Introduction 1 2 5 4 13 14 4 11 15 17 5 Patients and Methods n n n 18 After LT, patients were followed with Q3 monthly alpha-fetoprotein (AFP) and CT along with standard post-LT evaluation. Recurrences were defined as new nodules diagnosed by CT with confirmed biopsy in most cases. Overall survival (OS) was death as a result of any cause after LT. Patients were followed until death or study closure (arbitrarily denoted as October 1, 2004). Data was collected until May 1, 2005 to ensure at least 6 months of follow-up for all patients. χ 2 p Results Patient Characteristics 1 n n n Table 1 Pretransplant Demographics of 155 Patients with HCC Who Underwent LT Pretransplant Criteria N p Median age (range) 57 (28–70) 0.48 Sex  0.38  Male 123 (79%)   Female 32 (21%)  Cause of liver disease  0.10  HCV 79 (51%)   HBV 25 (16%)   Alcohol 34 (22%)   Cryptogenic 7 (4.5%)   Alpha-1 antitrypsin 6 (3.9%)   NASH 2 (1.3%)   PBC 2 (1.3%)  Pretransplant therapy  0.67  Ablation 36 (23%)   Resection 6 (3.9%)   TACE 1 (0.6%)   EBRT 1 (0.6%)   None 111 (72%)  p NASH = nonalcoholic steatohepatitis, PBC = primary biliary cirrhosis, EBRT = external beam radiation therapy Histopathological Analysis 2 Table 2 Pathologic Characteristics of 155 Liver Explants Characteristic N p HR (95% CI) No. of tumors     Median (range, cm) 2 (1–20) 0.23   <3 126 (81%)    >3 29 (19%)   Bilobar 32 (21%) 0.15  Size     Median (range; cm) 2.6 (.1–16) 0.04 0.47 (0.14,1.61)  <5 cm 145 (94%)    >5 cm 15 (10%)   Stage     I 31 (20%) 0.007 1.17 (0.39,3.50)  II 69 (44%)    III 26 (17%)    IV 29 (19%)   Positive lymph nodes 3 (2.0%) 0.31  a     Microscopic 33 (21%) 0.001 3.16 (0.92,10.93)  Macroscopic 6 (4%) <0.001 54.2 (11.03,266.4)  None 121 (78%) b c Grade     Well/mod 115 (74%) 0.36   Poor 13 (9%)   d 27 (17%)   Margins     Positive 2 (1%) 0.25   Negative 153 (99%)   Incidental tumor 34 (22%) 0.19  p a b c d p p Predictors of Recurrence and Survival 1 1 p Figure 1 (A) (B)  p p p p 2 n n 3 Figure 2 The effect of TNM stage on DFS after LT for HCC.  Figure 3 The effect of vascular invasion on recurrence-free survival after LT for HCC.  2 Discussion 8 9 14 15 19 20 14 20 22 4 9 10 14 4 8 8 14 11 15 17 11 3 14 23 24 4 8 11 15 23 25 26 13 5 12 13 13 15 20 27 There are several limitations to this study and therefore some of the results should be interpreted with caution. The need to standardize grading systems for HCC has long been recognized and would allow us to determine if tumor grade is indeed an important prognostic marker for recurrence and survival. Few tumors in this study were graded as poorly differentiated; moreover, in 27 patients, their grade was not determined. Results from histopathological analysis are often met with inherent biases from the pathologist and comprehensive evaluation of the whole liver explant may vary among pathologists and institutions. Finally, with very few tumors containing macroVI, strong conclusions about prognostic characteristics concerning macroVI cannot be made in this report. Whether microVI is a harbinger of macroVI or in some way correlated with a more aggressive form of HCC remains unclear. 20 28 31 32 In summary, LT for HCC can be performed with acceptable survival outcomes. A single tumor characteristic alone does not appear to determine prognosis or outcome. In the present study, macroVI alone was associated with very poor outcomes after LT. Extending criteria of LT for advanced HCC is possible only with better patient selection using improved pre-LT staging and identification of histopathological biological markers such as macroVI that would preclude LT.