TOPLINE:

In patients at high risk for hepatocellular carcinoma (HCC), adding the serum biomarkers alpha-fetoprotein (AFP), the lectin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) to biannual ultrasound-based surveillance did not improve the early detection of the condition.

METHODOLOGY:

• HCC is often detected at advanced stages, and 6-monthly ultrasound has limited sensitivity for early tumors, particularly in people with cirrhosis or obesity. Therefore, better surveillance tools are needed for the early diagnosis of HCC.
• Researchers conducted a randomized controlled trial to assess whether adding serum biomarkers to ultrasound surveillance improved the early-stage detection of HCC in patients at high risk for the condition.
• They included adult patients with cirrhosis or high-risk hepatitis B at two Toronto-based hospitals between 2014 and 2020. Patients were randomly assigned to undergo ultrasound alone or ultrasound plus analysis of three serum biomarkers (AFP, AFP-L3, and DCP).
• A positive ultrasound was defined as any new liver nodule > 0.8 cm, any lesion that increased in size by > 30%, or an increase in the number of existing nodules. A positive biomarker result was an AFP level > 100 ng/mL (or a doubling with a follow-up value ≥ 60 ng/mL), an AFP-L3 level > 10%, or a DCP level > 2 ng/mL; positive results prompted CT or MRI for confirmation.
• The primary endpoint was the proportion of HCCs diagnosed at an early stage (Barcelona Clinic Liver Cancer stage 0-A). Patients underwent biannual surveillance for a minimum of 2 years and up to 6 years.

TAKEAWAY:

• The trial included 1208 patients (mean age, 58.4 years; 71.8% male). Of these, 603 were assigned to undergo ultrasound alone and 605 to undergo ultrasound with analysis of biomarkers.
• During the follow-up period, 62 patients (5.1%) developed HCC. The incidence rate of early-stage HCC was 1.2 per 100 person-years, and the rate of detection did not differ between the groups.
• The incidence rate of late-stage HCC was 0.22 per 100 person-years and did not differ between the groups.
• Biomarkers alone detected five early-stage HCCs and one late-stage HCC missed by ultrasound.

IN PRACTICE:

“Because HCCs were detected by BMs [biomarkers] in some patients with a corresponding negative US [ultrasound], there may be a role for BMs in some patients; however, determining optimal thresholds or using a combination of BMs with other clinical parameters and identifying specific patient populations will be vital to improving early-stage HCC detection using BMs,” the authors of the study concluded.

SOURCE:

The study was led by Grishma Hirode, PhD, and Hooman F. Zangneh, MD, Toronto General Hospital, Toronto, Ontario, Canada. It was published online in Gastroenterology.

LIMITATIONS:

The study was conducted at a tertiary referral center with expert operators; thus, the results may not be applied to general practice. The study was underpowered because HCC incidence was lower than expected. Adherence to the study protocol was worse in the biomarker group.

DISCLOSURES:

The study received financial support from FUJIFILM Wako Pure Chemical Corporation; all serum biomarkers were analyzed using a device developed by that company. Three authors reported receiving grants from and/or serving as consultants for several pharmaceutical, biotechnology, and healthcare companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.