Evaluation of Ferritin and Transferrin Ratio as a Prognostic Marker for Hepatocellular Carcinoma

Abstract

Purpose of the study: Hepatocellular carcinoma (HCC) has tripled in incidence over the past 20 years and now ranks as the third leading cause of mortality attributed to cancer. Underlying pathophysiology is sustained hepatic inflammation which results in hepatocellular dysplasia and thus an environment prone to HCC. Considering the essential role of inflammation in the pathogenesis of HCC, we evaluated the prognostic utility of ferritin-transferrin ratio (FTR) in HCC.

Methods: We retrospectively reviewed the electronic medical records of patients with HCC (diagnosed on radiographic criteria and/or biopsy) from 2000 through 2015. We collected data regarding the patient demographics, laboratory investigations at the time of HCC diagnosis and prior to the initiation of treatment. Overall survival was calculated from the time of diagnosis, cases were censored at the date of last follow-up, if date of death was not known. Kaplan-Meier curves were estimated to evaluate the prognostic significance of FTR. Receiver operating characteristics (ROC) curve was plotted for FTR to predict mortality and identify cut-off value by optimized Youden's index.

Results: Among the 176 patients identified by initial screening, 116 patients were eventually included for analysis. Overall median survival was 11.9 months. FTR, of note, was significantly lower in alive (6.9, p < 0.001). In univariate analysis, alfa-fetoprotein (AFP), aspartate aminotransferase (AST), serum ferritin (SF), transferrin (TFS), and FTR were significantly associated with mortality. On multivariate analysis for mortality, FTR, AFP, and epidemiologic factors predictive of mortality including male gender and advanced HCC were significant.

Conclusion: The ferritin-transferrin ratio (FTR), calculated at the time of HCC diagnosis could predict mortality in our cohort of patients. With an optimal cut-off of 7.7 for FTR were stratified into high- and low-risk groups. The hazard ratio between the two groups was 2.36 (p < 0.003). Future studies with longitudinal follow-up of FTR at intervals and important time points (e.g., perioperative) might provide more insights to its prognostic value.

Keywords: AFP; FTR; Ferritin transferrin ratio; HCC; SF; Serum ferritin; Transferrin TFS.