Recombinant alpha-fetoprotein(Merrimack Pharmaceuticals, Inc.)

Abdominal ultrasound every 6 months with or without serum alpha-fetoprotein (AFP) is recommended for hepatocellular carcinoma (HCC) screening in patients with cirrhosis. However, high-quality evidence demonstrating that this screening strategy reduces HCC-related mortality in cirrhosis is lacking. Dynamic contrast-enhanced abbreviated MRI (DCE aMRI) protocols for HCC screening have nearly identical performance to full multiphasic MRI (the gold standard for HCC diagnosis) and can be completed in under 15 min. PREMIUM is a multicentre randomised controlled trial comparing HCC screening by ultrasound+AFP every 6 months vs. DCE aMRI+AFP every 6 months for up to 8 years among patients with cirrhosis. Sponsored by and executed within the Department of Veterans Affairs (VA), participant recruitment began in November 2023. Eligible participants are Veterans aged 18-75 years with cirrhosis, high HCC risk, Child-Turcotte-Pugh (CTP) score ≤9, model for end-stage liver disease (MELD) score ≤20, and no MRI contraindications or life-threatening comorbidities. The DCE aMRI protocol consists of T1-weighted axial pre-contrast and DCE sequences (arterial, portal, and 5-minute delayed) following administration of extracellular gadolinium-based contrast agent, plus a T2-weighted sequence between portal and delayed phases. PREMIUM aims to randomise 4,700 participants (2,350 in each arm), who will undergo per-protocol imaging and follow-up for up to 8 years. The primary outcome is HCC-related mortality. Secondary outcomes include HCC stage at diagnosis, receipt of potentially curative HCC treatment, and all-cause mortality. The study is powered to detect at least a 35% relative reduction in HCC-related mortality in the aMRI+AFP arm vs. the ultrasound+AFP arm. If PREMIUM demonstrates reduced HCC-related mortality in the aMRI+AFP arm, it could provide the necessary evidence to recommend aMRI+AFP for HCC screening in patients with cirrhosis (ClinicalTrials.gov identifier: NCT05486572). The PREMIUM Study is a registered clinical trial: NCT05486572.

This study aimed to explore the efficacy and prognostic value of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment.

Relationships between the baseline levels of AFP and DCP and the clinical characteristics of 314 patients with HCC who underwent TACE were retrospectively analyzed. Kaplan–Meier curves and Cox regression models were used to analyze the survival data.

Before TACE, the patient distribution was as follows: 180 were positive for both AFP and DCP, 37 were negative for both, 24 were positive for AFP only, and 73 were positive for DCP only. Of the 131 patients included in the follow-up study after TACE treatment, 47 (35.88%) belonged to the AFP and DCP double-response group, 38 (29.01%) to the single-response group, and 46 (35.11%) to the no-response group. The overall objective response rate was significantly higher in the double- and single-response groups than in the no-response group ( P < 0.001). The overall survival (OS) and progression-free survival (PFS) rates in the double-response group were significantly longer than those in the other two groups ( P < 0.001). The response types of AFP and DCP were independent risk factors for PFS ( P = 0.003) and OS ( P = 0.007).

The combination of AFP and DCP provides a valuable serum biomarker for assessing the efficacy of TACE in patients with HCC. The goal for TACE treatment in dual-positive patients is to achieve a dual response for AFP and DCP.