Abstract
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.
Highlights
Liver cancer, mainly hepatocellular carcinoma (HCC), was estimated to be the sixth most frequent cancer and the fourth cause of cancer death worldwide in 2018, with appropriately 841,000 new cases and 782,000 deaths annually [1]; the incidence of HCC has been increasing in the past two decades and is expected to increase until 2030 in some countries, including the United States
Based on the training set, a diagnostic model to identify cirrhotic patients complicated with HCC was successfully developed with six variables (Table 3), which had a Nagelkerke R2 of 0.660 and a p-value of 0.718 in the Hosmer-Lemeshow test
A diagnostic model incorporating AFP and five clinical metrics was developed and internally validated to identify cirrhotic patients complicated with HCC
Summary
Mainly hepatocellular carcinoma (HCC), was estimated to be the sixth most frequent cancer and the fourth cause of cancer death worldwide in 2018, with appropriately 841,000 new cases and 782,000 deaths annually [1]; the incidence of HCC has been increasing in the past two decades and is expected to increase until 2030 in some countries, including the United States. According to the 2018 Practice Guidance by the American Association for the Study of Liver Diseases [5], the modality recommended for HCC surveillance in cirrhotic patients is ultrasound, with or without alpha-fetoprotein (AFP), every 6 months, indicating that AFP is not as important as ultrasound for HCC surveillance. The surveillance strategy of combining AFP and ultrasound examinations at 6-month intervals is estimated to detect more than triple the number of patients with operable HCC tumors at the time of diagnosis and reduce almost half the number of deaths from HCC compared with no surveillance [6]. Hepatocellular carcinoma (HCC) frequently occurs in cirrhosis and closely relates to poor prognosis of cirrhotic patients. 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
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