DAY 3: Accurate Diagnosis of Compensated Cirrhosis Relies on Complementary Evidence

A multimodal approach combining different noninvasive screening tools with etiology-specific thresholds may increase diagnostic certainty, ensuring timely management of patients with compensated cirrhosis. Data presented at the 2026 Annual Scientific Meeting of the American College of Gastroenterology showed that commonly used noninvasive tests designed to assess different features of liver disease may yield different results in different populations, and may not uniformly identify compensated cirrhosis. 

“Diagnosing cirrhosis increasingly relies on multiple sources of evidence,” Nicole Welch, MD, a gastroenterologist affiliated with the Cleveland Clinic in Ohio, remarked during a plenary session. “Biopsy, conventional imaging, liver stiffness measurements, and blood-based noninvasive liver disease assessments evaluate different features of the disease, and no single assessment captures the entire phenotype of compensated cirrhosis. Current guidance, therefore, emphasizes interpreting these tests within the appropriate population, disease etiology, and clinical context. Importantly, a value below a single threshold does not necessarily exclude compensated cirrhosis.” Welch noted that blood-based scores and liver stiffness measurements do not assess the same feature of liver disease. Moreover, commonly used thresholds were developed for different populations and clinical purposes. In practice, this may lead to a paradox where selecting different modalities and cutoffs may yield different results when assessing the same patient. “That discordance can create uncertainty when we are trying to establish a diagnosis of compensated cirrhosis,” Welch added. 

Welch and colleagues designed a cross-sectional analysis of data from the prospective, multicenter Liver Cirrhosis Network Cohort Study to evaluate the degree of concordance between different noninvasive assessment modalities. The analysis included 1,199 adults with compensated cirrhosis enrolled at 10 U.S. clinical sites, with a median age of 62 years. Approximately half (51%) of the cohort had MASLD. Eligibility was established based on liver biopsy findings that were consistent with cirrhosis or by meeting at least two prespecified non-biopsy criteria. “An important feature of this cohort is that cirrhosis was not defined by any one of the noninvasive assessments that we evaluated in this analysis,” Welch said. 

The researchers looked at various types of noninvasive tests, including liver stiffness measurements and blood-based assessments. Liver stiffness was measured by vibration-controlled transient elastography (VCTE) or magnetic resonance elastography (MRE). Blood-based assessments included the Fibrosis-4 (FIB-4) index, platelet counts, and the aspartate aminotransferase to platelet ratio index (APRI). The Agile 4 score, combining physical measurements and routine laboratory values, was also evaluated as a composite measure.  

The analysis revealed that the relationships between different assessment modalities were heterogeneous rather than uniform. “We saw stronger relationships within some groups of tests, particularly among the blood-based measures, and more modest relationships across modalities. The two liver stiffness measures were moderately correlated, and Agile 4 showed moderate correlation with VCTE. In contrast, the liver stiffness measures showed relatively low correlation with the individual blood-based assessments. Platelet count, as expected, showed an inverse relationship with several of the other measures.” The strength and direction of the correlation depended on the pair of noninvasive assessments and did not necessarily translate into a confirmation of diagnosis.

Overall, MRE and Agile 4 showed greater concordance with one another than APRI did with most other assessments. VCTE–MRE agreement decreased when the higher MRE threshold was applied. “Commonly used cirrhosis thresholds identified overlapping but clearly nonidentical patient populations,” Welch explained, noting that the analysis did not identify a single, optimal test. Future analyses that may stratify patients by body mass index and different etiologies could identify optimal thresholds, Welch said. 
“These findings support a multimodal approach to cirrhosis diagnosis and further work to define the optimal combinations [of assessment modalities] and thresholds for clinical use,” Welch concluded. “Ultimately, the goal is to define clinically useful combinations of noninvasive assessments and more appropriate, etiology-specific thresholds.”