Prothrombin-induced by vitamin K absence II as a prognostic factor in living donor liver transplantation for hepatocellular carcinoma
Abu Bakar Hafeez Bhatti, Usman Shafique, Nazish Ahmed, Ghazanfar Abbas, Muslim Atiq, Haseeb Zia, Nusrat Yar Khan, Atif Rana
Abstract
In hepatocellular carcinoma (HCC), there is a need for novel tumor markers to enhance patient selection for liver transplantation. This study evaluates the prognostic value of Prothrombin Induced by Vitamin K Absence-II (PIVKA-II) in predicting microvascular invasion (MVI) and post-transplant recurrence, either alone or in combination with alpha-fetoprotein (AFP), following living donor liver transplantation (LDLT). We reviewed 400 patients who underwent LDLT under expanded criteria (largest tumor diameter ≤ 10 cm, any tumor number, AFP < 1000 ng/ml). PIVKAII outperformed AFP and tumor size in predicting MVI, with a C-statistic of 0.777 compared to 0.579 and 0.631. On multivariate analysis, AFP > 20 ng/ml [HR 3.3, P = 0.003] and PIVKAII > 1000 mAU/ml [HR 3.5, P = 0.001] were predictors of recurrence. PIVKAII > 1000 mAU/ml was associated with MVI (21.6% vs. 65.7%, P < 0.001) and lower 5-year RFS (79% vs. 50%, P < 0.001). A combination of AFP > 20 ng/ml and PIVKAII > 1000 mAU/ml predicted 47.1% of recurrences, whereas HCC recurred in 6.1% of patients not meeting this threshold. The 5-year RFS was 45% for dual tumor marker positive HCC versus 77% for all others (P < 0.001). PIVKAII is a strong predictor of MVI and post-transplant recurrence. Dual tumor marker-positive HCC can serve as an exclusion criterion for upfront LDLT.