Determinants of Serum Alpha-Fetoprotein Levels in Hepatitis C-Infected Patients

Background & Aims: Little information is available about what factors determine serum levels of alpha fetoprotein (AFP) (eg, demographic, virologic, or clinical features) among individuals who do not develop hepatocellular carcinoma (HCC). This information might improve AFP-based algorithms for HCC detection. Methods: We examined data from patients in the national Veterans' Affairs Hepatitis C Virus (HCV) Clinical Case Registry who received at least 1 AFP test (258,275 AFP tests in 76,357 patients; 1.9% developed HCC). We constructed hierarchical multivariate models of AFP levels. Potential predictors of AFP values included patients' sex, race, cirrhosis status, Model for End-Stage Liver Disease (MELD) score, HCV genotype, level of alanine aminotransferase (ALT) within 30 days before the AFP test, time to diagnosis of HCC, and time elapsed from the HCV index date. Results: Significant determinants for increased levels of AFP included presence of cirrhosis, higher MELD scores, and increased levels of ALT. AFP levels were also affected by the interaction between ALT levels and the presence and time to development of HCC. Among patients who did not have HCC, the AFP level increased with the level of ALT; the AFP values in the presence of ALT 37-56 U/L, ALT 57-92 U/L, or ALT >92 U/L were 16%, 35%, and 68% higher, respectively, than AFP values at ALT 0-36 U/L. However, patients who developed HCC within 30 days of receiving the AFP test had a lower rate of increase in AFP with each higher category of ALT level, with increases of 31%, 39%, and 37% for the same respective ALT categories. Conclusions: In patients with chronic HCV infection, AFP and ALT values correlate; however, among patients with HCC, levels of AFP increase disproportionately to or unaccompanied by increases in levels of ALT. The prognostic and diagnostic value of AFP levels might be increased by adjusting for ALT values.