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Liver Transplantation for Advanced Hepatocellular Carcinoma Using Poor Tumor Differentiation on Biopsy as an Exclusion Criterion

DuBay, Derek MD; Sandroussi, Charbel MBBS, MMSc; Sandhu, Lakhbir MD; Cleary, Sean MD; Guba, Markus MD; Cattral, Mark S. MD; McGilvray, Ian MD, PhD; Ghanekar, Anand MD, PhD; Selzner, Markus MD; Greig, Paul D. MD; Grant, David R. MD

doi: 10.1097/SLA.0b013e31820508f1
Original Study

Background: Liberal acceptance criteria are used when offering liver transplantation (LTx) for treatment of hepatocellular carcinoma (HCC) at our center. This provides a unique opportunity to assess outcomes in a large North American series of patients with advanced tumors.

Objective: We hypothesized that acceptable survival rates can be achieved with LTx for any size or number of HCC provided that (a) imaging studies ruled out vascular invasion; (b) the HCC was confined to the liver; and (c) the HCC was not poorly differentiated on biopsy.

Methods: Survival, based on pretransplant imaging staging, was compared between 189 Milan Criteria (M) and 105 beyond Milan Criteria (M+) HCC patients who received an LTx between 1996 and 2008.

Results: Imaging understaged 30% of the M group and overstaged 23% of the M+ group. There was no difference in the 5-year overall survival in the M (72%) and M+ (70%) groups or 5-year disease-free survival in the M (70%) and M+ (66%) groups. The introduction of a protocol for a biopsy to exclude patients with poorly differentiated tumors and use of aggressive bridging therapy improved overall survival in the M+ group (P = 0.034). Serum alpha-fetoprotein more than 400 at LTx was associated with poorer disease-free survival (hazard ratio: 2.3; P = 0.031).

Conclusions: Cross-sectional imaging did not reliably stage patients with HCC for LTx. A protocol using a biopsy to exclude poorly differentiated tumors and aggressive bridging therapy achieved excellent survival rates with LTx for otherwise incurable advanced HCC, irrespective of tumor size and number.

We examined the survival of a large cohort of patients transplanted for advanced hepatocellular carcinoma. Macrovascular invasion was the only criteria used to exclude patients from transplantation; tumor number and size were not considered. The 5-year overall survival was excellent in both Milan (72%) and beyond Milan Criteria (70%) groups.

From the Liver Transplant Unit, Multiorgan Transplant Program, University of Toronto and Toronto General Hospital, University Health Network, 585 University Avenue, Toronto, Ontario, M5M 1G2, Canada.

Reprints: David Grant, MD, 11–1248NCSB, MultiOrgan Transplant Program, Toronto General Hospital, University Health Network, 585 University Ave, Toronto, Ontario, Canada. E-mail:

D.D. and C.S. contributed equally to first authorship.

© 2011 Lippincott Williams & Wilkins, Inc.