Body posture can modulate liver stiffness measured by transient elastography: a prospective observational study.

BACKGROUND: Non-invasive measurement of liver stiffness (LS), traditionally performed in the supine position, has been established to assess liver fibrosis. However, fibrosis degree is not the sole determinant of LS, necessitating the identification of relevant confounders. One often-overlooked factor is body posture, and it remains unclear whether normal daily postures interfere with LS irrespective of fibrosis. A prospective two-group comparison study was conducted to investigate the relationship between posture and LS. METHODS: Sixty-two adults participated, divided into two groups: patients with chronic liver disease and healthy controls. Both groups were assessed using transient elastography (TE) under the supine, seated, and standing postures. Randomization was applied to the order of the two upright postures. A two-way mixed ANOVA was conducted to assess the posture-dependence of LS and its variations between two groups. RESULTS: Results showed that posture differentially affected LS depending on the presence of liver fibrosis. In 31 healthy individuals (baseline LS range: 3.5-6.8 kPa), a transition from the supine (5.0 ± 1.0 kPa) to seated (5.7 ± 1.4 kPa; p = 0.036) or standing (6.2 ± 1.7 kPa; p = 0.002) positions increased LS, indicating liver stiffening. Conversely, in 31 patients with varying fibrosis stages (baseline LS range: 8.8-38.2 kPa), posture decreased LS from the supine (15.9 ± 7.3 kPa) to seated (13.8 ± 6.2 kPa; p < 0.001) or standing (13.9 ± 6.2 kPa; p = 0.001) positions. No significant difference in LS was observed between the seated and standing positions in both groups (control group: 5.7 vs. 6.2 kPa, p = 0.305; patient group: 13.8 vs. 13.9 kPa, p = 1). Additionally, different postures did not elicit significant changes in the success rate (supine, 98.6 ± 4%; seated, 97.6 ± 6%; standing, 99.1 ± 3%; p = 0.258) and IQR/median value (supine, 25 ± 8%; seated, 29 ± 15%; standing, 29 ± 12%; p = 0.117), implying no impact on both measurement feasibility and reliability. CONCLUSIONS: We demonstrated, for the first time, the feasibility of utilizing upright postures as an alternative measurement protocol for TE. We further unravel a previously unrecognized role of transitioning between different postures to assist the diagnosis of cirrhosis. The findings suggested that daily physiological activity of postural changes suffices to alter LS. Therefore, body positioning should be standardized and carefully considered when interpreting LS.

Meta-analysis: accuracy of the Baveno VI criteria for the diagnosis of high-risk varices in patients with hepatocellular carcinoma.

Background and aim: Diagnosing high-risk varices (HRV) is crucial for determining the prognosis and treatment strategy in patients with hepatocellular carcinoma (HCC). Although the Baveno VI consensus guidelines have been validated for assessing HRV in patients with liver cirrhosis, their applicability to those with HCC remains uncertain. This study aims to evaluate the effectiveness of the Baveno VI criteria in screening for HRV in patients with HCC. Methods: We searched for English-language articles related to Baveno criteria and HCC across PubMed, Embase, Web of Science, and Cochrane databases, covering publications from their inception until April 19, 2024. Our meta-analysis was conducted using STATA 14.0 and Meta-Disc 1.4 software. We assessed the quality of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We analyzed pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) using a random-effects model and constructed a summary receiver operating characteristic (SROC) curve. Based on established consensus, the favorable Baveno VI criteria were defined as a liver stiffness measurement (LSM) < 20 kPa and a platelet count (PLT) > 150×109/L to exclude HRV. This study is registered with PROSPERO under the registration number CRD42024533946. Results: We finally brought four studies, including 1277 patients with HCC, into this meta-analysis. The SEN, SPE, DOR, and AUC of favorable Baveno VI criteria in screening HRV in patients with HCC were 0.90 (95% CI: 0.81-0.95), 0.33 (95% CI: 0.25-0.41), 4.44 (95% CI: 2.14-9.22), and 0.59 (95% CI: 0.55-0.64), respectively. The LR+ and LR- of the favorable Baveno VI criteria were 1.34 (95% CI: 1.19-1.50) and 0.30 (95% CI: 0.16-0.58), respectively. Subgroup and meta-regression analyses indicated that BCLC and Child-Pugh stages likely contribute to the heterogeneity in the SPE. Conclusions: The favorable Baveno VI criteria may not effectively screen HRV in patients with HCC. However, the current evidence is insufficient, and further studies with larger sample sizes and detailed patient subgroups are needed. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024533946.

Diagnostic and prognostic performance of the LiverRisk score in tertiary care.

Background & Aims: The LiverRisk score has been proposed as a blood-based tool to estimate liver stiffness measurement (LSM), thereby stratifying the risk of compensated advanced chronic liver disease (cACLD, LSM ≥10 kPa) and liver-related events in patients without known chronic liver disease (CLD). We aimed to evaluate its diagnostic/prognostic performance in tertiary care. Methods: Patients referred to two hepatology outpatient clinics (cohort I, n = 5,897; cohort II, n = 1,558) were retrospectively included. Calibration/agreement of the LiverRisk score with LSM was assessed, and diagnostic accuracy for cACLD was compared with that of fibrosis-4 (FIB-4)/aspartate aminotransferase-to-platelet ratio index (APRI). The prediction of hepatic decompensation and utility of proposed cut-offs were evaluated. Results: In cohort I/II, mean age was 48.3/51.8 years, 44.2%/44.7% were female, predominant etiologies were viral hepatitis (51.8%)/metabolic dysfunction-associated steatotic liver disease (63.7%), median LSM was 6.9 (IQR 5.1-10.9)/5.8 (IQR 4.5-8.8) kPa, and 1,690 (28.7%)/322 (20.7%) patients had cACLD.Despite a moderate correlation (Pearson's r = 0.325/0.422), the LiverRisk score systematically underestimated LSM (2.93/1.80 points/kPa lower), and range of agreement was wide, especially at higher values.The diagnostic accuracy of the LiverRisk score for cACLD (area under the receiver operator characteristics curve [AUROC] 0.757/0.790) was comparable to that of FIB-4 (AUROC 0.769/0.813) and APRI (AUROC 0.747/0.765). The proposed cut-off of 10 points yielded an accuracy of 74.2%/81.2%, high specificity (91.9%/93.4%), but low negative predictive value (76.6%/84.5%, Cohen's κ = 0.260/0.327).In cohort I, 208 (3.5%) patients developed hepatic decompensation (median follow-up 4.7 years). The LiverRisk score showed a reasonable accuracy for predicting hepatic decompensation within 1-5 years (AUROC 0.778-0.832). However, it was inferior to LSM (AUROC 0.847-0.901, p <0.001) and FIB-4 (AUROC 0.898-0.913, p <0.001). Similar to the strata of other non-invasive tests, the proposed LiverRisk groups had distinct risks of hepatic decompensation. Conclusions: The LiverRisk score did not improve the diagnosis of cACLD or prediction of hepatic decompensation in the tertiary care setting. Impact and implications: The LiverRisk score has been proposed as a non-invasive tool to estimate liver stiffness measurement and thus the risk of compensated advanced chronic liver disease and liver-related events. As automatic implementation into lab reports is being discussed, the question of its applicability outside of opportunistic screening in the general population arises. In two large cohorts of patients referred to hepatology outpatient clinics, the LiverRisk score did not accurately predict liver stiffness, did not improve cACLD identification, and had a lower predictive performance for hepatic decompensation as compared with FIB-4. Although it represents a major step forward for screening patients without known liver disease in primary care, our findings indicate that the LiverRisk score does not improve patient management outside the primary care setting, that is, in cohorts with a higher pre-test probability of cACLD.

A Prediction Nomogram of Severe Obstructive Sleep Apnea in Patients with Obesity Based on the Liver Stiffness and Abdominal Visceral Adipose Tissue Quantification.

Purpose: The diagnosis of severe OSA still relies on polysomnography, which causes a strong sense of restraint in patients with obesity. However, better prediction tools for severe OSA applicable to patients with obesity have not been developed. Patients and Methods: Relevant clinical data of 1008 patients with OSA who underwent bariatric surgery in our hospital were collected retrospectively. Patients were divided into training and test cohorts by machine learning. Univariate and multivariate logistic regression analysis was used to screen associations, including liver stiff measurement (LSM) and abdominal visceral tissue (aVAT), and to construct a severe OSA risk prediction nomogram. Then, we evaluated the effectiveness of our model and compared our model with the traditional Epworth Sleepiness Scale (ESS) model. Finally, our associations were used to explore the correlation with other indicators of OSA severity. Results: Our study revealed that age, biological sex, BMI, LSM, aVAT, and LDL were independent risk factors for severe OSA in patients with obesity. A severe OSA risk prediction nomogram constructed by six indicators possessed high AUC (0.845), accuracy (77.6%), and relatively balanced specificity and sensitivity (72.4%, 82.8%). The Hosmer-Lemeshow test (P=0.296, 0.785), calibration curves, and DCA of the training and test cohorts suggested better calibration and more net clinical benefit. Compared with the traditional ESS model, our model had higher AUC (0.829 vs 0.545), sensitivity (78.9% vs 12.2%), PPV (77.9% vs 53.3%), and accuracy (75.4% vs 55.2%). In addition, the associations in our model were independently correlated with other indicators reflecting OSA severity. Conclusion: We provided a simple, cheap, and non-invasive nomogram of severe OSA risk prediction for patients with obesity, which would be helpful for preventing further complications associated with severe OSA.

Question: Can we predict severe OSA in patients with obesity by their metabolic complications through some non-invasive examinations? Findings: Compared with traditional questionnaires, we developed and validated a new prediction model, including liver stiffness measurement and abdominal visceral adipose tissue, to screen severe OSA in bariatric surgery candidates through non-invasive examinations, which may contribute to perioperative safety and ultimate weight loss outcomes. Meaning: For patients with obesity who are in hospital because of metabolic disorders, it is necessary for them to be screened for possible severe OSA according to our new prediction nomogram, which is helpful for preventing further complications and perioperative risk associated with severe OSA.

Prognostic Accuracy of Transient Elastography-Based Predictors in Diabetes and Obesity: A Multicenter International Cohort Study.

BACKGROUND/AIMS: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is recommended for risk stratification of patients with nonalcoholic fatty liver disease (NAFLD). More recently, AGILE3 + and AGILE4 have combined LSM with clinical parameters to identify patients with advanced fibrosis and cirrhosis, respectively. However, there are limited data on prognostic performance of these scores in key at-risk subgroups such as those with diabetes and obesity compared to LSM alone. METHODS: This is a retrospective cohort study including 1903 adult patients with NAFLD from tertiary care centers in the United States and Singapore undergoing VCTE between 2015 and 2022. Primary predictors were FAST, LSM, AGILE3 + , and AGILE4 scores and the primary outcome was liver-related events (LRE). Patients were further stratified by diabetes and obesity status. Prognostic performance was measured using the time-dependent area under the receiver operating characteristic curve (tAUC) at 5 years. RESULTS: In total, 25 LRE occurred and the overall incidence rate of LRE was 4.4 per 1000 person-years. tAUC for predicting LRE in the overall group was significantly higher with AGILE3 + (0.94 [95% CI: 0.90-0.98]) and AGILE4 (0.94 [95% CI: 0.90-0.98]) compared to LSM (0.87 [95% CI: 0.80-0.94]) (p = 0.001 and 0.009, respectively) and FAST (0.73 [95% CI: 0.59-0.86]) (p < 0.001 for both). Similarly, tAUC was significantly higher in those with T2D for AGILE3 + compared to LSM (0.92 vs 0.86, respectively) (p = 0.015) and FAST (0.92 vs 0.73, respectively) (p = 0.008). Among people with obesity, tAUC was significantly higher for AGILE3 + compared to LSM (0.95 vs 0.89, respectively) (p = 0.005) and FAST (0.95 vs 0.76, respectively) (p = 0.0035). Though AGILE4 had a higher tAUC in these subgroups compared to LSM, it did not reach statistical significance. CONCLUSION: AGILE3 + significantly outperforms LSM and FAST for predicting LRE in patients with NAFLD including in those with diabetes or obesity.

Multiparametric liver assessment in patients successfully treated for hepatitis C: a 4-year follow-up.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic liver disease, in which liver stiffness increases. Liver stiffness measurements (LSM) are therefore essential in diagnosing liver diseases and predicting disease development. The study objective was to perform a comprehensive prospective assessment of the liver before, after and 4 years after treatment for HCV, including an assessment of the long-term outcome of fibrosis, steatosis and inflammation. METHODS AND FINDINGS: Patients eligible for HCV treatment were included prospectively in 2018 (n = 47). Liver stiffness was measured using transient elastography and 2D shear-wave elastography (SWE). Blood tests, B-mode ultrasound (US) and SWE, were performed before, after (end of treatment [EOT]), 3 months after (EOT3) and 4 years after treatment (4Y). At the final visit, we added attenuation imaging and shear-wave dispersion slope (SWDS) measurements to assess steatosis and inflammation. Three months after treatment, the sustained virologic response rate was 93%. The median liver stiffness for baseline, EOT, EOT3 and 4Y was 8.1, 5.9, 5.6 and 6.3 kPa, respectively. There was a significant reduction in liver stiffness from baseline to EOT, and from EOT to EOT3. After 4 years, the mean attenuation coefficient (AC) was 0.58 dB/cm/MHz, and the mean SWDS value was 14.3 (m/s)/kHz. CONCLUSION: The treatment for HCV was highly effective. Measurements of liver stiffness decreased significantly after treatment and remained low after 4 years. AC measurements indicated low levels of liver steatosis. Shear-wave dispersion values indicated inflammation of the liver, but the clinical implication is undetermined and should be explored in larger studies.Clinicaltrials.gov: NCT03434470. ABBREVIATIONS: AC: attenuation coefficient; APRI: aspartate aminotransferase to platelet ratio index; ATI: attenuation imaging; cACLD: compensated advanced chronic liver disease; CAP: controlled attenuation parameter; FIB-4: Fibrosis-4 Index for liver fibrosis; HCC: hepatocellular carcinoma; LSM: liver stiffness measurement; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; SWDS: shear-wave dispersion slope; SWE: shear-wave elastography; US: ultrasound.

Evaluation of liver parenchyma with shear wave elastography in patients with rheumatoid arthritis receiving disease-modifying antirheumatic drug therapy.

BACKGROUND: Methotrexate (MTX) and leflunomide (LEF) play fundamental roles in rheumatoid arthritis (RA) treatment and require proper monitoring of side effects. Concerns about MTX/LEF-related liver fibrosis (LF) in patients with RA remain unclear. This study investigated liver stiffness using two-dimensional shear wave elastography (2D-SWE) in RA patients undergoing disease-modifying antirheumatic drug (DMARD) therapy. Moreover, 2D-SWE was employed to evaluate the correlations between liver stiffness, cumulative MTX and LEF doses and risk factors for substantial LF. METHODS: We recruited 222 participants from the Department of Rheumatology. The participants were divided into healthy controls (n = 78) and patients with RA (n = 144). Pearson's correlation analysis was performed to assess the correlations between liver stiffness and the cumulative dose of MTX/LEF and other clinical and laboratory variables. RESULTS: The mean elasticity modulus was 4.79 ± 0.92 kPa, excluding the presence of significant fibrosis. Mean 2D-SWE values were significantly lower in healthy controls than in RA treated with MTX and LEF. The cut-off ≥3.8 kPa 2D-SWE values with the sensitivity of 86.1%, specifity of 83.3%. 2D-SWE values were not significantly different across the strata of the cumulative MTX subgroups. CONCLUSIONS: MTX and LEF increase liver stiffness but may be considered low risk for the development of LF.

Dynamic Changes in ELF Score Predict Hepatocellular Carcinoma in Chronic Hepatitis B Patients Receiving Antiviral Treatment.

Enhanced liver fibrosis (ELF) score is a noninvasive assessment for liver fibrosis. We aimed to evaluate the performance of changes in ELF score 3 years apart in combination with liver stiffness measurement (LSM)-hepatocellular carcinoma (HCC) score to predict HCC in chronic hepatitis B (CHB) patients. This is a prospective cohort study. Patients who underwent transient elastography (TE) examinations and at intermediate or high risk of HCC defined by LSM-HCC score were invited to repeat the examination about 3 years later. Their serum samples at these two time points were retrieved to assess the ELF score changes. The primary endpoint was HCC. There were 445 CHB patients (males: 73.9%; mean age: 51.6 ± 10.3 years) who received two TE examinations and ELF scores. Among them, 252 (56.6%) and 193 (43.4%) patients were at intermediate and high HCC risk at first assessment defined by LSM-HCC score, respectively. Kaplan-Meier analysis showed that the changes in ELF score could stratify the HCC risk in both intermediate- and high-risk patients defined by LSM-HCC score (p < 0.001 for intermediate-risk group; p = 0.011 for high-risk group). Patients remained having mild or moderate fibrosis at both assessments had the lowest risk of HCC (4.0%), followed by patients with fibrosis regressed (11.3%; p = 0.014) during a mean follow-up of 163 months. Patients remained having or progressed to severe fibrosis were at highest risk of HCC (>20%). Consistent findings were demonstrated in patients at both intermediate and high risk of HCC defined by LSM-HCC score. Dynamic changes in ELF score provided additional value to LSM-HCC score for stratifying HCC risk in CHB patients.

Alpha-1 antitrypsin deficiency and Pi*Z allele as important co-factors in the development of liver fibrosis.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease, and Pi*Z allele is the most clinically relevant mutation. AIM: To evaluate the impact of clinical parameters and AATD phenotypes, particularly the Pi*Z allele, in liver fibrosis. METHODS: Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation. RESULTS: Included 69 patients, 49.3% had Pi*MZ phenotype and 10.1% Pi*ZZ. An age ≥ 55 years, age at diagnosis ≥ 41 years and AAT at diagnosis < 77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score (NFS) not excluding advanced fibrosis [area under the curve (AUC) = 0.840, P < 0.001; AUC = 0.836, P < 0.001; AUC = 0.681, P = 0.025]. An age ≥ 50 years and age at diagnosis ≥ 41 years predicted a fibrosis-4 index of moderate to advanced fibrosis (AUC = 0.831, P < 0.001; AUC = 0.795, P < 0.001). Patients with hypertension, type 2 diabetes mellitus (DM), dyslipidaemia, metabolic syndrome, and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis (P < 0.001, P = 0.002, P = 0.008, P < 0.001, P = 0.033). Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement ≥ 7.1 kPa (P = 0.040). CONCLUSION: Risk factors for liver disease in AATD included an age ≥ 50 years, age at diagnosis ≥ 41 years, metabolic risk factors, regular alcohol consumption, at least one Pi*Z allele, and AAT value at diagnosis < 77 mg/dL. We created an algorithm for liver disease screening in AATD patients to use in primary care, selecting those to be referred to Hepatology consultation.

Splenic Stiffness Measurement Combined With Liver Stiffness Measurement Compared With Baveno VII Criteria in Predicting the Presence of Oesophageal and Gastric Varices in Patients With Compensated Advanced Liver Cell Disease (cALCD).

INTRODUCTION: Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) is being increasingly used as a screening tool to predict varices. Our aim was to test the utility of Baveno VII criteria and other combinations of LSM, platelet count (PC), and splenic stiffness measurement (SSM) to predict the presence of varices in a cohort of Sri Lankan patients with compensated advanced liver cell disease (cALCD). METHODS: Consecutive patients with newly diagnosed Child-Pugh class A cALCD (non-viral, BMI<30) were recruited prospectively. They underwent gastroscopy. LSM and SSM were taken using vibration-controlled transient elastography (VCTE) (Echosens FibroScan 502 Touch; Echosens SA, Paris, France) by a single operator who was unaware of endoscopy findings. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of different Baveno VII criteria to predict the varices and different combinations of LSM, SSM, and PC were also explored. RESULTS: One hundred and seventy-four individuals were recruited. The mean age was 61.4 ((95% CI: 59.7-62.8) years. A total of 110 individuals were males, and 106 had varices. Our results indicated that the three Baveno VII criteria had sensitivities of 61%, 63%, and 42%, and specificities of 79%, 77%, and 87% to predict varices. SSM>30kPa alone and in combination with LSM>15kPa had sensitivities of 81 and 75%, specificities of 72 and 83%, PPVs of 82 and 87%, NPVs of 71% and 67%, and accuracies of 78 and 78%, respectively, to predict varices. CONCLUSION: Baveno VII criteria had a low sensitivity but high specificity in predicting the presence of varices. However, SSM>30kPa alone or in combination with LSM>15kPa had better sensitivity, specificity, PPV, NPV, and accuracy in predicting varices.

Effect of Indo-Mediterranean diet versus calorie-restricted diet in children with non-alcoholic fatty liver disease: A pilot randomized control trial.

BACKGROUND: Dietary interventions and increased physical activity are the cornerstones for management of the paediatric non-alcoholic fatty liver disease (NAFLD). Though, no specific diet has been proven superior, Indo-Mediterranean diet (IMD) has shown promise in adult literature. Thus, we aimed to compare the effect of IMD and a standard calorie-restricted diet (CRD) in Indian overweight children and adolescents with biopsy-proven NAFLD. METHODS: Thirty-nine consecutive biopsy-proven NAFLD children between the ages of 8 and 18 years were randomized into either IMD or CRD for 180 days, and various parameters were evaluated at baseline and then after 180 days (NCT05073588). RESULTS: A total of 34 subjects (18 in IMD and 16 in CRD group) completed the study. There was a significantly higher decrease in controlled attenuation parameter (CAP) values (as a marker of hepatic steatosis; on transient elastography) (95% CI: 4.2-73.4, p = 0.042), weight (95% CI: 0.75-5.5, p = 0.046) and body mass index (BMI) (95% CI: 0.21-2.05, p = 0.014) (but not in Pediatric NAFLD Fibrosis Index or PNFI; as a marker of hepatic fibrosis) in IMD group compared to the CRD group. Liver stiffness measurement, serum cholesterol and low-density lipoprotein levels and HOMA-IR decreased only in the IMD group (p < 0.001). Our statistical model showed that delta-Weight was the only independent variable associated with delta-CAP. CONCLUSION: Both IMD and CRD can improve the various anthropometric, clinical, imaging and biochemical parameters but IMD was superior to CRD in terms of reducing CAP values and weight/BMI over 180 days in overweight/obese NAFLD children.

Prevalence, clinical significance and prognosis value of liver stiffness measurement anomalies in transthyretin cardiac amyloidosis.

Background - Laboratory liver anomalies are common in cardiac amyloidosis; however, their significance regarding liver stiffness is unknown. The aim of this study was to investigate the prevalence, clinical significance, and prognostic value of liver stiffness measurement (LSM) anomalies in transthyretin cardiac amyloidosis (ATTR-CA). Methods - Consecutive patients diagnosed with ATTR-CA who underwent liver stiffness assessment were included in the study. Demographic, clinical, laboratory, transthoracic echocardiography and liver stiffness data were retrospectively collected. LSM was obtained through either transient elastography or supersonic shear imaging. Patient cohort was divided in two groups according to a 10 kPa threshold. Follow up data were collected for the occurrence of hospitalization for heart failure and all-cause death. Results - Two hundred and eighty-four patients with ATTR-CA - 26 (9 %) hereditary variant ATTR, 258 (91 %) wild-type ATTR - were included. A LSM over 10 kPa was found in 4 (15 %) and 98 (38 %) patients with ATTRv and ATTRwt respectively (p = 0.02). Among patients with ATTRwt, high LSM was more frequent in advanced stages of ATTR-CA and was associated with increased risk of hospitalization for heart failure after multivariate analysis with a hazard ratio of 2.41 [1.05-5.55] (p = 0.04). Among patients with NYHA stage 1, 28 % presented high LSM associated with high NT-proBNP levels. Integration of high LSM with NT-proBNP and estimated glomerular filtration rate provided a better estimate of patient survival. Conclusion - LSM over 10 kPa is found in up to 36 % of patients with ATTR-CA and is associated with advanced stages of cardiomyopathy and increased risk of hospitalization for heart failure in ATTRwt patients.

A Real-World Experience Utilizing the FAST Score to Identify Patients With Nonalcoholic Steatohepatitis Fibrosis.

Background and Aims: We aimed to test the performance of the Fibroscan-aspartate aminotransferase (FAST) score, a noninvasive test, to identify nonalcoholic steatohepatitis (NASH) and significant fibrosis (NASH + ≥F2) in a cohort of patients with a histological diagnosis of NASH, using a cutoff of ≥0.35 as a rule in factor. We also compared performance to liver stiffness measurement (LSM) ≥8 kPa and the fibrosis-4 index (FIB-4) ≥1.3 and attempted to identify risk factors to develop a model for improving diagnostic accuracy. Methods: Patients with histologically confirmed NASH were identified from 2020-2021. Demographic information, laboratory data, and LSM were collected. The FAST score and FIB-4 were calculated. Univariate and backward entry multivariate logistic regression analyses were performed to identify risk factors in addition to the FAST score ≥0.35 that are associated with an accurate histological diagnosis of NASH + ≥F2. Discrimination and overall accuracy were assessed using area under receiver operating characteristic curves. Results: Using a rule in cutoff of ≥0.35, the FAST score performed with a sensitivity, specificity, negative predictive value, and positive predictive value of 96.4%, 36.8%, 77.7%, and 81.8%, respectively. Age (P = .05) and FAST ≥0.35 (P = .001) correctly identified histologically confirmed NASH + ≥F2. The FAST + age model outperformed FAST ≥0.35 (0.70, confidence interval [CI]: 0.55-0.84), LSM ≥8 kPa (0.72, CI: 0.59-0.85), and FIB-4 ≥1.3 (0.73, CI: 0.59-0.87) with a c-statistic of 0.78 (CI: 0.64-0.92). Conclusion: A FAST score with a rule cutoff of ≥0.35 performed well (c-statistic: 0.70) and was superior to LSM and FIB-4 when age was incorporated into the model (0.78) in detecting NASH + ≥F2 fibrosis in the real world.

Fully automated hybrid approach on conventional MRI for triaging clinically significant liver fibrosis: A multi-center cohort study.

Establishing reliable noninvasive tools to precisely diagnose clinically significant liver fibrosis (SF, ≥F2) remains an unmet need. We aimed to build a combined radiomics-clinic (CoRC) model for triaging SF and explore the additive value of the CoRC model to transient elastography-based liver stiffness measurement (FibroScan, TE-LSM). This retrospective study recruited 595 patients with biopsy-proven liver fibrosis at two centers between January 2015 and December 2021. At Center 1, the patients before December 2018 were randomly split into training (276) and internal test (118) sets, the remaining were time-independent as a temporal test set (96). Another data set (105) from Center 2 was collected for external testing. Radiomics scores were built with selected features from Deep learning-based (ResUNet) automated whole liver segmentations on MRI (T2FS and delayed enhanced-T1WI). The CoRC model incorporated radiomics scores and relevant clinical variables with logistic regression, comparing routine approaches. Diagnostic performance was evaluated by the area under the receiver operating characteristic curve (AUC). The additive value of the CoRC model to TE-LSM was investigated, considering necroinflammation. The CoRC model achieved AUCs of 0.79 (0.70, 0.86), 0.82 (0.73, 0.89), and 0.81 (0.72-0.91), outperformed FIB-4, APRI (all p < 0.05) in the internal, temporal, and external test sets and maintained the discriminatory power in G0-1 subgroups (AUCs range, 0.85-0.86; all p < 0.05). The AUCs of joint CoRC-LSM model were 0.86 (0.79-0.94), and 0.81 (0.72-0.90) in the internal and temporal sets (p = 0.01). The CoRC model was useful for triaging SF, and may add value to TE-LSM.

Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis.

BACKGROUNDS/AIMS: Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using VCTE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. METHODS: A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used VCTE were finally registered. Hazard ratios (HRs) and the 95% confidence intervals (CIs) were considered summary estimates of treatment effect sizes of ≥11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model. RESULTS: Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45-4.54) in CHB patients with a baseline LSM of ≥11 kPa compared to patients who did not. In ten studies included, LSM of ≥11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50-71%) and 78% (95% CI, 66-86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70-0.77). CONCLUSION: The risk of HCC development was elevated in CHB patients with VCTE-determined LSM of ≥11 kPa. This finding suggests that VCTE-determined LSM values may aid the risk prediction of HCC development in CHB patients.

Role of splenic hepatic elastography ratio in differentiating non-cirrhotic portal fibrosis and chronic liver disease in children and adolescents.

BACKGROUND: Differentiation of Non-cirrhotic Portal Fibrosis (NCPF) from chronic liver disease (CLD) in children and adolescents with portal hypertension (PHT) is challenging especially in cases where liver stiffness measurement (LSM) and hepatic venous pressure gradient are higher. This objective of the current study was to evaluate the diagnostic accuracy of the splenic stiffness measurement (SSM)/LSM ratio in the diagnosis of NCPF. METHODS: From January 2019 to December 2023, consecutive children and adolescents of 6 months to 18 years of age with PHT (CLD and NCPF) were prospectively enrolled. Transient elastography (TE) for SSM and LSM, upper gastrointestinal endoscopy (UGIE), liver biopsy/trans-jugular liver biopsy, abdominal imaging, and laboratory evaluation were done. The relationship of TE parameters for diagnosis of NCPF and CLD was evaluated. Receiver-operating characteristic (ROC) statistics were applied using R Studio-4.2.2 statistical software. RESULTS: One hundred and forty seven with CLD and 27 patients with NCPF were evaluated. Median age was 10.0 (IQR 2.4-14.0) years; 68.4% were males. The AUROC of SSM/LSM ratio was better (0.992, 95%CI 0.982-1.0001) than LSM (0.945, 95%CI0.913-0.977) and SSM (0.626, 95%CI0.258-0.489) for the diagnosis of NCPF. SSM/LSM ratio cut-off of 3.67 predicted NCPF with an excellent sensitivity (100%), specificity (95.9%), and diagnostic accuracy (95.91%). The AUROC of SSM/LSM ratio was excellent and outperformed other TE parameters in the subgroups, i.e., LSM between 10 and 20 kPa (0.982, 95%CI 0.947-1.000), without clinically significant varices (CSV) (1.000, 95%CI 1.000-1.000) and with CSV (0.993, 95%CI 0.983-1.000). Diagnostic performance of SSM/LSM Ratio was better than LSM for discriminating NCPF from CLD using McNemar test (p = 0.01). CONCLUSION: The SSM/LSM ratio is an excellent tool in differentiating NCPF from CLD.

Elastography-The New Standard in the Assessment of Fibrosis After Pediatric Liver Transplantation?

BACKGROUND: The development of graft fibrosis after pediatric liver transplantation (PLT) remains a major concern as it can lead to graft failure and ultimately graft loss. Elastography is a non-invasive method to assess liver fibrosis, but its role in the posttransplant setting is unclear. The aim of our study was to evaluate shear wave elastography (SWE) in the assessment of liver fibrosis after PLT, including split-liver recipients. METHODS: We retrospectively analyzed data from PLT recipients who underwent surveillance liver biopsy and concurrent 2D-SWE during the study period from April 2018 to July 2021. Spearman's correlation was used to compare histologic fibrosis stages with liver stiffness measurements (LSM) by 2D-SWE. AUROC analysis was performed to evaluate the performance. One sample t-test was used to compare results with reference values of healthy children. RESULTS: 62 cases were included. 29% showed histologic fibrosis. LSM by 2D-SWE were feasible in all children regardless of age or graft type. There was a significant correlation between LSM and fibrosis stage for all three scoring systems used (Ishak, p = 0.003; METAVIR, p = 0.005; LAF Score, p = 0.003). Patients with a history of biliary complications had increased liver stiffness (p = 0.015). The AUROC of 2D-SWE for predicting significant liver graft fibrosis was 0.81. Liver stiffness after PLT without graft fibrosis was higher than in healthy subjects, but comparable to that in children with chronic liver disease without fibrosis. CONCLUSION: 2D-SWE can reliably detect children with significant liver graft fibrosis, even in split-liver recipients. This study demonstrates the value of a non-invasive tool for fibrosis staging after PLT. 2D-SWE has the potential to improve long-term outcomes after PLT and to reduce the number of surveillance liver biopsies. But elastography is not a substitute for liver biopsy.

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

Objective: Metabolic 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. Methods: We 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. Results: Fibrotic 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. Conclusion: The 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.

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

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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). 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.

Validation of Baveno VII criteria for clinically significant portal hypertension by two-dimensional shear wave elastography.

BACKGROUND: The Baveno VII consensus proposed criteria for the non-invasively diagnosis of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). The performance of Baveno VII criteria for assessing CSPH by two-dimensional shear wave elastography (2D-SWE) had not been well validated. We aimed to validate the performance of Baveno VII criteria for rule-in and rule-out CSPH by 2D-SWE. METHOD: This is an international multicenter study including cACLD patients from China and Croatia with paired liver stiffness measurement (LSM), spleen stiffness measurement (SSM) by 2D-SWE, and hepatic venous pressure gradient (HVPG) were included. CSPH was defined as HVPG ≥ 10 mmHg. RESULT: A total of 146 patients with cACLD were enrolled, and finally 118 patients were included in the analysis. Among them, CSPH was documented in 79 (66.9%) patients. Applying the Baveno VII criteria for rule-out CSPH by 2D-SWE, [LSM ≤ 15 kPa and platelet count ≥ 150 × 109/L] OR SSM < 21 kPa, could exclude CSPH with sensitivity > 90% (93.5 or 98.7%) but negative predictive value < 90% (74.1 or 85.7%). Using the Baveno VII criteria for rule-in CSPH by 2D-SWE, LSM ≥ 25 kPa OR SSM ≥ 50 kPa, could diagnose CSPH with 100% specificity and 100% positive predictive values. CONCLUSION: Baveno VII criteria by 2D-SWE showed a good diagnostic performance for ruling in but not for ruling out CSPH, which might become an emerging non-invasive elastography tool to select the patients who needed non-selective beta blocker therapy.