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

Abstract

Background & Aims Little information is available about what factors determine serum levels of α-fetoprotein (AFP) levels (e.g., demographic, virological, or clinical features) among individuals who do not develop hepatocellular cacrcinoma (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 that 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.

Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B

“…One of the methodological strengths of this study is analysis of all consecutive AFP measurements from each patient instead of single representative AFP values, which might introduce bias because AFP levels frequently fluctuate in chronic viral hepatitis patients with hepatitis flare-up, hepatic fibrosis and hepatic dysfunction (S1 Fig) [9, 10, 21, 24, 35, 36]. More importantly, matching of all serial AFP values with concomitantly measured covariates allowed identification of covariates for AFP elevation and for AFP performance in the whole surveillance periods.…”

Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis

“…In a further meta-analysis including ten studies the pooled sensitivity of AFP for the diagnosis of HCC was 51.9% at a specificity of 94% (AUC = 0.81) [25] . It is a major drawback of AFP as surveillance tool that its serum levels are influenced by the activity of the underlying liver disease and therefore increased in patients with elevated ALT levels even in the absence of HCC as shown in the HALT-C trial [26] .…”

Relationship between Serum Hyaluronic Acid Level and Patient Prognosis in Hepatocellular Carcinoma Patients Who Underwent Hepatectomy

“…If the serum HA level correlates tumor development, the mechanism of tumor progression would be different from that of adenocarcinomas. However, the AFP level might be correlated with the degree of chronic hepatitis [38]. Measurement of the level of AFP was not a good indicator of liver injury; measurement of HA levels was more reliable to predict liver injury and patient survival.…”