Liver transplantation outcomes for early-stage hepatocellular carcinoma: Results of a multicenter study

Abstract

The incidence of hepatocellular carcinoma (HCC), a frequent and incurable complication of cirrhosis, continues to rise. Orthotopic liver transplantation (OLT) has been proposed as a treatment for unresectable, intrahepatic HCC limited in extent to the Milan criteria adopted by the United Network of Organ Sharing (UNOS) in 1998. More recently, somewhat less restrictive University of California, San Francisco (UCSF) 10 , criteria were proposed. To examine the long-term outcomes of OLT for HCC patients and to assess the UNOS policy of assigning weighted allocation points to patients with HCC, we retrospectively analyzed 144 patients (113 after 1998) with HCC who underwent OLT over an 11-year period at 3 institutions from UNOS Region 1. We compared their outcomes with 525 patients (272 after 1998) who underwent OLT for nonmalignant liver disease. The 1-and 5-year survival rates were 80.3% and 46.7%, respectively, for patients with HCC and 81.5% and 70.6%, respectively, for patients without HCC (P ‫؍‬ .020). However, there was no difference in survival between HCC and non-HCC patients after implementation of disease-specific allocation for HCC in 1998. A higher proportion of the HCC cohort was older and male and had chronic HCV infection and alcoholic liver disease. In univariate analysis, having alpha-fetoprotein (AFP) levels of 10 ng/mL or less and meeting clinical and pathologic UCSF criteria were each significant predictors of improved survival (P ‫؍‬ .005, P ‫؍‬ .02, and P ‫؍‬ .03, respectively). AFP greater than 10 ng/mL and exceeding pathologic UCSF criteria were also significant predictors of recurrence (P ‫؍‬ .003 and P ‫؍‬ .02, respectively). In conclusion, taken together, our data suggest that OLT is an acceptable option for patients with early HCC and that UCSF criteria predict outcome better than Milan or UNOS criteria. Regardless of which criteria are adopted to define eligibility, strict adherence to the criteria is important to achieve acceptable outcomes.

Milan criteria in liver transplantation for hepatocellular carcinoma: An evidence-based analysis of 15 years of experience

“…39,63,77 In agreement with the proven role of AFP as a prognostic tool (rather than a diagnostic tool) for HCC, high serum levels of AFP have been correlated with a deterioration in the prognosis of patients with tumors belonging to the MC category, even though a precise cutoff is missing (Table 3). Although the strength of the evidence is impoverished by the suboptimal quality (average NOS score ¼ 6) and the limited number of studies, 12,18,20,24,35,36,[38][39][40]51,54,65,80 AFP in clinical practice represents a quite reliable and noninvasive tool for capturing potentially more aggressive HCCs within the MC. In some centers, values > 400 or >1000 ng/mL are often important determinants for delisting patients otherwise eligible for LT. 24,119,120 4.…”

“…99 Indeed, in 9 studies, patients with chronic hepatitis and cirrhosis who met the MC and underwent LT for HCC achieved posttransplant survival rates comparable to those of patients with nontumor indications for LT. Although they were not designed to specifically address a survival equivalence between LT patients within the MC and LT patients with nontumor indications, 4 prospective cohort studies (level 1b) 2,10,11,13 and 5 retrospective cohort studies 29,32,39,45,46 (level 2b) reported 5-year survival rates of 65% to 78% for patients meeting the MC and 68% to 87% for patients with nontumor indications. The European Liver Transplant Registry, the Organ Procurement and Transplantation Network, and the Australian and New Zealand Liver Transplant Registry 100-102 have confirmed survival rates of 70% to 82% for patients with nontumor indications.…”

“…The meta-analysis included 19 studies 2,15,16,19,26,33,35,39,40,42,46,48,[53][54][55]57,63,67,84 that used different methodologies to compare the overall survival of patients meeting the MC and patients exceeding the criteria at the time of the explant pathology examination; 3949 patients were also stratified by the graft origin (deceased or living donors).…”

“…In this respect, the MC remain the benchmark for any other prognostic criteria proposed for expanding the use of LT in patients with cirrhosis and HCC. 24,40,80 or >1000 ng/mL 12,18,51 Up-to-7 criteria met 21,26 Tumor size >3 cm, 36 12,30,33 Total tumor volume >28 cm 3 35 or >115 cm 3 24 Total tumor diameter >8 cm 12,42 Bilobar nodules 66 Multiple nodules 52,71,76 Nodule number >3 25,26 and 13 level 2b studies 27,30,33,34,36,39,40,42,47,48,[51][52][53] have confirmed the likelihood of detecting mVI, grade 3 tumors, and microsatellites as the tumor size and number increase beyond the MC. In patients with HCCs meeting the MC, mVI is detected at a rate of 10% to 15%, poorly differentiated tumors are detected at a rate of 13% to 33%, and microsatellites are detected at a rate of 7% to 28%.…”

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

“…Factors associated with tumor recurrence include tumor burden and vascular invasion. 4,5,7,9,[11][12][13][14][15][16][17] Recurrence tends to occur in 6.4% to 21.2% of patients 8,9,11,12 ( Table 1). The 5-year patient survival rate after HCC recurrence is only 22%.…”