medwireNews: Vibration-controlled transient elastography (VCTE)-based Agile scores show high accuracy in predicting liver-related events (LREs) in patients with metabolic dysfunction–associated steatotic liver disease (MASLD), performing better than other commonly used noninvasive tests, indicate findings from a study published in JAMA.
The researchers calculated the Agile scores for over 16,000 individuals based on liver stiffness measurements (LSMs) and FibroScan-aspartate aminotransferase (FAST) scores using VCTE, alongside measurements such as platelet count, diabetes status, age, and sex, to identify the presence of advanced fibrosis (Agile 3+) or cirrhosis (Agile 4).
Seung Up Kim (Yonsei University College of Medicine, Seoul, Republic of Korea) and colleagues say that their findings suggest VCTE-based scores could be “suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.”
The retrospective cohort study involved 16,603 patients (mean age 52.5 years; 57.8% men) with hepatic steatosis who had undergone VCTE examination at one of 16 tertiary referral centers in the USA, Europe, or Asia between 2004 and 2023. Hepatic steatosis was diagnosed either by histologic methods (steatosis in ≥5% of hepatocytes) or imaging. Among the participants, 34.7% had diabetes and 34.8% had hypertension.
In addition to VCTE, the researchers also calculated simple fibrosis scores and assessed other noninvasive measures, including the Fibrosis-4 index, non-alcoholic fatty liver disease fibrosis score (NFS), aspartate aminotransferase (AST) to platelet ratio index (APRI), AST to alanine aminotransferase (ALT) ratio and BARD (BMI, AST:ALT ratio, and diabetes).
Over a median follow-up of 51.7 months, 1.9% of patients developed the primary outcome of LREs, a composite of hepatocellular carcinoma (HCC; n=139), hepatic decompensation (n=209), liver transplant (n=15), and liver-related death (n=65).
The results showed that the Agile 3+ and Agile 4 scores had the highest discriminatory power in predicting LREs, with integrated area under the receiver operating characteristic curves (AUC) of 0.89 and 0.88, respectively.
When pairwise comparisons were made with histologic fibrosis staging and the other noninvasive tests, the AUC for LREs at 3 and 5 years was significantly higher for both Agile scores, ranging from 0.87 to 0.91, compared with 0.86 to 0.88 for histologic fibrosis staging and 0.66 to 0.86 for the other fibrosis tests.
Compared with LSM, the Agile scores were better, albeit not significantly, for classifying patients into those with and without LREs at 3 and 5 years according to their baseline risk in line with published cutoffs, whereas the other tests were similar or correctly classified fewer patients.
For example, for patients with a baseline Agile 3+ score below 0.451, the incidence of LREs was 0.4% at 5 years, increasing to 1.5% and 10.6% for those with scores of 0.451 to 0.678, and 0.679 or above, respectively.
Kim and associates note that “the Agile 4 score mainly improved classification of patients without LREs, while the Agile 3+ score improved the classification of events.”
The researchers explain that “[t]his is understandable as the Agile 3+ score was designed to detect advanced fibrosis and the Agile 4 score was designed to detect cirrhosis. Therefore, the Agile 3+ score may be preferable for prognostic purposes, whereas the main value of the Agile 4 score is for the diagnosis of MASLD-related cirrhosis.”
While the “difference in prognostication between the Agile scores and LSM might be marginal the Agile scores were stable over time, and changes in the scores over time provide insights that can affect clinical management,” Kim et al highlight.
Indeed, in the 10,920 (65.8%) patients who had repeat VCTE examinations at a median interval of 15 months, 81.9% had stable Agile 3+ scores and 92.6% had stable Agile 4 scores. The occurrence of LREs was 0.6 per 1000 person–years in individuals with consistently low Agile 3+ scores and 30.1 per 1000 person–years in those with consistently high scores.
Among those with a high Agile 3+ score at baseline but an intermediate score at the last assessment, the incidence of LREs decreased to 3.3 per 1000 patient–years, while regardless of baseline Agile scores and LSM, a decrease in scores of more than 20% over time was associated with “a substantial reduction in the risk of LREs,” say Kim and team. This suggests a “positive nonlinear association between changes in Agile scores or LSM and the risk of LREs,” they point out. A similar trend was also seen for Agile 4 scores.
The researchers suggest that given the lower risk for LREs associated with reduced Agile scores over time, “patients with abnormal LSM or Agile scores should consider repeated examinations before deciding on liver biopsy or treatment.”
Commenting on the research in a related editorial, Zobair Younossi (Center for Outcomes Research in Liver Disease, Washington DC, USA) agreed, saying that the current study findings support the “growing evidence that Agile 3+ and Agile 4 scores and other future noninvasive tests will replace liver biopsy in most instances.”
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JAMA 2024; doi:10.1001/jama.2024.1447
JAMA 2024; doi:10.1001/jama.2024.0799