OBJECTIVE: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE).
MAIN OUTCOMES AND MEASURES: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests.
RESULTS: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group.
CONCLUSIONS AND RELEVANCE: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.
METHODS: All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study. Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase (FAST), Agile 3+ and Agile 4 scores. Impaired renal function and chronic kidney disease (CKD) were defined by an estimated glomerular filtration rate (eGFR) with value of < 90 mL/min/1.73 m2 and < 60 mL/min/1.73 m2, respectively, as estimated by the CKD-Epidemiology Collaboration (CKD-EPI) equation.
RESULTS: Among 529 included NAFLD patients, the prevalence rates of impaired renal function and CKD were 37.4% and 4.9%, respectively. In multivariate analysis, a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+ and Agile 4 scores were independent risk factors for CKD (P< 0.05). Furthermore, increased fasting plasma glucose (FPG) and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome (P< 0.05). Compared with patients with normoglycemia, those with prediabetes [FPG ≥ 5.6 mmol/L or hemoglobin A1c (HbA1c) ≥ 5.7%] were more likely to have impaired renal function (P< 0.05).
CONCLUSIONS: Agile 3+ and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD. Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.
OBJECTIVES: To determine the prevalence and characteristics of NAFLD in individuals with metabolically healthy obesity.
SETTING: A tertiary, academic, referral hospital.
METHODS: All patients who underwent bariatric surgery with intraoperative liver biopsy from 2008 to 2015 were identified. Patients with preoperative hypertension, dyslipidemia, or prediabetes/diabetes were excluded to identify a cohort of metabolically healthy obesity patients. Liver biopsy reports were reviewed to determine the prevalence of NAFLD.
RESULTS: A total of 270 patients (7.0% of the total bariatric surgery patients) met the strict inclusion criteria for metabolically healthy obesity. The average age was 38 ± 10 years and the average body mass index was 47 ± 7 kg/m2. Abnormal alanine aminotransferase (>45 U/L) and asparate aminotransferase levels (>40 U/L) were observed in 28 (10.4%) and 18 (6.7%) patients, respectively. A total of 96 (35.5%) patients had NAFLD with NALFD Activity Scores 0 to 2 (n = 61), 3 to 4 (n = 25), and 5 to 8 (n = 10). A total of 62 (23%) patients had lobular inflammation, 23 (8.5%) had hepatocyte ballooning, 22 (8.2%) had steatohepatitis, and 12 (4.4%) had liver fibrosis.
CONCLUSION: Even with the use of strict criteria to eliminate all patients with any metabolic problems, a significant proportion of metabolically healthy patients had unsuspected NAFLD. The need and clinical utility of routine screening of obese patients for fatty liver disease and the role of bariatric surgery in the management of NAFLD warrants further investigation.
AIMS: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients.
METHODS: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria).
RESULTS: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set).
CONCLUSIONS: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients.
AIMS: We developed and validated MAFLD fibrosis score (MFS) for identifying advanced fibrosis (≥F3) among MAFLD patients.
METHODS: This cross-sectional, multicentre study consecutively recruited MAFLD patients receiving tertiary care (Malaysia as training cohort [n = 276] and Hong Kong and Wenzhou as validation cohort [n = 431]). Patients completed liver biopsy, vibration-controlled transient elastography (VCTE), and clinical and laboratory assessment within 1 week. We used machine learning to select 'highly important' predictors of advanced fibrosis, followed by backward stepwise regression to construct MFS formula.
RESULTS: MFS was composed of seven variables: age, body mass index, international normalised ratio, aspartate aminotransferase, gamma-glutamyl transpeptidase, platelet count, and history of type 2 diabetes. MFS demonstrated an area under the receiver-operating characteristic curve of 0.848 [95% CI 0.800-898] and 0.823 [0.760-0.886] in training and validation cohorts, significantly higher than aminotransferase-to-platelet ratio index (0.684 [0.603-0.765], 0.663 [0.588-0.738]), Fibrosis-4 index (0.793 [0.735-0.854], 0.737 [0.660-0.814]), and non-alcoholic fatty liver disease fibrosis score (0.785 [0.731-0.844], 0.750 [0.674-0.827]) (DeLong's test p
METHODS: This is a single-centre prospective study of a well-characterized cohort of MAFLD patients who underwent liver biopsy and followed every 6-12 months for adverse clinical outcomes.
RESULTS: The data for 202 patients were analyzed [median age 55.0 (48.0-61.3) years old; male, 47.5%; obese, 88.6%; diabetes mellitus, 71.3%; steatohepatitis, 76.7%; advanced fibrosis, 27.2%]. The median follow-up interval was 7 (4-8) years. The cumulative incidence of liver-related events, cardiovascular events, malignancy and mortality was 0.43, 2.03, 0.60 and 0.60 per 100 person-years of follow-up, respectively. Liver-related events were only seen in patient with advanced fibrosis at 9.1% vs 0% in patient without advanced liver fibrosis (p liver-related events among patients with advanced fibrosis was 1.67 per 100 person-years of follow-up. When further stratified to bridging fibrosis and cirrhosis, the cumulative incidence of liver-related events was 1.47 and 3.85 per 100 person-years of follow-up, respectively. Advanced fibrosis was not significantly associated with cardiovascular events, malignancy or mortality. The cumulative incidence of liver-related events, cardiovascular events, malignancy and mortality were not significantly different between patients with and without steatohepatitis and between obese and non-obese patients. However, liver-related events were only seen among obese patients.
CONCLUSION: Overall, the cumulative incidence of liver-related event is low in patients with MAFLD, but it is much higher among those with advanced fibrosis. However, there is a relatively high cumulative incidence of cardiovascular event among patients with MAFLD.
METHODS: In a cross-sectional study of 379 hemodialysis patients, FibroTouch transient elastography was performed on all patients. Erythropoeitin resistance index (ERI) was used to measure the responsiveness to ESA. Patients in the highest tertile of ERI were considered as having ESA hypo-responsiveness.
RESULTS: The percentage of patients with ESA hypo-responsiveness who had MAFLD was lower than patients without ESA hypo-responsiveness. FIB-4 index was significantly higher in ESA hypo-responsive patients. In multivariate analysis, female gender (aOR = 3.4, 95% CI = 1.9-6.2, p < 0.001), dialysis duration ≥50 months (aOR = 1.8, 95% CI = 1.1-2.9, p < 0.05), elevated waist circumference (aOR = 0.4, 95% CI = 0.2-0.8, p = 0.005), low platelet (aOR = 2.6, 95% CI 1.3-5.1, p < 0.01), elevated total cholesterol (aOR = 0.5, 95% CI 0.3-0.9, p < 0.05) and low serum iron (aOR = 3.8, 95% CI = 2.3-6.5, p < 0.001) were found to be independent factors associated with ESA hypo-responsiveness. Neither MAFLD nor advanced liver fibrosis was independently associated with ESA hypo-responsiveness. However, every 1 kPA increase in LSM increased the chance of ESA-hyporesponsiveness by 13% (aOR = 1.1, 95% CI = 1.0-1.2, p = 0.002) when UAP and LSM were used instead of presence of MAFLD and advanced liver fibrosis, respectively.
CONCLUSION: MAFLD and advanced liver fibrosis were not independently associated with ESA hypo-responsiveness. Nevertheless, higher FIB-4 score in ESA hypo-responsive group and significant association between LSM and ESA hypo-responsiveness suggest that liver fibrosis may be a potential clinical marker of ESA hypo-responsiveness.