Alpha-fetoprotein (AFP) testing in combination with ultrasound improves detection of early-stage liver cancer by as much as 40%, according to a meta-analysis of 32 studies comprising 13,367 patients (Gastroenterology 2018; Ultrasound alone had a 45% sensitivity in detecting early-stage disease, while ultrasound and AFP testing had a 63% sensitivity. Based on these results, the authors suggest that this two-test strategy might be the preferred surveillance approach for patients with cirrhosis.

Detecting liver cancer in earlier stages improves survival in patients with cirrhosis, but which surveillance strategy best balances early detection, surveillance-related harms, and cost-effectiveness is not clear. Professional society guidelines recommend surveillance ultrasound every 6 months but disagree about the utility of AFP testing. In pooled sensitivity analyses ultrasound has high sensitivity and specificity for detecting hepatocellular carcinoma (HCC) at any stage, but both sensitivity and specificity drop in analyses that consider only early-stage detection. There has been debate about the utility of AFP testing, but clinical studies comparing its use in combination with ultrasound have been inconclusive.

Most studies considered in the meta-analysis evaluated a single AFP cutoff value of 20 ng/mL. Studies have suggested that longitudinal patterns of AFP results increase their diagnostic accuracy, according to the authors. “Increasing AFP levels, even if below a cut-off of 20 ng/mL, can be a sign of HCC and stable or decreasing AFP levels, even if above 20 ng/mL, are reassuring,” they wrote.