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Alpha-fetoprotein improves early detection of liver cancer with cirrhosis

Magnetic resonance imaging alone to detect early-stage hepatocellular carcinoma had a low level of sensitivity among patients with cirrhosis, according to a recently published meta-analysis. However, ultrasound with alpha-fetoprotein significantly increased the sensitivity of HCC detection.

“We demonstrated ultrasound has suboptimal sensitivity for early HCC detection, highlighting the need for alternative surveillance strategies,” Kristina Tzartzeva, MD, from the University of Texas Southwestern Medical Center, and colleagues wrote. “Using AFP in combination with ultrasound significantly increases early HCC detection, suggesting this may be the preferred surveillance strategy for patients with cirrhosis until superior surveillance strategies are available.”

Tzartzeva and colleagues selected 32 studies from a database review as part of a meta-analysis. The studies included a total of 13,367 patients, 1,877 of whom developed HCC. In the 15 studies that reported data on early HCC, researchers detected HCC early in 319 of 516 patients who developed cancer. Twenty-eight studies exclusively included patients with cirrhosis.

The meta-analysis revealed a wide range in sensitivities for any stage detection of HCC (28%-100%) and for early detection (21%-89%). Pooled sensitivity for detection at any stage was 84% (95% CI, 76-92) and 47% for early detection (95% CI, 33-61).

In a subset review of studies that reported sensitivity and specificity of ultrasound, area under the curve for any stage detection of HCC was 0.96 (95% CI, 0.94-0.98). Area under the curve was significantly lower for early detection (AUC = 0.88; 95% CI, 0.85-0.9). At any stage, pooled sensitivity was 53% (95% CI, 35-70) and specificity was 91% (95% CI, 86-94). The positive likelihood ratio of ultrasound for early stage HCC was 5.8 (95% CI, 3.7-9.2) and the negative likelihood ratio was 0.51 (95% CI, 0.35-0.75), with a diagnostic odds ratio of 11 (95% CI, 5-24).

Tzartzeva and colleagues found 18 studies that compared sensitivity of ultrasound with or without AFP. For detection of HCC at any stage, sensitivity of ultrasound alone was 75% (95% CI, 67-86) compared with 97% (95% CI, 91-99) for ultrasound with AFP. Ultrasound alone had a significantly lower sensitivity (RR = 0.88; 95% CI, 0.83-0.93).

Among the seven studies that compared sensitivity of ultrasound alone compared with ultrasound and AFP for early detection of HCC, the pooled sensitivity of ultrasound alone was 63% (95% CI, 48-75) compared with 45% (95% CI, 30-62) for ultrasound with AFP. Ultrasound alone had a significantly lower sensitivity (RR = 0.81; 95% CI, 0.71-0.93).

“There has been considerable debate regarding the potential benefit of adding AFP to ultrasound-based HCC surveillance programs,” Tzartzeva and colleagues wrote. “A previously attempted randomized controlled trial comparing ultrasound alone to ultrasound with AFP was not possible given high rates of AFP contamination in the ultrasound alone study arm, highlighting providers’ reluctance to not perform AFP and rely on ultrasound alone. This also underlines the importance of our study’s findings, as this meta-analysis of cohort studies may represent the highest level of evidence possible comparing the two surveillance tests.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.