Liver transplantation for hepatocellular carcinoma

Abstract

Objective: To analyze patient and tumor characteristics that influence patient survival to select patients who would most benefit from liver transplantation.

Summary background data: The selection of patients with hepatocellular carcinoma (HCC) for liver transplantation remains controversial.

Methods: One hundred twelve patients with nonfibrolamellar HCC who underwent a liver transplant from 1985 to 2000 were reviewed. Survival was calculated using the Kaplan-Meier method, with differences in outcome assessed using the log-rank procedure. Multivariate analysis was then performed using a Cox regression model.

Results: Overall patient survival rates were 78%, 63%, and 57% at 1, 3, and 5 years, respectively. Patients infected with the hepatitis B virus had a worse 5-year survival than those who were not (43% vs. 64%), with most deaths being attributed to recurrent hepatitis B. However, patients with hepatitis B virus who underwent more recent transplants using antiviral therapy fared as well as those who were negative for the virus, showing a 5-year survival rate of 77%. Patients with vascular invasion by tumor had a worse 5-year survival than patients without vascular invasion (33% vs. 68%). Vascular invasion, tumor size greater than 5 cm, and poorly differentiated tumor grade were predictors of tumor recurrence by univariate analysis; however, only vascular invasion remained significant on multivariate analysis: the rate of tumor recurrence at 5 years was 65% in patients with vascular invasion and only 4% for patients without vascular invasion.

Conclusions: For well-selected patients with HCC, liver transplantation in the current era can achieve equivalent results to transplantation for nonmalignant indications. Vascular invasion is an indicator of high risk of tumor recurrence but is difficult to detect before transplantation.

Figure 1. Survival curve of 112 patients undergoing liver transplantation for hepatocellular carcinoma (HCC). The 5-year survival rate was 57%, not significantly different from patients receiving transplants for nonmalignant indications.

Figure 2. Causes of death were equally divided between recurrent tumor (HCC), recurrent liver disease, and other causes. Deaths resulting from other causes were mainly due to perioperative complications; recurrent liver disease was mainly viral with an intermediate course, whereas recurrent tumor was largely a later cause of death.

Figure 3. There was no difference in survival between patients found to have incidental tumors and those who had tumors identified before transplantation.

Figure 4. Transplant recipients who had hepatitis B (HBV +VE) had a worse outcome than those without hepatitis B (HBV -VE); however, this group of patients included patients undergoing transplantation before 1991, who received no antiviral prophylaxis.

Figure 5. Transplant recipients with hepatitis B who received antiviral prophylaxis (Hep B Rx) had an improved 5-year survival rate of 72%, with outcomes at least as good as recipients without hepatitis B.

Figure 6. There was no significant difference in outcome by tumor stage between stages I, II, and III, but patients with stage IV tumors fared poorly.

Figure 7. Patients with microscopic or macroscopic vascular invasion by tumor had a significantly worse survival than those without vascular invasion.

Figure 8. (A) Patients with vascular invasion had an actuarial tumor recurrence rate of 65%; the rate in those without vascular invasion was only 4%. (B) Patients with tumors larger than 5 cm were more likely to have tumor recurrence than those with smaller tumors. (C) Poorly differentiated grade was predictive of tumor recurrence, although relatively few patients had poorly differentiated tumors.