Binu John, MD, MPH, is an associate professor of medicine and chief of gastroenterology and hepatology at the University of Miami

Binu John, MD, MPH

ALTUS: Multi-Target Blood Outperforms Ultrasound for HCC, With John Binu, MD, MPD

A new multi-target blood test (mt-HBT), Exact Sciences’ Oncoguard® Liver blood test, delivers superior early-stage and overall sensitivity for hepatocellular carcinoma (HCC) compared to standard of care abdominal ultrasound, according to findings from the prospective multicenter ALTUS study.

Binu John, MD, MPH, an associate professor of medicine and chief of gastroenterology and hepatology at the University of Miami, presented the data at the 

American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025

, reporting the higher sensitivity demonstrated by mt-HBT for detecting early-stage HCC, defined by Milan Criteria, in at-risk patients (66.7%) compared with ultrasound (22.2%).

HCC imposes a major global health burden, with mortality rates continuing to rise by 2-3% annually. Since advanced HCC is largely considered incurable, early diagnosis is critical. At the early stage, surgical resection has 5-year survival rates of >70%. Poor prognosis and high mortality directly correlate with limited surveillance and insufficient diagnostic precision, yet the tools clinicians rely on for early HCC detection continue to face challenges in sensitivity and specificity, particularly in patients with comorbidities.

Ultrasound screening achieves roughly 84% overall accuracy for HCC diagnosis across all stages, but only 47%-63% accuracy for early-stage disease detection in patients with cirrhosis. In addition, obesity further reduces imaging visibility, contributing to lower sensitivity in ultrasound surveillance.2

“We have long known [ultrasound] is not a great test because the test is not very sensitive. It does not work very well in obese patients,” John said in an interview with 

 “The most common cause of liver disease now is metabolic-associated steatotic liver disease, and in those patients, ultrasound is not good at finding lesions, especially small lesions. Our target population is patients with cirrhosis, and their liver is nodular, so you can easily miss small nodules too.”

Coined as the largest prospective, real-world trial of a blood test for liver cancer surveillance in the United States, ALTUS enrolled adults with cirrhosis (92.9%) or chronic hepatitis B virus infection. Participants underwent standard-of-care HCC surveillance (92.9% ultrasound, 7.1% CT/MRI) and concurrent mt-HBT testing. 

Key endpoints were early-stage HCC sensitivity and overall specificity in a non-inferiority comparison to ultrasound. HCC was defined by central radiology adjudication of LI-RADS 5 or tumor-in-vein observations by two blinded, independent radiologists, or by pathology, through a combination of DNA methylation markers, AFP levels, and patient sex, highlighting a breakthrough in early diagnosis surveillance.

Of the 3089 participants enrolled, the 2467 (79.9%) who were evaluable had a mean age of 63.1 years, 42.8% female, and 20.5% Hispanic. Among the cirrhosis etiologies, metabolic-associated steatotic liver disease (40.5%), alcohol-related liver disease (27.7%, hepatitis C virus (14.0%), and hepatitis B virus (2.2%) were the most common. Investigators identified 40 HCCs, including 28 early-stage cases.

In detecting early-stage HCC, investigators observed higher sensitivities for mt-HBT (66.7%; 95% Confidence Interval [CI], 47.8–81.4) compared to ultrasound (22.2%; CI, 10.6–40.8; 

 =.002). Similarly, overall HCC sensitivity for mt-HBT surveillance was 70.0% (CI, 54.6–81.9), 29.7% (CI, 17.5–45.8) for ultrasound, and 52.6% for ultrasound combined with alpha-fetoprotein (AFP) ≥20 ng/mL (CI, 37.3-67.5).

Investigators saw no significant difference in each surveillance method for specificity: 81.9% for mt-HBT (CI, 80.3-83.4), 98.6% for ultrasound (CI, 98.0-99.0), and 97.7% for ultrasound + AFP (CI, 96.9-98.2). Additionally, mt-HBT sensitivities did not significantly differ by tumor size of <2cm (58.3%; CI, 32.0-80.7); 2-5cm (78.3%; CI, 58.1-90.3), or >5cm (75.0%; CI, 30.1-95.4).

“Hepatologists are going to embrace this test because the sensitivity difference is incredible, and they are always looking for early-stage cancer. [mt-HBT] is very convenient and easy to adapt in the clinic,” said John. “Combining all these advantages, I believe the hepatology community is going to embrace this. It’s going to make a big difference in helping our patients with liver cancer diagnose their disease early.”

Editors’ Note: John reports relevant disclosures with Exact Sciences, Genentech, Glycotest, and Takeda.

Performance of a Multi-Target Blood Test Versus Ultrasound in Detecting Early Hepatocellular Carcinoma: Results from the ALTUS Prospective Study.

 Abstract presented at: American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025; November 7-11, 2025; Washington, DC.

Exact Sciences Announces Breakthrough Results from Landmark Study. Exactsciences.com. Published 2025. Accessed November 10, 2025. 

https://www.exactsciences.com/news-events/press-releases/exact-sciences-announces-breakthrough-results-from-landmark-study

Wang W, Wei C. Advances in the early diagnosis of hepatocellular carcinoma. 

https://doi.org/10.1016/j.gendis.2020.01.014

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ALTUS findings presented at AASLD show mt-HBT detects early-stage HCC with >66% higher sensitivity than ultrasound, addressing gaps in liver cancer surveillance.


Binu John, MD, MPH

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