A New Laboratory-Based Algorithm to Predict Development of Hepatocellular Carcinoma in Patients With Hepatitis C and Cirrhosis

Abstract

Background & Aims Serum levels of α-fetoprotein (AFP) are influenced not only by the presence of hepatocellular carcinoma (HCC) but also by underlying severity and activity of liver disease, which is reflected by liver function tests. We constructed an AFP-based algorithm that included these factors to identify patients at risk for HCC, and tested its predictive ability in a large set of patients with cirrhosis. Methods We used the national Veterans Administration hepatitis C virus (HCV) clinical case registry to identify patients with cirrhosis, results from at least 1 AFP test, and 6 months of follow up. Our algorithm included data on age; levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, albumin, creatinine, and hemoglobin; prothrombin time; and numbers of platelets and white cells. We examined the operating characteristics (calibration, discrimination, predictive values) of several different algorithms for identification of patients who would develop HCC within 6 months of the AFP test. We assessed our final model in the development and validation subsets. Results We identified 11,721 patients with HCV-related cirrhosis in whom 35,494 AFP tests were performed, and 987 patients developed HCC. A predictive model that included data on levels of AFP, ALT, and platelets, along with age at time of AFP test (and interaction terms between AFP and ALT, and AFP and platelets), best discriminated between patients who did and did not develop HCC. Using this AFP-adjusted model, the predictive accuracy increased at different AFP cutoffs, compared with AFP alone. At any given AFP value, low numbers of platelets and ALT and older age were associated with increased risk of HCC, whereas high levels of ALT and normal/high numbers of platelets were associated with low risk for HCC. For example, the probabilities of HCC, based only on 20 ng/ml and 120 ng/ml AFP, were 3.5% and 11.4%, respectively. However patients with the same AFP values (20 ng/ml and 120 ng/ml) who were 70 y old, with ALT levels of 40 IU/ml and platelet counts of 100,000, had probabilities of developing HCC of 8.1% and 29.0%, respectively. Conclusions We developed and validated an algorithm based on levels of AFP, platelets, and ALT, along with age, which increased the predictive value for identifying patients with HCV-associated cirrhosis likely to develop HCC within 6 months. If validated in other patient groups, this model would have immediate clinical applicability.

Surveillance of Hepatocellular Carcinoma and Diagnostic Algorithms in Patients with Liver Cirrhosis

“…High AFP levels are also observed in cirrhosis with high inflammatory activity and may correlate with aminotransferase levels [36,37]. A cut-off value of 20 ng/ml was shown to optimally level sensitivity and specificity of AFP; however, sensitivity remained at only 60% [38,39]. Of note, reducing the cut-off resulted in a considerable number of false-positive findings which would require additional and, frequently, unnecessary tests.…”

Screening for Hepatocellular Carcinoma and Cholangiocarcinoma: Can Biomarkers Replace Imaging?

“…Their model-predicted probability levels showed a very close relationship with raw frequencies of HCC that only deviated in risks higher than 90% where there is no practical significance. This model is yet to be tested on other populations with liver disease due to causes other than HCV and in populations outside of the Veterans Affair (VA) Health system where males predominate 20 . The recently published ADRESS model can be used for predicting HCC probability in patients with cirrhosis using the variables of age, diabetes, race, cirrhosis etiology, sex and severity of liver dysfunction.…”

The 6th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2015), Evidence and Consensus on HCC Management. Osaka, Japan, July 3-5, 2015: Abstracts

“…El Serag et al [9] have developed a score taking advantage of the fact that false-positive AFP values are associated with active hepatic inflammation. Therefore an elevated AFP in the presence of elevated ALT is less likely to be associated with HCC than if the ALT was normal.…”