The Silver Study: An Investigator-Initiated Trial to Determine if Sirolimus Use Can Improve HCC Recurrence-Free Survival in Affected Liver Transplant Recipients

Abstract

6 7 9 THURSDAY Supplement to Transplantation July 27, 2008, Volume 86 Number 2SHCC, and no mortality occurred during the follow-up (mean, 35 ± 8.5 months; range 26-45 months). In conclusion, the incidence of HCC in cirrhotic patients who underwent liver transplant is similar to that of other studies in literature. The incidentally found HCC showed less invasive pathological features and a better prognosis than preoperatively detected HCC. The recurrence of hepatocellular carcinoma (HCC) after transplantation is main limitation of liver transplantation. Therefore the several selection criteria for liver transplantation in HCC patients are established. The objective of this study was to verify the clinical validity of selection criteria by pretransplant radiologic imaging study. recipients (49 whole liver transplant and 20 partial liver transplant) were enrolled this study. We analyzed the posttransplant survival and recurrence rate by radiologic selection criteria and other clinical factors. Grouping by pre-transplant criteria for liver transplantation, 16 recipients (23.2%) were above Milan criteria and 7 recipients (10.1%) were above the UCSF (University of California, San Francisco) criteria. According to combined categories, nine recipients (13.0%) were grouped as above Milan/ below UCSF group. The recipients who met Milan criteria (below Milan) and UCSF criteria (below UCSF) showed 85.8% and 82.7% of 1-year survival rate respectively, which was comparable to that of non-HCC (91.6%) without signifi cance (p=0.767 in below Milan, p=0.2604 in below UCSF). During post-transplant followup period (1-52 months, 14.8 ± 12.0 months), 16 recurrences (23.2%) were diagnosed. There was a signifi cant difference in the 1-year recurrence-free survival rate according to the selection criteria, recipients who satisfi ed the Milan criteria was 78.6% and of those that did not meet these criteria was 22.7% (p<0.0001), with regard to the UCSF criteria, 72.0% and 14.2%, respectively (p<0.0001). According to combined grouping, 1-year recurrencefree survival rate was 25.4% in above Milan/below UCSF group. There was signifi cant difference among each groups (overall p<0.0001) (Figure) which was confi rmed in multivariate survival analysis. The application of the UCSF criteria by pre-transplant radiologic fi ndings as patient selection criteria for liver transplantation is limited.

Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation

“…Our data should be confirmed in a randomized prospective trial, and such a trial is currently beginning in Europe. However, this study is still in the enrollment phase, and there are no results published yet 31. Nonetheless, on the basis of our data, we can conclude that sirolimus is well tolerated at the studied doses as a treatment for patients transplanted for HCC, and it was not associated with toxicity beyond that from the systemic chemotherapy regimen.…”

Blood Transfusions and Tumor Biopsy May Increase HCC Recurrence Rates after Liver Transplantation

“…Between 2001 and 2006 sirolimus was used in some patients, mainly in those with more advanced tumor stages, based on meeting of the cost for off-label use by the responsible health insurance. Since 2006 a total of 57 HCC patients were enrolled in a prospective randomized multicenter trial primarily using sirolimus for long-term immunosuppression [12]. …”

Early γGT and bilirubin levels as biomarkers for regeneration and outcomes in damaged bile ducts after liver transplantation

“…Notably, survival in the cohort we analyzed in this study was exceptionally low due to the inclusion of a disproportionally high number of high‐risk cases. For example, we had patients from the SiLVER Study 27 in our cohort, which were high risk HCC patients. Also, introduction of the MELD system has resulted in survival rates in Germany below the international average, as published by Weismüller et al.…”