4 Selection of calcineurin inhibitor affects the rate of recurrence of primary biliary cirrhosis (PBC)

HEPATOLOGY, Vol. 38, No. 4, Suppl. 1, 2003

AASLD ABSTRACTS

3 THE IMPACT OF EXPANSION OF CONVENTIONAL TUMOR CRITERIA AND PRE-OPERATIVE LOCO-REGIONAL TREATMENTS ON SURVIVAL FOLLOWING LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA: RESULTS FROM TWO CENTERS. Francis Y

Yao, University of California San Francisco, San Francisco, CA; Milan Kinkhabwala, New York Presbyterian Hospital, New York, NY; Jeanne LaBerge, Nathan M Bass, Robert Kerlan, John P Roberts, University of California San Francisco, San Francisco, CA BACKGROUND: It has b e e n suggested that modest expansion of the conventional criteria used for orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) does not adversely impact survival. In this study, we further evaluated the outcome of OLT according to HCC stage, and reassessed the impact of the expanded criteria based on a combined analysis from two transplant centers. We also hypothesized that pre-operative transarterial chemoembolization (TACE) or ablation therapies might have played a role in preserving excellent survival after modest expansion of the tumor size limits. PATIENTS AND METHODS: The study cohort included 168 consecutive patients with HCC who underwent OLT from two liver transplant centers with at least 6 months of follow-up. Forty-four patients (26.2%) had incidental HCC. Seventy-six patients (45.2%) received pre-operative TACE alone, including 59 patients who received TACE within 24 hours prior to OLT w h e n a donor became available. Thirteen patients (7.7%) received ablation only, and 14 others (8.3%) received a combination of these treatments. Sixty-five patients (38.7%) received no specific pre-operative treatment. Pathologic tumor staging of the explanted liver revealed pT1 (single tumor under 2 cm) in 27 patients, pT2 (solitary tumor 2 to 5 cm; or 2 to 3 lesions none > 3 cm) in 90 patients, pT3 (1 nodule > 5.0 cm; 2 or 3 nodules, at least one > 3.0 cm) in 36 patients and pT4 (4 or more nodules of any size or gross invasion of the main portal vein) in 15 patients. The 24 patients (14.3%) with pT3 HCC who met the proposed expanded criteria (single lesion not exceeding 6.5 cm, or up to 3 lesions none greater than 4.5 cm with total tumor diameter up to 8 cm) were classified as pT3A. The other 12 patients with pT3 were assigned pT3B. RESULTS: Eighteen patients (10.7%) had HCC recurrence after a median of 243 days after OLT (range 32 to 976 days). The 5-year recurrence-free survival rates for patients with pT1, pT2, or pT3A were 100%, 93.8%, and 88.5%, respectively. The differences between the three groups were not statistically significant (p-0.61 by log-rank test between pT2 and pT3A). The recurrence-free survival was significantly reduced for patients with pT3B (59.3% at 5 years, p-0.006 versus pT2) and for pT4 (27.8% at 3 years, p<0.0001 versus pT2). The strongest predictor for HCC recurrence in the univariate Cox Proportional Hazards model was HCC stage exceeding the proposed T3A criteria (hazard ratio (HR) 15.4, p<0.0001). Other significant predictors for recurrence included microvascular invasion (HR 5.8, p-0.0003), poorly differentiated grade (HR 15.0, p-0.006), alpha-fetoprotein > 500 ng/ml (HR 4.7, P-0.003) and diagnosis of liver disease other than hepatitis C, hepatitis B or alcoholic liver disease (HR 3.1, P-0.04). The analysis of the impact of pre-operative TACE or ablation treatments was stratified according to HCC stage. In the subgroup of pT2 and pT3 combined at intermediate risk for HCC recurrence, the I and 5 year- recurrence-free survival rates were 96.4% and 93.8%, respectively, for the 85 patients who received pre-operative treatments, versus 91.5% and 80.6%, respectively, for the 41 patients who did not received pre-operative treatment (p-0.049 by log-rank test). The positive effect of pre-operative treatments appeared to be greater for the pT3 group (p-0.05) than the pT2 group (p-0.12). Treatment was associated with worse outcome in

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the pT4 group (p-0.02). CONCLUSION: Our results continued to support modest expansion of the tumor size limits based on a larger cohort of patients. Pre-operative TACE or ablation may benefit a subgroup of patients with HCC at intermediate risk for recurrence after OLT, and possibly play a role in preserving excellent survival after modest expansion of the tumor size limits. Disclosures: Nathan M Bass - No relationships to disclose Robert Kerlan - No relationships to disclose Milan Kinkhabwala - No relationships to disclose Jeanne LaBerge - No relationships to disclose John P Roberts - No relationships to disclose Francis Y Yao - No relationships to disclose

4

THE SELECTION OF CALCINEURIN INHIBITOR AFFECTS THE RATE OF RECURRENCE OF PRIMARY BILIARY CIRRHOSIS (PBC). James Neuberger, Bridget K Gunson, Queen

lizabeth Hospital, Birmingham, UK; Stefan G Hubscher, University of Birmingham Medical School Birmingham, UK; Peter Nightingale, Queen ~ lizabeth Hospital Birmingham, UK Introduction: it is now generally accepted that PBC recurs after liver transplantation although the effect on graft survival, at least in the medium term, is small. Identification of factors that are associated with disease recurrence may help in the understanding of the pathogenesis of the disease and may allow a tailored approach to post-transplant management. ethods: all patients grafted for PBC in this unit between 1982 and 2002 were evaluated. Post transplant, patients were maintained on immunosuppression with a calcineurin inhibitor (cyclosporine A (CyA) or tacrolimus (Tac)); azathioprine and corticosteroids. Steroids were withdrawn at 3 months. Patients underwent protocol liver biopsies at I year and initially at annual intervals and, after 1993, at 3 yearly intervals. The diagnosis of recurrent PBC was made on histologic criteria, including the presence of portal granulomas, inflammatory bile duct lesions and bile duct loss, in the absence of other causes of bile duct damage. To analyse risk factors associated with disease recurrence, both donor and recipient factors were analysed in a univariate and multivariate model. Findings: 485 patients were grafted for PBC: at transplant, the median age was 55 years and median serum bilirubin 151umol/L. The median follow-up time was 79 months. Overall, recurrence was first diagnosed in about 20% at 5 years and in 35% at 10 years. On univariate analysis, immunosuppression was associated with disease recurrence: use of azathioprine beyond one year and type of calcineurin inhibitor (CyA or Tac) were both associated with recurrence. No other recipient or donor factor was associated with recurrence. The median time to recurrence was 93 months if not taking azathioprine beyond one year and 120 months if taking azathioprine after I year (p-0.03)). However on multivariate analysis only immunosuppression with either CyA or Tac was significantly associated with recurrence (median time to recurrence 123 months for CyA and 62 months for tacrolimus, p<0.001). This difference was not an effect of the year of transplant or the number or timing of biopsies. Conclusions: The only factor identified that was associated with PBC recurrence was the type of immunosuppression. This should be considered w h e n tailoring immunosuppression to the individual patient Disclosures: Bridget K Gunson - No relationships to disclose Stefan G Hubscher - No relationships to disclose James Neuberger - No relationships to disclose Peter Nightingale - No relationships to disclose