HCC surveillance in hepatitis C: A longitudinal algorithm improves alpha-fetoprotein screening

Surveillance for HCC remains important after hepatitis C cure. Improved sensitivity of screening with alpha-fetoprotein (AFP) by using a parametric empirical Bayes (PEB) algorithm, which incorporates an individual patient's longitudinal AFP measurements, was previously demonstrated in a retrospective analysis of clinical trial data prior to widespread hepatitis C cure.

We analyzed de-identified data extracted from the medical records of participants in the Alaska Hepatitis C Study, which aims to enroll all Alaska Native persons living in Alaska with a history of hepatitis C.We compared the performance characteristics of AFP as a screening test using the PEB method versus a fixed cutoff (FC) method in an observational setting, separately for HCC surveillance in active and cured hepatitis C.

The PEB and FC methods were applied to AFP levels from participants with F3/F4 fibrosis who had active hepatitis C (173 no HCC, 14 HCC) or after they achieved hepatitis C cure (162 no HCC, 12 HCC). Compared to a fixed 20 ng/mL cutoff, demonstrating 91.2% specificity in active hepatitis C, PEB increased sensitivity from 64.3% to 71.4%. After cure, a fixed 7.2 ng/mL cutoff demonstrated 91.2% specificity, and PEB increased sensitivity from 58.3% to 91.7%.

The PEB algorithm can increase sensitivity and lead to earlier detection of HCC among patients with F3/F4 fibrosis, both in active and even more so in cured hepatitis C. Lower AFP levels after cure indicate that for either PEB or FC methods, screening parameters, such as cutoffs for a target specificity, should be specified separately by hepatitis C treatment status for HCC surveillance.