Liver Stiffness Measurement Research Articles

Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306).

Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvedilol-treating cohort. In the meta-analysis with six studies (n = 819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new "CSPH risk" model. In the HVPG cohort (n = 151), the new model accurately predicted CSPH with cutoff values of 0 and -0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n = 1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <-0.68 (low-risk), -0.68 to 0 (medium-risk), and >0 (high-risk). In the carvedilol-treated cohort, patients with high-risk CSPH treated with carvedilol (n = 81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n = 613 before propensity score matching [PSM], n = 162 after PSM). Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

The Early On-treatment Stiffness Decline Attributed to the Improved Hepatic Inflammation in Fibrotic Chronic Hepatitis B.

Hepatic inflammation, the driver of fibrosis progression in liver disease, can impact the accuracy of liver stiffness measurement (LSM). We wondered whether the decline in LSM value during the early antiviral phase was mainly attributed to the control of hepatic inflammation or the regression of fibrosis in patients with fibrotic/cirrhotic chronic hepatitis B (CHB). The study cohort was composed of 82 patients with CHB who underwent antiviral and antifibrotic therapy at the Fifth Medical Center of PLA General Hospital. All patients had liver biopsies at both baseline and 72 weeks posttherapy. Liver pathology and clinical data, including the LSM value, were collected. After 72 weeks of treatment, both the histologic activity index score and fibrosis score, as well as the LSM value, were significantly decreased (P < 0.001), compared with their baseline values. The pretreatment correlation of LSM value with either histologic activity index score (r = 0.526 vs r = 0.286) or fibrosis score (r = 0.677 vs r = 0.587) was attenuated at 72 weeks. Notably, logistic regression analysis revealed that the improvement in inflammation (odds ratio = 1.018, 95% CI: 1.002-1.031, P = 0.023) but not fibrosis (odds ratio = 0.994, 95% CI: 0.980-1.009, P = 0.414), had an impact on the change in LSM values between baseline and at 72-week treatment. The findings of this study suggest that in patients with fibrotic CHB receiving antiviral medication, the early phase reduction in LSM value was related to improved hepatic inflammation rather than fibrosis regression.

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.

New Insights on Using Oral Semaglutide versus Dapagliflozin in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Increases in both the prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity are closely related. Type 2 diabetes (T2DM) has been associated with metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis and hepatocellular carcinoma. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of T2DM and has an important role in weight loss. Also, it may represent a new therapeutic option for the treatment of MASH in obese diabetic patients. The main outcomes were changes from baseline in liver steatosis and fibrosis at week 24. A total of one hundred eighty-seven patients with T2DM were eligible for this prospective study; ninety-five subjects were treated with oral semaglutide, and ninety-two patients were treated with dapagliflozin as an add-on to metformin. All the subjects were evaluated using Vibration Controlled Transient Elastography (VCTE) from June to December 2022. From our cohort, 54% of the patients were females, with a mean age of 59.92 ± 11.89 years and a mean body mass index (BMI) of 29.53 ± 5.33 kg/m2. Following a six-month medication period, we observed a substantial reduction in anthropometric measurements, including the BMI, waist circumference (WC), and waist-to-hip ratio (WtHr), in both groups. Regarding HbA1c, a notable decrease was observed in the semaglutide group (p < 0.001) when compared to the dapagliflozin group (p = 0.011). In addition, the liver stiffness measurement (LSM) according to VCTE improved significantly in the semaglutide group participants from 8.07 ± 2.90 kPa at baseline to 6.51 ± 3.09 kPa after medication (p < 0.001). The superior metabolic effects of semaglutide, correlated to dapagliflozin, may contribute to a more efficient decrease in hepatic stress and injury, leading to a substantial enhancement of liver function in T2DM patients. Further investigations conducted over an ideal timeframe are necessary to confirm the evidence presented in this study.

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.

Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure.

Around 750,000 patients per year will be cured of HCV infection until 2030. Those with compensated advanced chronic liver disease remain at risk for hepatic decompensation and de novo HCC. Algorithms have been developed to stratify risk early after cure; however, data on long-term outcomes and the prognostic utility of these risk stratification algorithms at later time points are lacking. We retrospectively analyzed a cohort of 2335 patients with compensated advanced chronic liver disease (liver stiffness measurement≥10kPa) who achieved HCV-cure by interferon-free therapies from 15 European centers (median age 60.2±11.9y, 21.1% obesity, 21.2% diabetes).During a median follow-up of 6 years, first hepatic decompensation occurred in 84 patients (3.6%, incidence rate: 0.74%/y, cumulative incidence at 6y: 3.2%); 183 (7.8%) patients developed de novo HCC (incidence rate: 1.60%/y, cumulative incidence at 6y: 8.3%), with both risks being strictly linear over time.Baveno VII criteria to exclude (FU-liver stiffness measurement <12kPa and follow-up platelet count >150g/L) or rule-in (FU-liver stiffness measurement ≥25kPa) clinically significant portal hypertension (CSPH) stratified the risk of hepatic decompensation with proportional hazards. Estimated probability of CSPH discriminated patients developing versus not developing hepatic decompensation in the gray zone (ie, patients meeting none of the above criteria).Published HCC risk stratification algorithms identified high-incidence and low-incidence groups; however, the size of the latter group varied substantially (9.9%-69.1%). A granular "HCC-sustained virologic response" model was developed to inform an individual patient's HCC risk after HCV-cure. In patients with compensated advanced chronic liver disease, the risks of hepatic decompensation and HCC remain constant after HCV-cure, even in the long term (>3y). One-time post-treatment risk stratification based on noninvasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.

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.

Performance of novel collagen turnover biomarkers to detect increased liver stiffness in MASLD.

Cleavage products from collagen formation and degradation hold potential as first-line biomarkers for the risk of advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we evaluated the performance of PRO-C3, PRO-C6, C4M, PRO-C18L, and the clinical score ADAPT (age, diabetes, PRO-C3, and platelet count) to detect patients with an LSM >8kPa or >12kPa in comparison to the Fibrosis-4 Index (FIB-4). Serum from patients with MASLD (n=269) from six Swedish University Hospitals was analyzed using enzyme-linked immunosorbent assay-based methods. Liver stiffness measurement (LSM) by vibration-controlled transient elastography was performed. The area under the curve (AUC), calibration curves, and net benefit analysis were used. An LSM >8kPa was found in 108 (40.1%) patients. PRO-C3, PRO-C6, C4M, and PRO-C18L had AUCs ranging from 0.48 to 0.62. ADAPT had the highest AUC (0.73, 95% confidence interval [CI]=0.67-0.79) to detect patients >8kPa, compared to FIB-4 (0.71, (95%CI=0.64-0.77, p=0.35), and had a higher net benefit compared to FIB-4 from a probability threshold of 15%. FIB-4 and ADAPT performed equally well to detect patients with an LSM >12kPa, AUC 0.76 versus 0.76, p=0.93. ADAPT seems to be marginally better than FIB-4 in identifying patients with an LSM >8kPa. However, the clinical utility of ADAPT as a first line test is uncertain, especially in low-risk populations. The overall performance of FIB-4 was similar to that of ADAPT in detecting patients with an LSM of >12kPa. Altogether, the results suggest that ADAPT might be useful to detect earlier stages of fibrosis in MASLD, but that FIB-4 remains a first-line test for advanced fibrosis.

Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

BACKGROUND. Liver fibrosis is an important clinical endpoint of the progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. OBJECTIVE. The purpose of this study was to assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. METHODS. This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD (primary sclerosing cholangitis [PSC], autoimmune sclerosing cholangitis [ASC], or autoimmune hepatitis [AIH]). The registry was searched to identify patients who underwent both a research abdominal 1.5-T MRI examination that included liver MRE (performed for registry enrollment) and a clinically indicated liver biopsy within 6 months of that examination. MRE used a 2D gradient-recalled echo sequence. One analyst measured mean liver shear stiffness (in kilopascals) for each examination. Laboratory markers of liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] score) were recorded. For investigational purposes, one pathologist, blinded to clinical and MRI data, determined histologic Metavir liver fibrosis stage. The Spearman rank order correlation coefficient was calculated between MRE liver stiffness and Metavir liver fibrosis stage. ROC analysis was used to evaluate diagnostic performance for identifying advanced fibrosis (i.e., differentiating Metavir F0-F1 from F2-F4 fibrosis), and sensitivity and specificity were calculated using the Youden index. RESULTS. The study included 46 patients (median age, 16.6 years [IQR, 13.7-17.8 years]; 20 female patients, 26 male patients); 12 had PSC, 10 had ASC, and 24 had AIH. Median MRE liver stiffness was 2.9 kPa (IQR, 2.2-4.0 kPa). MRE liver stiffness and Metavir fibrosis stage showed strong positive correlation (ρ = 0.68). For identifying advanced liver fibrosis, MRE liver stiffness had an AUC of 0.81, with sensitivity of 65.4% and specificity of 90.0%; APRI had an AUC of 0.72, with sensitivity of 64.0% and specificity of 80.0%; and FIB-4 score had an AUC of 0.71, with sensitivity of 60.0% and specificity of 85.0%. CONCLUSION. MRE liver stiffness measurements were associated with histologic liver fibrosis severity. CLINICAL IMPACT. The findings support a role for MRE in noninvasive monitoring of liver stiffness, a surrogate for fibrosis, in children and young adults with AILD. TRIAL REGISTRATION. ClinicalTrials.gov NCT03175471.

A Comparative Study of Novel Fibrosis Index and Other Non-invasive Serum Indices for Predicting Fibrosis in Patients of Chronic Liver Disease.

Introduction Chronic liver diseaseprogression leads to liver fibrosis/cirrhosis. Transient Elastography is used for staging liver fibrosis but ascites, obesity, and operator experience limit its applicability. In this study, we compared various non-invasive serum indices in predicting fibrosis in chronic liver disease patients. Materials and methods A total of 142 cases of confirmed Chronic Liver Disease were included. Quantitative determination of liver stiffness by Transient Elastography and relevant blood investigations was done. We compared the liver stiffness measurement by Transient Elastography and fibrosis indices, i.e., Aspartate Transaminase (AST) to Alanine Transaminase (ALT) Ratio (AAR), AST to Platelet Ratio Index (APRI), Fibrosis Index (FI), Fibrosis-4 (FIB-4) Index, Age-Platelet Index (API), Pohl score, and Fibrosis Cirrhosis Index (FCI) with Novel Fibrosis Index (NFI), to predict liver fibrosis stages. Results The optimum cutoff of NFI for the F4 stage was ≥ 6670 with a sensitivity of 75.8% and specificity of 81.8%, for the F3 stage was ≥ 2112 with a sensitivity of 63.6%and specificity of 72.7%, and for the F2 stage was ≥ 1334 with a sensitivity of 100% and specificity of 56.3%. The NFI had the maximum area under the curve compared to other indices in predicting fibrosis stages. Conclusion The Novel Fibrosis Index was the best in predicting fibrosis stages in Chronic Liver Disease patients, with good performance in predicting the F4 stage.

Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis

Background & aimsIn primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. MethodsWe conducted an international retrospective cohort study among PBC patients treated with ursodeoxycholic acid (UDCA) and followed by vibration-controlled transient elastography (VCTE) between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation (LT) or death, was quantified using the hazard ratio (HR) and its confidence interval (CI). ResultsA total of 6,362 LSMs were performed in 3,078 patients (2,007 on UDCA alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1,000 person-years). LSM progressed in 59% of patients (mean 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (p<0.001). For example, the adjusted HRs (95% CI) associated with a 20% annual variation in LSM were 2.13 (1.89 – 2.45) for the increase and 0.40 (0.33 – 0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or LT was considered. ConclusionsTracking longitudinal changes in LSM using VCTE provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate endpoint in PBC clinical trials.

Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease.

Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver-related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD). This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB-4). ΔLSM was defined as [(follow-up LSM-baseline LSM)/baseline LSM×100]. We recorded LREs and all-cause mortality during a median follow-up time of 46months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression. Baseline FIB-4, baseline LSM, ΔFIB-4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00-1.07; 1.02, 95% CI, 1.01-1.03; 1.06, 95% CI, 1.03-1.09; 1.96, 95% CI, 1.63-2.35, 1.02, 95% CI, 1.01-1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time-dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n=390; reference), intermediate risk (n=446; HR=3.38), high risk (n=272; HR=5.64), and extremely high risk (n=164; HR=11.11). Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction.

Screening patients in general practice for advanced chronic liver disease using an innovative IT solution: The Liver Toolkit.

Identifying patients with undiagnosed advanced chronic liver disease (ACLD) is a public health challenge. Patients with advanced fibrosis or compensated cirrhosis have much better outcomes than those with decompensated disease and may be eligible for interventions to prevent disease progression. A cloud-based software solution ("the Liver Toolkit") was developed to access primary care practice software to identify patients at risk of ACLD. Clinical history and laboratory results were extracted to calculate aspartate aminotransferase-to-platelet ratio index and fibrosis 4 scores. Patients identified were recalled for assessment, including Liver Stiffness Measurement (LSM) via transient elastography. Those with an existing diagnosis of cirrhosis were excluded. Existing laboratory results of more than 32,000 adults across nine general practices were assessed to identify 703 patients at increased risk of ACLD (2.2% of the cohort). One hundred seventy-nine patients (26%) were successfully recalled, and 23/179 (13%) were identified to have ACLD (LSM ≥10.0kPa) (10% found at indeterminate risk [LSM 8.0-9.9kPa] and 77% low risk of fibrosis [LSM <8.0kPa]). In most cases, the diagnosis of liver disease was new, with the most common etiology being metabolic dysfunction-associated steatotic liver disease (n=20, 83%). Aspartate aminotransferase-to-platelet ratio index ≥1.0 and fibrosis 4 ≥3.25 had a positive predictive value for detecting ACLD of 19% and 24%, respectively. Patients who did not attend recall had markers of more severe disease with a higher median aspartate aminotransferase-to-platelet ratio index score (0.57 vs. 0.46, p=0.041). This novel information technology system successfully screened a large primary care cohort using existing laboratory results to identify patients at increased risk ACLD. More than 1 in 5 patients recalled were found to have liver disease requiring specialist follow-up.

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.

Deep learning for predicting fibrotic progression risk in diabetic individuals with metabolic dysfunction-associated steatotic liver disease initially free of hepatic fibrosis

ObjectiveMetabolic dysfunction-associated steatotic liver disease (MASLD) significantly impacts patients with type 2 diabetes mellitus (T2DM), where current non-invasive assessment methods show limited predictive power for future fibrotic progression. This study aims to develop an enhanced deep learning (DL) model that integrates ultrasound elastography images with clinical data, refining the prediction of fibrotic progression in T2DM patients with MASLD who initially exhibit no signs of hepatic fibrosis. MethodsWe enrolled 946 diabetic MASLD patients without advanced fibrosis, confirmed by initial liver stiffness measurements (LSM) below 6.5 kPa. Patients were divided into a training dataset of 671 and a testing dataset of 275. Hepatic shear wave elastography (SWE) images measured liver stiffness, classifying participants based on progression. A DL integrated model (DI-model) combining SWE images and clinical data was trained and its predictive performance compared with individual Image and Tabular models, as well as a logistic regression model on the testing dataset. ResultsFibrotic progression was observed in 18.1 % of patients over three years. During the training phase, the DI-model outperformed other models, achieving the lowest validation loss of 0.161 and highest accuracy of 0.933 through cross-validation. In the testing phase, it demonstrated robust discrimination with AUCs of 0.884 and 0.903 for the receiver operating characteristic and precision-recall curves, respectively, clearly outperforming other models. Shapley analysis identified BMI, LSM, and glycated hemoglobin as critical predictors. ConclusionThe DI-model significantly enhances the prediction of future fibrotic progression in diabetic MASLD patients, demonstrating the benefit of combining clinical and imaging data for early diagnosis and intervention.

Visceral Fat and Diabetes: Associations With Liver Fibrosis in Metabolic Dysfunction–Associated Steatotic Liver Disease

BackgroundThe prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is increasing globally. Noninvasive methods, such as bioelectrical impedance analysis (BIA), which measures body composition, including visceral fat, are gaining interest in evaluating MASLD patients. Our study aimed to identify factors associated with significant liver fibrosis, compare noninvasive scores, and highlight the importance of visceral fat measurement using BIA. MethodsMASLD patients seen in our OPD underwent comprehensive evaluations, including liver stiffness using transient elastography, body composition analysis using BIA, and metabolic measurements. Significant fibrosis was defined as liver stiffness measurement ≥8.2 kPa. Using multivariate analysis, we identified factors associated with significant liver fibrosis and compared four noninvasive scores with a novel DVF15 score. ResultsWe analyzed data from 609 MASLD patients seen between February 2022 and March 2023. The median age was 43 years (81% male). Among these, 78 (13%) had significant fibrosis. Patients with significant fibrosis had higher rates of type 2 diabetes (41% vs 21%, p<0.001) and elevated levels of AST, ALT, HbA1c, Fib-4, APRI, and NFS scores. They also exhibited higher visceral and subcutaneous fat. Binary logistic regression revealed type 2 diabetes and visceral fat >15% as associated with significant liver fibrosis. Additionally, the DVF15 score, combining these factors, showed a modest area under the ROC curve of 0.664 (p<0.001). ConclusionOur study identified diabetes and high visceral fat as factors associated with significant liver fibrosis in MASLD patients. We recommend that visceral fat measurement using BIA be an essential part of MASLD evaluation. The presence of either diabetes or visceral fat >15% should prompt clinicians to check for significant fibrosis in MASLD patients. Further research is warranted to validate our findings and evaluate the utility of the DVF15 score in larger cohorts and diverse populations.

Liver stiffness measurement by magnetic resonance elastography predicts cirrhosis and decompensation in alcohol-related liver disease

PurposeTo evaluate magnetic resonance elastography (MRE)—based liver stiffness measurement as a biomarker to predict the onset of cirrhosis in early-stage alcohol-related liver disease (ALD) patients, and the transition from compensated to decompensated cirrhosis in ALD.MethodsPatients with ALD and at least one MRE examination between 2007 and 2020 were included in this study. Patient demographics, liver chemistries, MELD score (within 30 days of the first MRE), and alcohol abstinence history were collected from the electronic medical records. Liver stiffness and fat fraction were measured. Disease progression was assessed in the records by noting cirrhosis onset in early-stage ALD patients and decompensation in those initially presenting with compensated cirrhosis. Nomograms and cut-off values of liver stiffness, derived from Cox proportional hazards models were created to predict the likelihood of advancing to cirrhosis or decompensation.ResultsA total of 182 patients (132 men, median age 57 years) were included in this study. Among 110 patients with early-stage ALD, 23 (20.9%) developed cirrhosis after a median follow-up of 6.2 years. Among 72 patients with compensated cirrhosis, 33 (45.8%) developed decompensation after a median follow-up of 4.2 years. MRE-based liver stiffness, whether considered independently or adjusted for age, alcohol abstinence, fat fraction, and sex, was a significant and independent predictor for both future cirrhosis (Hazard ratio [HR] = 2.0–2.2, p = 0.002–0.003) and hepatic decompensation (HR = 1.2–1.3, p = 0.0001–0.006). Simplified Cox models, thresholds, and corresponding nomograms were devised for practical use, excluding non-significant or biased variables.ConclusionsMRE-based liver stiffness assessment is a useful predictor for the development of cirrhosis or decompensation in patients with ALD.Graphical

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.

Non-Invasive Monitoring of the Impact of Low-Level Viremia on Liver Fibrosis in Treated Chronic Hepatitis B Patients.

Chronic hepatitis B (CHB) presents a global health challenge due to its potential to cause severe liver conditions such as hepatocellular carcinoma (HCC) and cirrhosis. Prior research has established a correlation between CHB infection with low-level viremia (LLV) and liver disease progression, such as increased HCC incidence. This study aims to investigate whether LLV during treatment with nucleos(t)ide analogs (NAs) contributes to the accelerated progression of liver fibrosis (LF). This retrospective cohort study at Jinhua Central Hospital focused on CHB patients undergone NA monotherapy for over 96 weeks. Patients were categorized into maintained virological response (MVR) and LLV groups based on hepatitis B virus (HBV) DNA levels. The study assessed LF using various markers and methods, including chitinase 3-like 1 protein (CHI3L1), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and transient elastography. Analysis was conducted on 92 CHB patients, categorized into LLV (n=42) and MVR (n=50) groups, following the exclusion of 101 patients for various reasons. Significant findings included lower baseline HBV DNA in MVR (<20 IU/mL) compared to LLV (67.8 IU/mL, P<0.001) and different AST/ALT ratios (LLV: 1.1, MVR: 1.36, P=0.011). LF was assessed using CHI3L1, FIB-4, and APRI, with LLV showing a higher baseline CHI3L1 (LLV:83.3 ng/mL vs MVR: 54.5 ng/mL, P=0.016) and scores compared to MVR, indicative of fibrosis. CHI3L1 levels in LLV were higher at baseline and weeks 48, 72, and 96 than MVR, with significance at baseline (P=0.038) and week 48 (P=0.034). Liver stiffness measurement (LSM) showed a time-dependent decline in both groups but no significant intergroup differences. Non-invasive monitoring of CHB patients who have received treatment indicates that LLV contributes to the progression of LF, necessitating proactive adjustment of antiviral treatment strategies.