classifiers, and neural networks to assess the predictive value of LSM and CAP for CHD risk. During the study period, 12,684 participants were included, of whom 539 (4.24%) were diagnosed with CHD. After adjusting for confounders, both LSM and CAP were found to be significantly positively associated with CHD risk in U.S. adults. Subgroup analyses revealed a significant positive association between LSM and CHD incidence in participants stratified by race and blood parameters (interaction P -value < 0.050). Additionally, sex, age, and lipid profiles showed a significant positive correlation between CAP and CHD risk. Predictive models also indicated a positive relationship between LSM, CAP, and CHD risk. Both LSM and CAP were nonlinearly and positively associated with CHD risk, highlighting the importance of maintaining lower levels of liver stiffness and fat as a potential preventive strategy for CHD.

According to the increasing need for accurate staging of hepatic fibrosis, the ultrasound (US) elastography techniques have evolved significantly over the past two decades. Currently, US elastography is increasingly used in clinical practice. Previously published studies have demonstrated the excellent diagnostic performance of US elastography for the detection and staging of liver fibrosis. Although US elastography may seem easy to perform and interpret, there are many technical and clinical factors which can affect the results of US elastography. Therefore, clinicians who are involved with US elastography should be aware of these factors. The purpose of this article is to present a brief overview of US techniques with the relevant technology, the clinical indications, diagnostic performance, and technical and biological factors which should be considered in order to avoid misinterpretation of US elastography results.

Objective: Liver stiffness (LS) values are known to be associated with increased right ventricle (RV) pressure in patients with heart failure (HF). The aim of this study was to determine the changes in LS in patients of different New York Heart Association (NYHA) classes and the parameters related to increased LS in HF patients with reduced ejection fraction (HFrEF). Methods: A total of 181 patients with HFrEF were included in the study. Routine anamnesis, physical examination, laboratory examinations and echocardiography were performed. The LS measurement was performed using the ElastPQ technique. The patients were grouped by NYHA class I-IV. Results: The LS values were significantly different between NYHA class groups, increasing significantly from NYHA class I to IV. The number of patients with LS >7 kPa or >10.6 kPa was significantly greater among the class III-IV patients. The RV myocardial performance index, tricuspid regurgitation pressure gradient, N-terminal pro b-type natriuretic peptide, and aspartate aminotransferase levels were found to be independently associated with LS. It was also observed that LS independently determined III-IV classification and that an increase of 1 kPa increased the risk of being class III-IV by 94.4%. Receiver operating characteristic analysis with a cut-off value of 7 kPa for LS identified patients with class III-IV disease with 82.8% sensitivity and 81.8% specificity. Conclusion: In HFrEF, the LS value increased with NYHA class and independently determined patients with class III-IV disease. A higher LS value independently determined increased RV pressure and systolic functions.

Aims/hypothesisLiraglutide, a daily injectable glucagon-like peptide-1 receptor (GLP-1r) agonist, has been shown to reduce liver fat content (LFC) in humans. Data regarding the effect of dulaglutide, a once-weekly GLP-1r agonist, on human LFC are scarce. This study examined the effect of dulaglutide on LFC in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).MethodsEffect of dulaglutide on liver fat (D-LIFT) was a 24 week, open-label, parallel-group, randomised controlled trial to determine the effect of dulaglutide on liver fat at a tertiary care centre in India. Adults (n = 64), who had type 2 diabetes and MRI-derived proton density fat fraction-assessed LFC of ≥6.0% at baseline, were randomly assigned to receive dulaglutide weekly for 24 weeks (add-on to usual care) or usual care, based on a predefined computer-generated number with a 1:1 allocation that was concealed using serially numbered, opaque, sealed envelopes. The primary endpoint was the difference of the change in LFC from 0 (baseline) to 24 weeks between groups. The secondary outcome measures included the difference of the change in pancreatic fat content (PFC), change in liver stiffness measurement (LSM in kPa) measured by vibration-controlled transient elastography, and change in liver enzymes.ResultsEighty-eight patients were screened; 32 were randomly assigned to the dulaglutide group and 32 to the control group. Overall, 52 participants were included for per-protocol analysis: those who had MRI-PDFF data at baseline and week 24. Dulaglutide treatment resulted in a control-corrected absolute change in LFC of −3.5% (95% CI −6.6, −0.4; p = 0.025) and relative change of −26.4% (−44.2, −8.6; p = 0.004), corresponding to a 2.6-fold greater reduction. Dulaglutide-treated participants also showed a significant reduction in γ-glutamyl transpeptidase (GGT) levels (mean between-group difference −13.1 U/l [95% CI −24.4, −1.8]; p = 0.025) and non-significant reductions in aspartate aminotransferase (AST) (−9.3 U/l [−19.5, 1.0]; p = 0.075) and alanine aminotransferase (ALT) levels (−13.1 U/l [−24.4, 2.5]; p = 0.10). Absolute changes in PFC (−1.4% [−3.2, 0.3]; p = 0.106) and LSM (−1.31 kPa [−2.99, 0.37]; p = 0.123) were not significant when comparing the two groups. There were no serious drug-related adverse events.Conclusions/interpretationWhen included in the standard treatment for type 2 diabetes, dulaglutide significantly reduces LFC and improves GGT levels in participants with NAFLD. There were non-significant reductions in PFC, liver stiffness, serum AST and serum ALT levels. Dulaglutide could be considered for the early treatment of NAFLD in patients with type 2 diabetes.Trial registrationClinicalTrials.gov NCT03590626FundingThe current study was supported by an investigator-initiated study grant from Medanta–The Medicity’s departmental research fund and a grant from the Endocrine and Diabetes Foundation (EDF), India.Graphical abstract

Background：To compare the diagnostic values of magnetic resonance elastography （MRE） and diffusion-weighted imaging （DWI） in staging hepatic fibrosis （HF） in an animal model.Methods：This study consisted of 44 rabbits served as HF group and 9 normal rabbits.HF group was divided into two subgroups：Group A （n =32） and Group B （n =12）.Rabbits in Group B were served as a complementary group when rabbits in Group A suddenly died during the study.Rabbits from control and Group A underwent abdominal MR imaging （MRI）,MRE,and DWI.In Group A,random eight rabbits underwent MRI examinations at 4,5,6,l0 weeks after carbon tetrachloride oil subcutaneous injection.Liver stiffness （LS） and apparent diffusion coefficient （ADC） values of liver parenchyma were measured.The diagnostic performance of MRE and DWI for staging HF was compared using the receiver operating characteristic curve analysis on the basis of the histopathological analysis of HF.Results：Significant differences of LS and DWI values were present among HF stages （P 〈 0.005）.The LS values measured on MRE （r =0.838,P 〈 0.001） were more strongly correlated with the HF stages than with ADC values （r =-0.527,P 〈 0.001）.The area under the receiver operating characteristic curve values of LS were significantly larger than those of DWI were for discriminating two stages of HF （0.979 vs.0.712 for ≥ S 1,0.922 vs.0.699 for ≥ S2）.MRE showed higher specificity for predicting all stages of HF compared to DWI.Conclusions：MRE more strongly correlated with the HF stages than DWI and is more specific in predicting all HF stages.

An increasing percentage of people have or are at risk to develop non-alcoholic fatty liver disease (NAFLD) worldwide. NAFLD comprises different stadia going from isolated steatosis to non-alcoholic steatohepatitis (NASH). NASH is a chronic state of liver inflammation that leads to the transformation of hepatic stellate cells to myofibroblasts. These cells produce extra-cellular matrix that results in liver fibrosis. In a normal situation, fibrogenesis is a wound healing process that preserves tissue integrity. However, sustained and progressive fibrosis can become pathogenic. This process takes many years and is often asymptomatic. Therefore, patients usually present themselves with end-stage liver disease e.g., liver cirrhosis, decompensated liver disease or even hepatocellular carcinoma. Fibrosis has also been identified as the most important predictor of prognosis in patients with NAFLD. Currently, only a minority of patients with liver fibrosis are identified to be at risk and hence referred for treatment. This is not only because the disease is largely asymptomatic, but also due to the fact that currently liver biopsy is still the golden standard for accurate detection of liver fibrosis. However, performing a liver biopsy harbors some risks and requires resources and expertise, hence is not applicable in every clinical setting and is unsuitable for screening. Consequently, different non-invasive diagnostic tools, mainly based on analysis of blood or other specimens or based on imaging have been developed or are in development. In this review, we will first give an overview of the pathogenic mechanisms of the evolution from isolated steatosis to fibrosis. This serves as the basis for the subsequent discussion of the current and future diagnostic biomarkers and anti-fibrotic drugs.

Objective To develop and validate a nomogram based on liver stiffness (LS) for predicting symptomatic post-hepatectomy (PHLF) in patients with hepatocellular carcinoma (HCC). Methods A total of 266 patients with HCC were enrolled prospectively from three tertiary referral hospitals from August 2018 to April 2021. All patients underwent preoperative laboratory examination to obtain parameters of liver function. Two-dimensional shear wave elastography (2D-SWE) was performed to measure LS. Three-dimensional virtual resection obtained the different volumes including future liver remnant (FLR). A nomogram was developed by using logistic regression and determined by receiver operating characteristic (ROC) curve analysis and calibration curve analysis, which was validated internally and externally. Results A nomogram was constructed with the following variables: FLR ratio (FLR of total liver volume), LS greater than 9.5 kPa, Child–Pugh grade, and the presence of clinically significant portal hypertension (CSPH). This nomogram enabled differentiation of symptomatic PHLF in the derivation cohort (area under curve [AUC], 0.915), internal fivefold cross-validation (mean AUC, 0.918), internal validation cohort (AUC, 0.876) and external validation cohort (AUC, 0.845). The nomogram also showed good calibration in the derivation, internal validation, and external validation cohorts (Hosmer–Lemeshow goodness-of-fit test , p  = 0.641, p  = 0.06, and p  = 0.127, respectively). Accordingly, the safe limit of the FLR ratio was stratified using the nomogram. Conclusion An elevated level of LS was associated with the occurrence of symptomatic PHLF in HCC. A preoperative nomogram integrating LS, clinical and volumetric features was useful in predicting postoperative outcomes in patients with HCC, which might help surgeons in the management of HCC resection. Clinical relevance statement A serial of the safe limit of the future liver remnant was proposed by a preoperative nomogram for hepatocellular carcinoma, which might help surgeons in ‘how much remnant is enough in liver resection’. Key Points • An elevated liver stiffness with the best cutoff value of 9.5 kPa was associated with the occurrence of symptomatic post-hepatectomy liver failure in hepatocellular carcinoma. • A nomogram based on both quality (Child–Pugh grade, liver stiffness, and portal hypertension) and quantity of future liver remnant was developed to predict symptomatic post-hepatectomy liver failure for HCC, which enabled good discrimination and calibration in both derivation and validation cohorts. • The safe limit of future liver remnant volume was stratified using the proposed nomogram, which might help surgeons in the management of HCC resection.

BackgroundLiver stiffness measurement (LSM) has been used to measure fibrosis in patients with various types of chronic liver diseases. However, its usefulness as a screening procedure in apparently healthy people had not been evaluated to date.Methods1358 subjects >45 years old from a general population attending for a medical check-up were consecutively enrolled in the study. All subjects were submitted to medical examination and laboratory tests in addition to LSM, performed on the same day by a single operator. Subjects with LSM values >8 kPa were referred to a liver unit for further investigations.Results168 subjects were not considered for analysis due to missing data (n=23), LSM failure (n=51) or unreliable LSM values (n=94). Among the 1190 remaining subjects, 89 (7.5%) had LSM >8 kPa including nine patients with LSM >13 kPa. Despite the fact that normal liver tests were observed in 43% of them (38 out of 89), a specific cause of chronic liver disease was found in all cases. Non-alcoholic fatty liver disease (NAFLD) was the likely cause of chronic liver disease in 52 patients, alcoholic liver disease (ALD) in 20, and both causes were associated in seven additional patients. Hepatitis C virus and hepatitis B virus chronic hepatitis was documented in five and four cases, respectively, and primary biliary cirrhosis in one. Liver biopsy was obtained for 27 patients, including the nine patients with LSM >13 kPa, who were diagnosed with liver cirrhosis due to ALD (n=5), chronic hepatitis C (n=3) or chronic hepatitis B (n=1). The 18 remaining biopsies showed liver fibrosis in all cases except one (isolated steatosis), with ALD and NAFLD being present in six and eight cases, respectively.ConclusionLSM proved to be a useful and specific procedure to screen for cirrhosis in the general population and to detect undiagnosed chronic liver disease in apparently healthy subjects.

BackgroundThe prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with liver fibrosis. We aimed to investigate whether liver stiffness measurement (LSM) and changes in LSM (ΔLSM) on magnetic resonance elastography (MRE) can predict clinical events in patients with MASLD.MethodsWe included 405 patients with MASLD who underwent at least two MREs. The patients were divided into five groups corresponding to fibrosis stages (0–4) based on initial LSM and classified as progressors (ΔLSM ≥ 19%) or non-progressors (ΔLSM < 19%) based on the difference between the first and last LSM.ResultsThe mean follow-up period was 72.6 months, and the mean interval between MREs was 23.5 months. There were 52 (12.8%) progressors and 353 (87.2%) non-progressors. The initial LSM was significantly associated with the cumulative probabilities of decompensated cirrhosis, hepatocellular carcinoma (HCC), liver-related events, extrahepatic malignancies, and overall mortality but not with cardiovascular disease. Progressors had significantly higher hazard ratios (HRs) for decompensated cirrhosis, HCC, and liver-related events but not for extrahepatic malignancies, cardiovascular disease, or overall mortality. Among patients without cirrhosis, the HR for developing cirrhosis among progressors was 60.15. Progressors had a significantly higher risk of liver-related events, even in the low initial LSM (fibrosis stage 0–2) subgroups.ConclusionsBoth initial LSM and ΔLSM can predict liver-related events in patients with MASLD, even for low initial LSM. This integrated assessment can allow more detailed risk stratification compared with single LSM assessments and identify high-risk patients with MASLD among those previously considered as low risk.

INTRODUCTION:Steatotic liver disease is common in people with HIV (PWH). Identifying those with advanced fibrosis (AF, bridging fibrosis or cirrhosis), F3-4, is important. We aimed to examine the performance of FIB-4 and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) in PWH to identify those with AF assessed by liver stiffness measurement (LSM).METHODS:We prospectively collected data on adults participating in 2 National Institute of Health-sponsored HIV NAFLD networks. All had HIV on antiretroviral therapy (ART) ≥6 months with HIV RNA <200 copies/mL. Those with viral hepatitis, other liver disease, excessive alcohol use, or hepatic decompensation were excluded. Vibration-controlled transient elastrography for LSM was performed, and AF defined as ≥11 kPa was compared with FIB-4 and NFS at predefined thresholds (<1.3 and >2.67 for FIB-4 and <−1.455 and >0.675 for NFS).RESULTS:A total of 1,065 participants were analyzed: mean age 51.6 years, 74% male, 28% White, 46% Black, 22% Hispanic, with 34% overweight (body mass index 25-29 kg/m2) and 43% obese (body mass index ≥30 kg/m2). Features of the metabolic syndrome were common: hyperlipidemia 35%, type 2 diabetes 17%, and hypertension 48%. The median CD4+ T-cell count was 666 cells/mm3, 74% had undetectable HIV RNA, and duration of HIV-1 was 17 years with most taking a nucleoside reverse transcriptase inhibitor (92%) and an integrase inhibitor (83%). The mean LSM was 6.3 kPa, and 6.3% had AF. The area under the receiver characteristic curve for FIB-4 and NFS to identify AF were 0.70 and 0.75, respectively. While both had high negative predictive values (97%-98%), the sensitivity at low thresholds and specificity at high thresholds were 64% and 97% for FIB-4 and 80% and 96% for NFS, respectively. Neither FIB-4 nor NFS at either threshold had good positive predictive value to detect AF.DISCUSSION:FIB-4 and NFS have excellent specificity and negative predictive value for detecting AF, and thus can be used as screening tools in PWH to exclude those with AF who do not need further testing (LSM) or referral to hepatologist.