Utility of Serum Biomarkers in Addition to Ultrasound for Early Detection of Hepatocellular Carcinoma in High-Risk Patients: A Randomized Controlled Trial.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance is key to early diagnosis and timely curative treatment. Current strategies are suboptimal with many patients presenting with advanced HCC. This randomized controlled trial compared the combined use of serum biomarker (BM) measurements and abdominal ultrasound (US) with US alone for the diagnosis of early-stage HCC.

METHODS

Adults with cirrhosis or high-risk hepatitis B virus (HBV) infection were randomized (1:1) to biannual surveillance with US alone (group A) or US and BMs (group B) in blocks of 2 or 4. Positive US results or elevated BMs (α-fetoprotein [AFP] >100 ng/mL, lectin-reactive fraction of AFP [AFP-L3] >10%, des-gamma-carboxy prothrombin [DCP] >2 ng/mL) triggered further imaging for HCC confirmation. Primary end point was proportion of early-stage HCCs.

RESULTS

There were 1208 patients randomized (n = 603 group A, n = 605 group B). Mean ± SD age was 58.4 ± 9.8 years, 71.8% were male, 55.1% were Asian, 64.0% had HBV, and 64.3% had cirrhosis. During follow-up, 35 HCCs (5.8%) developed in group A (n = 30 early-stage, n = 5 late-stage) and 27 (4.5%) developed in group B (n = 22 early-stage, n = 5 late-stage). Early-stage HCC incidence was 1.2 per 100 person-years with cumulative probabilities of 1.3% at 52 weeks and 5.9% at 260 weeks. Early-stage HCC detection rate did not differ by study arm (hazard ratio, 0.81; 95% CI, 0.47-1.40; P = .45). In group B, elevated AFP-L3 was equally effective compared with using all 3 BMs.

CONCLUSIONS

Addition of AFP, AFP-L3, and DCP to biannual US did not improve early-stage HCC detection. The trial was not adequately powered to provide evidence that the use of BMs aside from US plus AFP improves HCC surveillance. Establishing and validating alternative approaches to incorporation of BMs may improve surveillance methods for early-stage HCC detection.

CLINICALTRIALS: gov, Number: NCT02272504.