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Hepatology. 2015 Jul;62(1):158-65. doi: 10.1002/hep.27787. Epub 2015 Apr 22.

Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: A prospective validation.

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Divisions of Transplant and Abdominal Surgery, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland.
Division of Transplantation, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Multi-Organ Transplant Program, London Health Sciences Center, The University of Western Ontario, London, Ontario, Canada.
University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland.


The selection of liver transplantation (LT) candidates with hepatocellular carcinoma (HCC) is currently validated based on Milan criteria. The use of extended criteria has remained a matter of debate, mainly because of the absence of prospective validation. The present prospective study recruited patients according to the previously proposed total tumor volume (TTV; ≤115 cm(3) )/alpha-fetoprotein (AFP; ≤400 ng/mL) score. Patients with AFP >400 ng/mL were excluded, and, as such, the Milan group was modified to include only patients with AFP <400 ng/mL; these patients were compared to patients beyond Milan, but within TTV/AFP. From January 2007 to March 2013, 233 patients with HCC were listed for LT. Of them, 195 patients were within Milan and 38 beyond Milan, but within TTV/AFP. The average follow-up from listing was 33.9 ± 24.9 months. Risk of dropout was higher for patients beyond Milan, but within TTV/AFP (16 of 38; 42.1%), than for those within Milan (49 of 195 [25.1%]; P = 0.033). In parallel, intent-to-treat survival from listing was lower in patients beyond Milan (53.8% vs. 71.6% at 4 years; P < 0.001). After a median waiting time of 8 months, 166 patients were transplanted, 134 within Milan criteria, and 32 beyond Milan but within TTV/AFP. They demonstrated acceptable and similar recurrence rates (4.5% vs. 9.4%; P = 0.138) and post-transplant survivals (78.7% vs. 74.6% at 4 years; P = 0.932).


Based on the present prospective study, HCC LT candidate selection could be expanded to the TTV (≤115 cm(3) )/AFP (≤400 ng/mL) criteria in centers with at least 8-month waiting time. An increased risk of dropout on the waiting list can be expected, but with equivalent and satisfactory post-transplant survival.

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