Blood sample analysis for early-stage liver cancer detection

CLiMB cohort

Stage T1 disease: four times the detection rate of ultrasound

Among 30 participants with T1 tumors, the HelioLiver Dx test detected 40.0% compared with 10.0% for ultrasound alone.

Evidence Case · CLiMB Trial Published 2026 Clinical Case Series

Clinical question

At the earliest stage of hepatocellular carcinoma, how much difference does the choice of test make?

Among the 30 CLiMB participants with stage T1 hepatocellular carcinoma, the HelioLiver Dx test detected 40.0%, four times the 10.0% detected by abdominal ultrasound alone. Adding AFP at a 20 ng/ml cutoff brought ultrasound to 20.0%.

At a glance

Cohort at a glance

Cohort	30 CLiMB participants with T1 HCC by TNM staging
HelioLiver Dx sensitivity	40.0% (95% CI 22.7-59.4)
Ultrasound alone	10.0% (95% CI 2.1-26.5)
Ultrasound plus AFP at 20 ng/ml	20.0% (95% CI 7.7-38.6)
Relative performance	4-fold higher than ultrasound alone, 2-fold higher than ultrasound plus AFP

Background

Stage determines what a patient can be offered

The publication states that detecting HCC in early stages allows for more treatment options, including curative treatment. Five-year survival for early-stage HCC is greater than 70% (Llovet et al., Nat Rev Dis Primers 2021, as cited in the CLiMB publication). For late-stage disease, median survival is approximately 1.0 to 1.5 years. It attributes the survival benefit of early detection to the opportunity for timely initiation of potentially curative treatments, including surgical resection, ablation therapies, and, for eligible patients, liver transplantation.

Cohort

T1 in the TNM staging system means a solitary tumor smaller than 2 cm, or a solitary tumor larger than 2 cm without vascular invasion. Thirty of the 46 HCC cases in CLiMB, 65%, were T1 at the initial visit.

Findings

What the data showed

The HelioLiver Dx test detected 12 of the 30, a sensitivity of 40.0%. Ultrasound alone detected 3, a sensitivity of 10.0%. Adding AFP at the most commonly cited cutoff of 20 ng/ml brought ultrasound to 6, or 20.0%.

Across the wider trial, AFP alone at 20 ng/ml reached a sensitivity of 21.7% and at 10 ng/ml reached 32.6%. The HelioLiver Dx test also demonstrated a higher sensitivity for detecting HCC than AFP-L3%, DCP, and GALAD at the most commonly cited cutoffs for each.

Clinical interpretation

What it means at the point of care

At T1, ultrasound alone detected 10.0% of cases. Adding AFP at the 20 ng/ml cutoff brought sensitivity to 20.0%, and the HelioLiver Dx test detected 40.0%.

The publication concludes that the HelioLiver Dx test detected more early HCC lesions, based on lesion T score and lesion size, compared to other testing modalities.

Key takeaways

Three things to carry forward

Sixty-five percent of the HCC cases detected in CLiMB were stage T1 at the initial visit.
The HelioLiver Dx test detected 40.0% of T1 lesions, four times the 10.0% detected by ultrasound alone.
Adding AFP to ultrasound improved detection to 20.0%, still half the rate of the multi-analyte blood test.

Limitations

This was an exploratory post hoc analysis and the study was not powered for it. The T1 subgroup is 30 participants and the confidence intervals are wide and overlapping. HCC status and T category were determined by multiphasic MRI, which served as the study’s reference standard. Participants were not staged using Child–Turcotte–Pugh scores or the Barcelona Clinic Liver Cancer (BCLC) system, as those require additional liver function parameters that were not collected.

References

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
Singal AG, Zhang E, Narasimman M, et al. HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: a meta-analysis. J Hepatol. 2022;77:128-139.

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.

This case is shared for educational purposes only. Individual patient outcomes may vary, and clinical decisions should always be based on the complete clinical picture. The HelioLiver Dx test is a laboratory developed test intended to aid in the detection of hepatocellular carcinoma in adults at high risk. It is not a replacement for guideline-recommended surveillance imaging and it is not a diagnostic test. A positive result requires diagnostic follow-up. A negative result does not exclude the presence of hepatocellular carcinoma.

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