Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation

Abstract

Growing evidence suggests that pretransplant alpha-fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-gamma-carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow-up of 78.9 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP-L3%, and DCP in a blinded fashion with the μTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9–6.7; P < 0.001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4–5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3–12.0; P < 0.001) when AFP ≥ 250 ng/mL and DCP ≥ 7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4–4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0–24.6; P < 0.001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8–18.1; P < 0.001) for outside the Milan criteria and DCP ≥ 7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility.

Hepatocellular Carcinoma Recurrence After Liver Transplantation: An Analysis of Risk Factors and Incidence from Oregon Health Science University

“…Research by Varona et al (2015) supplements the argument made by Chaiteerakij et al (2015), in terms of the AFP biomarker. These two studies agree that biomarkers should be used in addition to criteria methods, but the studies propose different levels of AFP as the indicator of recurrence.…”

“…Research performed by Fisher et al (2007), Bonadio et al (2015), and Kornberg et al (2015) identified higher incidence, reported at 18%, 22%, and 23.3%, respectively. The third range of incidence was significantly higher, with Chaiteerakij et al (2015) reporting 32%. No consensus is given for an exact range of incidence, but research suggestions a common range of 6 to 20%, with outliers of 30% or more.…”

“…These studies concentrate on the analysis of tumor criteria, through comparison of preoperative tumor characteristics and the incidence of recurrence. Research studies performed by Bonadio et al (2015) and Chaiteerakij et al (2015) analyzed the predictive capacity of the Milan, UCSF and Asan criteria. Both studies demonstrated a relationship between patients "outside" the criteria and the incidence of recurrence.…”

“…In addition to criteria analysis, Chaiteerakij et al (2015) proposed that preoperative biomarkers, specifically AFP and des-gamma-carboxyprothrombin (DCP), should be used in recurrence predictions. Research by Varona et al (2015) supplements the argument made by Chaiteerakij et al (2015), in terms of the AFP biomarker.…”

“…These two studies agree that biomarkers should be used in addition to criteria methods, but the studies propose different levels of AFP as the indicator of recurrence. Chaiteerakij et al (2015) proposed a level ≥ 250 ng/mL, while Varona et al (2015) proposed a lower level of ≥ 100 ng/mL. A study by Berry and Ioannou (2013) proposed an even lower level of ≥ 15ng/mL.…”