MASLD and obesity, where ultrasound sensitivity is reduced
Half of the HCC cases in CLiMB had MASLD, and 55% of the study population was obese. Across every etiology of cirrhosis evaluated, the HelioLiver Dx test showed a higher sensitivity than the comparator modalities.
How does HCC detection perform across etiologies of cirrhosis, including MASLD?
MASLD was the single largest etiology among CLiMB participants with HCC, present in half of them, and 55% of the study population was obese. Across every etiology of cirrhosis evaluated, the HelioLiver Dx test demonstrated higher sensitivity than the comparator modalities.
Cohort at a glance
| HCC cases with MASLD | 23 of 46, 50.0% |
|---|---|
| HCC cases with alcohol-associated liver disease | 10 of 46, 21.7% |
| HCC cases with viral etiology | 16 of 46, 34.8% |
| Obese participants, study population | 55% |
| HelioLiver Dx sensitivity across etiologies | 6.3% to 66.7% higher than other modalities |
| HelioLiver Dx specificity across etiologies | 2.3% to 11.3% lower than other modalities |
The epidemiology of liver cancer has shifted
The epidemiology of liver cancer in the United States has shifted. Incidence and mortality are rising, driven in part by an increasing burden of obesity, diabetes, and metabolic dysfunction-associated steatotic liver disease, or MASLD.
Cohort
CLiMB reflects that shift. MASLD was the single largest etiology among participants who had HCC, present in half of them, and 55% of the study population was obese, defined as a BMI over 27.5 for participants of Asian descent and over 30 for all others.
What the data showed
Across every etiology of cirrhosis evaluated, MASLD, alcohol-associated liver disease, viral, and other, the HelioLiver Dx test demonstrated higher sensitivity than the comparator modalities, by margins ranging from 6.3% to 66.7%. Specificities were 2.3% to 11.3% lower.
The publication identifies the high proportion of obese participants, 55%, as a factor known to reduce ultrasound sensitivity. Separately, it reports that the large representation of participants enrolled at community-based centers with potentially variable sonographer experience, combined with standardized central ultrasound reading and the high prevalence of small HCC lesions, may have contributed to the low observed ultrasound performance.
What it means at the point of care
The publication reports that ultrasound performance is influenced by patient characteristics, including BMI and lesion size, and by operator experience. It identifies the high proportion of obese participants in this cohort, 55%, as a factor known to reduce ultrasound sensitivity.
The HelioLiver Dx test is performed on a blood specimen analyzed in a central laboratory. Across every etiology of cirrhosis evaluated in CLiMB, it demonstrated a higher sensitivity than the comparator modalities, with specificities that were modestly lower.
The publication reports that the incidence and mortality of HCC are increasing in the United States, driven in part by an increasing burden of obesity, diabetes, and MASLD.
Three things to carry forward
- MASLD was the most common etiology among CLiMB participants with HCC, present in 50.0% of cases.
- Fifty-five percent of the study population was obese, a factor the authors identify as known to reduce ultrasound sensitivity.
- The HelioLiver Dx test showed higher sensitivity than comparator modalities across every etiology of cirrhosis evaluated.
- Taggart DJ, Mahajan S, Gallant MA, et al. A multi-analyte cfDNA-based blood test for early detection of hepatocellular carcinoma. J Hepatol. 2026;1-9. doi:10.1016/j.jhep.2026.04.012
- Younossi ZM, Otgonsuren M, Henry L, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62:1723-1730.
About the CLiMB trial
CLiMB was a cross-sectional, prospective, blinded, multicenter validation study conducted across 42 clinical sites in the United States, evaluating the HelioLiver Dx test against abdominal ultrasound for the detection of hepatocellular carcinoma in adults with cirrhosis. Multiphasic MRI served as the reference standard. The HelioLiver Dx test met prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared to ultrasound.
Enrolled vs. evaluable. A total of 1,556 patients were enrolled in the prospective CLiMB study and assigned to the validation cohort, of whom 1,285 completed the initial visit. At the 6-month follow-up visit, 17 participants were lost to follow-up and were excluded from analysis. Only participants with valid results from the HelioLiver Dx test, ultrasound, and multiphasic MRI were considered evaluable. A total of 1,268 participants (81.5%) were evaluable, including 46 participants with HCC and 1,222 participants without HCC. Every performance figure in this series is calculated on that evaluable population. Published in the Journal of Hepatology, 2026. ClinicalTrials.gov identifier NCT03694600.
Have a case to contribute?
Clinicians using the HelioLiver Dx test can submit de-identified cases for consideration in this series.