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Liver Transplantation Criteria For Hepatocellular Carcinoma Should Be Expanded: A 22-Year Experience With 467 Patients at UCLA

Duffy, John P. MD; Vardanian, Andrew MD; Benjamin, Elizabeth MD, PhD; Watson, Melissa MD; Farmer, Douglas G. MD; Ghobrial, Rafik M. MD, PhD; Lipshutz, Gerald MD; Yersiz, Hasan MD; Lu, David S. K. MD; Lassman, Charles MD; Tong, Myron J. MD, PhD; Hiatt, Jonathan R. MD; Busuttil, Ronald W. MD, PhD

doi: 10.1097/SLA.0b013e318148c704
Original Articles

Objective: To assess the efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) and the impact of current staging criteria on long term survival.

Summary Background Data: HCC is becoming an increasingly common indication for OLT. Medicare approves OLT only for HCCs meeting the Milan criteria, thus limiting OLT for an expanding pool of potential liver recipients. We analyzed our experience with OLT for HCC to determine if expansion of criteria for OLT for HCC is warranted.

Methods: All patients undergoing OLT for HCC from 1984 to 2006 were evaluated. Outcomes were compared for patients who met Milan criteria (single tumor ≤5 cm, maximum of 3 total tumors with none >3 cm), University of California, San Francisco (UCSF) criteria (single tumor <6.5 cm, maximum of 3 total tumors with none >4.5 cm, and cumulative tumor size <8 cm), or exceeded UCSF criteria.

Results: A total of 467 transplants were performed for HCC. At mean follow up of 6.6 ± 0.9 years, recurrence rate was 21.2%, and overall 1, 3, and 5-year survival was 82%, 65%, and 52%, respectively. Patients meeting Milan criteria had similar 5-year post-transplant survival to patients meeting UCSF criteria by preoperative imaging (79% vs. 64%; P = 0.061) and explant pathology (86% vs. 71%; P = 0.057). Survival for patients with tumors beyond UCSF criteria was significantly lower and was below 50% at 5 years. Multivariate analysis showed that tumor number (P < 0.001), lymphovascular invasion (P < 0.001), and poor differentiation (P = 0.002) independently predicted poor survival.

Conclusions: This largest single institution experience with OLT for HCC demonstrates prolonged survival after liver transplantation for tumors beyond Milan criteria but within UCSF criteria, both when classified by preoperative imaging and by explant pathology. Measured expansion of OLT criteria is justified for tumors not exceeding the UCSF criteria.

We analyzed the outcomes of 467 patients who underwent orthotopic liver transplantation for hepatocellular carcinoma over a 22-year period at our center. Patients with tumors meeting the Milan and University of California, San Francisco, criteria had >50% overall and recurrence-free survival rates at 5 years, whereas patients with tumors beyond University of California, San Francisco criteria fared much worse. On multivariate analysis, tumor number, lymphovascular invasion, and poor differentiation were independent predictors of survival.

From the Dumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

The project did receive grant support from The George T. Pfleger Foundation, The DuMont Foundation, The JoAnn Barr Foundation, Dr. Soliman Fakeeh, The W.K. Day Foundation, and Mr. Gilbert I. Garfield.

Reprints: Ronald W. Busuttil, MD, PhD, Room 72-160 CHS, UCLA Medical Center, 650 C.E. Young Drive, South, Box 956904, 72-160 CHS, Los Angeles, CA 90095-6904. E-mail:

© 2007 Lippincott Williams & Wilkins, Inc.