Simple Clinical Metrics Enhance AFP to Effectively Identify Cirrhotic Patients With Complicating Hepatocellular Carcinoma at Various AFP Levels

Background: Hepatocellular carcinoma (HCC) frequently occurs in cirrhosis and closely relates to poor prognosis of cirrhotic patients. Alpha-fetoprotein (AFP) is the most widely used biomarker in HCC diagnosis but not sensitive and specific to detect HCC at low AFP levels. In order to enhance the ability of AFP to detect HCC developed on cirrhosis, we attempted to combine AFP with conventional clinical metrics to develop a simple and effective method for identifying cirrhotic patients with complicating HCC at various AFP levels. Methods: Cirrhotic patients with or without HCC hospitalized to receive therapy for the first time were recruited and their clinical data were retrospectively collected. A model for diagnosing HCC was developed with routine clinical metrics and AFP by binary logistic regression analysis and internally validated. The goodness of fit, diagnostic accuracy and clinical usefulness of the model were evaluated using a calibration curve, the area under the receiver operating characteristic curve (AUROC) and a decision curve analysis, respectively. Results: A total of 574 patients with cirrhosis mainly caused by hepatitis B were recruited in this study, including 286 cases of simple cirrhosis (LC) and 288 cases of cirrhosis with HCC (LCC) (124 AFP-negative), with an average age of 53.2 ± 12.1 years and 81.4% males. Twelve of the 19 clinical metrics (age, gender, AFP, liver function tests, serum electrolytes, and coagulation tests) significantly differed between the LC and LCC groups. A model was successfully developed with age, AFP, Na(+), Cl(−), alkaline phosphatase, and activated partial thromboplastin time, which exhibited good performance in diagnosing LCC, with an AUROC of 0.918 (95%CI 0.895–0.940), 82.3% sensitivity, 89.5% specificity, and 85.9% accuracy for all patients, which were much higher values than those for AFP [0.846 (95%CI 0.815–0.878), 72.9, 81.5, and 77.2%, respectively]. For cirrhotic patients complicated with AFP-negative HCC, the model showed an AUROC of 0.854 (95%CI 0.812–0.896), 68.5% sensitivity, 86.6% specificity, and 80.0% accuracy. A high net benefit could be obtained in clinical decision making according to the model. Conclusion: A diagnostic model combining simple clinical metrics with AFP is valuable for the identification of cirrhotic patients complicating HCC with various AFP levels.