Impact of Brazilian expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a multicenter study.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the main indications for orthotopic liver transplantation (OLT). In Brazil, selection criteria for HCC is an expanded version of the Milan Criteria (MC), the so-called "Brazilian Milan Criteria" (BMC). Our aims were to evaluate post-OLT outcomes in patients with HCC and analyze the BMC performance. MATERIALS AND METHODS: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,059 liver transplant recipients with HCC. Tumor was staged according to MC and BMC and correlated with overall survival (OS) and disease-free survival (DFS). We compared the ability of MC and BMC to predict OS and DFS using Delta C-statistic. RESULTS: Post-OLT OS were 63% in five years and HCC recurrence was observed in 8% of patients. At diagnosis, 85% of patients were within MC. Patients within MC at diagnosis and in the explant showed a higher OS and DFS than patients outside MC and within BMC and patients outside both criteria (p < 0.001). Patients outside MC in the explant had an increased risk of tumor recurrence (HR: 3.78; p < 0.001) and poor survival (HR:1.77; p = 0.003). The BMC presented a lower performance than MC in properly classifying patients regarding recurrence risk. CONCLUSIONS: In a large Brazilian cohort of HCC patients submitted to liver transplantation, we observed satisfactory overall survival and recurrence rates. However, patients transplanted within the Brazilian expanded criteria had lower OS and DFS when compared to patients within MC, which may generate future discussions regarding the criteria currently used.

Hepatocellular carcinoma recurrence after liver transplantation in a Brazilian multicenter study: clinical profile and prognostic factors of survival.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. PATIENTS AND METHODS: We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. RESULTS: OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. CONCLUSION: In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.

Hepatocellular carcinomas within the Milan criteria: predictors of histologic necrosis after drug-eluting beads transarterial chemoembolization.

PURPOSE: To evaluate pathologic, imaging, and technical predictors of therapy response in patients with hepatocellular carcinoma (HCC) within the Milan criteria undergoing doxorubicin drug-eluting beads transarterial chemoembolization (DEB-TACE) before orthotopic liver transplantation (OLT). METHODS: This prospective study included consecutive patients with HCC who underwent DEB-TACE before OLT. Tumor histologic necrosis on liver explants was utilized as the standard of reference to categorize treated HCCs as group 1 (>50 % necrosis) or group 2 (≤50 % necrosis). DEB-TACE technique, histological factors, and imaging evaluation utilizing the modified Response Evaluation Criteria in Solid Tumors (mRECIST) were compared between groups 1 and 2. RESULTS: Twenty-seven HCCs were identified in 23 patients. Group 1 comprised 18 HCCs (mean necrosis 86.2 %). Group 2 comprised 9 HCCs (mean necrosis 31.1 %). The mean time between the last DEB-TACE session and the OLT was 112 days. Lesion size was significantly larger in group 1 (mean 3.2 cm; 95 % confidence interval 2.55-3.85) than in group 2 (mean 2.1 cm; 95 % confidence interval 1.79-2.48) (p = 0.030). Group 1 also demonstrated a higher frequency of encapsulated lesions when compared to group 2 (78 % vs. 22 %; p = 0.0027). A significant linear correlation was found between the quantification of necrosis by imaging and pathology (p = 0.0011) using the mRECIST, with a poorer correlation index in group 2. CONCLUSION: Larger and encapsulated HCCS are associated with a higher percentage of necrosis. A significant linear correlation between the amount of necrosis by imaging and pathology was encountered when mRECIST was utilized.