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Factors determining outcome of liver transplantation for hepatocellular carcinoma associated with hepatitis C cirrhosis
Factors Determining Outcome of Liver Transplantation for Hepatocellular Carcinoma Associated With Hepatitis C Cirrhosis R.M. Ghobrial, M. Shimoda, D.G. Farmer, H. Yersiz, P. Chen, S. Dawson, F. Amersi, S. Han, L.I. Goldstein, P. Martin, and R.W. Busuttil
T
HE EFFICACY of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. In this study we examined the clinicopathologic characteristics that may influence the long-term outcome of OLT for HCC in HCV patients. METHODS From 1990 to 1999, 463 adult patients underwent OLT for endstage liver disease (ESLD) secondary to HCV. Seventy patients (15.2%) exhibited concomitant HCC. A retrospective review was performed to identify variables associated with long-term patient and recurrent-free survival in this group of patients. Hepatitis C was diagnosed pre-OLT by anti-HCV seropositivity and/or PCR for detection of HCV-RNA. Univariate and multivariate analyses considered the following variables: gender; pTNM stage; tumor size; number of nodules; vascular invasion; incidental tumors; adjuvant chemotherapy; preoperative chemoembolization; tumor marker; lobar distribution; and histologic grade. Maintenance immunosuppression regimens consisted of either triple cyclosporine (CsA)-based or dual tacrolimus-based immunosuppression. Survival analysis was performed using the Kaplan–Meier method and compared by the log-rank test. Multivariate analysis was used by stepwise Cox regression.
RESULTS
Twenty-two female and 45 male adult patients who received an OLT for HCV and HCC were included in the study. Mean recipient age was 59.6 ⫾ 9.0 (36.4 to 73.0) years. Median follow-up time was 33.3 (1.2 to 105.8) months. Twenty-four of 67 patients (36%) died during the follow-up period over 3 months. Eight of 24 (33%) died of recurrent tumor (3 because of recurrent HCV), whereas 13 patients died from causes that were unrelated to HCV or HCC (8 sepsis, 2 GVHD, 1 MOF, 1 tuberculosis, 1 cardiomyopathy). Overall survival for HCV patients that underwent OLT for HCC was significantly lower when compared with patients who underwent OLT for HCV alone (75%, 68%, and 52% vs 84%, 76%, and 74%, P ⬍ .001) at 1, 3, and 5 years, respectively. Overall survival of patients with stage I HCC was significantly better than in patients with stage II, III, and IV (P ⫽ .007, .019, and .034). Eleven of 67 patients (16.4%) experienced tumor recurrence. Sites of recurrence
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included the transplanted liver (5 patients), lungs (5 patients), and bone (1 patient). Univariate comparison demonstrated that stage I (vs stages II, III, and IV; P ⬍ .05) was a good prognostic indicator for overall patient survival. By multivariate analyses, adjuvant chemotherapy (P ⬍ .05), preoperative chemoembolization (P ⬍ .03), and pTNM stage I (P ⬍ .03) were associated with improved patient survival. A reduced rate of recurrence was present in patients with stage I tumor (P ⫽ .038), negative vascular invasion (P ⫽ .0001), incidental tumors (P ⫽ .039), unifocal tumors (P ⫽ .069), and tumors of ⬍3 cm (P ⫽ .06). DISCUSSION
One previous report showed good patient survival with OLT for ESLD in HCV patients, with a 5-year actuarial survival rate of 76%.1 Factors that influence the outcome of OLT in HCV and HCC patients are not well defined.2–5 This study has demonstrated that OLT can be performed in HCV patients with concomitant HCC with good results. Stage I HCC is associated with survival equivalent to HCV cases without HCC. Preoperative chemoembolization and adjuvant chemotherapy may improve patient survival and should be considered in all patients. Vascular invasion, advanced tumor stage, multifocal tumors, and tumors ⬎ 3 cm are associated with increased rates of recurrence. REFERENCES 1. Ghobrial RM, Farmer DG, Baqurizo A, et al: Ann Surg 229:824, 1999 2. Iwatsuki S, Starzl TE, Sheahan DG, et al: Ann Surg 214:221, 1991 3. Farmer DG, Rosove MH, Shaked A, et al: Ann Surg 219:236, 1994 4. Bismuth H, Majno PE, Adam R: Semin Liv Dis 19:311, 1999 5. Klintmalm GB: Ann Surg 228:479, 1998. From the Department of Surgery, Dumont–UCLA Liver Transplant Center, (R.M.G., M.S., D.G.F., H.Y., P.C., S.D., F.A., R.W.B.) and Department of Medicine, UCLA School of Medicine (S.H., L.I.G., P.M.), Los Angeles, California, USA. Address reprint requests to Dr Ronald Busuttil, UCLA School of Medicine, 10833 LeConte Avenue 77-132 CHS, Los Angeles, CA 90095.
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
1358
Transplantation Proceedings, 33, 1358 (2001)
T
HE EFFICACY of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. In this study we examined the clinicopathologic characteristics that may influence the long-term outcome of OLT for HCC in HCV patients. METHODS From 1990 to 1999, 463 adult patients underwent OLT for endstage liver disease (ESLD) secondary to HCV. Seventy patients (15.2%) exhibited concomitant HCC. A retrospective review was performed to identify variables associated with long-term patient and recurrent-free survival in this group of patients. Hepatitis C was diagnosed pre-OLT by anti-HCV seropositivity and/or PCR for detection of HCV-RNA. Univariate and multivariate analyses considered the following variables: gender; pTNM stage; tumor size; number of nodules; vascular invasion; incidental tumors; adjuvant chemotherapy; preoperative chemoembolization; tumor marker; lobar distribution; and histologic grade. Maintenance immunosuppression regimens consisted of either triple cyclosporine (CsA)-based or dual tacrolimus-based immunosuppression. Survival analysis was performed using the Kaplan–Meier method and compared by the log-rank test. Multivariate analysis was used by stepwise Cox regression.
RESULTS
Twenty-two female and 45 male adult patients who received an OLT for HCV and HCC were included in the study. Mean recipient age was 59.6 ⫾ 9.0 (36.4 to 73.0) years. Median follow-up time was 33.3 (1.2 to 105.8) months. Twenty-four of 67 patients (36%) died during the follow-up period over 3 months. Eight of 24 (33%) died of recurrent tumor (3 because of recurrent HCV), whereas 13 patients died from causes that were unrelated to HCV or HCC (8 sepsis, 2 GVHD, 1 MOF, 1 tuberculosis, 1 cardiomyopathy). Overall survival for HCV patients that underwent OLT for HCC was significantly lower when compared with patients who underwent OLT for HCV alone (75%, 68%, and 52% vs 84%, 76%, and 74%, P ⬍ .001) at 1, 3, and 5 years, respectively. Overall survival of patients with stage I HCC was significantly better than in patients with stage II, III, and IV (P ⫽ .007, .019, and .034). Eleven of 67 patients (16.4%) experienced tumor recurrence. Sites of recurrence
0041-1345/01/$–see front matter PII S0041-1345(00)02509-4
included the transplanted liver (5 patients), lungs (5 patients), and bone (1 patient). Univariate comparison demonstrated that stage I (vs stages II, III, and IV; P ⬍ .05) was a good prognostic indicator for overall patient survival. By multivariate analyses, adjuvant chemotherapy (P ⬍ .05), preoperative chemoembolization (P ⬍ .03), and pTNM stage I (P ⬍ .03) were associated with improved patient survival. A reduced rate of recurrence was present in patients with stage I tumor (P ⫽ .038), negative vascular invasion (P ⫽ .0001), incidental tumors (P ⫽ .039), unifocal tumors (P ⫽ .069), and tumors of ⬍3 cm (P ⫽ .06). DISCUSSION
One previous report showed good patient survival with OLT for ESLD in HCV patients, with a 5-year actuarial survival rate of 76%.1 Factors that influence the outcome of OLT in HCV and HCC patients are not well defined.2–5 This study has demonstrated that OLT can be performed in HCV patients with concomitant HCC with good results. Stage I HCC is associated with survival equivalent to HCV cases without HCC. Preoperative chemoembolization and adjuvant chemotherapy may improve patient survival and should be considered in all patients. Vascular invasion, advanced tumor stage, multifocal tumors, and tumors ⬎ 3 cm are associated with increased rates of recurrence. REFERENCES 1. Ghobrial RM, Farmer DG, Baqurizo A, et al: Ann Surg 229:824, 1999 2. Iwatsuki S, Starzl TE, Sheahan DG, et al: Ann Surg 214:221, 1991 3. Farmer DG, Rosove MH, Shaked A, et al: Ann Surg 219:236, 1994 4. Bismuth H, Majno PE, Adam R: Semin Liv Dis 19:311, 1999 5. Klintmalm GB: Ann Surg 228:479, 1998. From the Department of Surgery, Dumont–UCLA Liver Transplant Center, (R.M.G., M.S., D.G.F., H.Y., P.C., S.D., F.A., R.W.B.) and Department of Medicine, UCLA School of Medicine (S.H., L.I.G., P.M.), Los Angeles, California, USA. Address reprint requests to Dr Ronald Busuttil, UCLA School of Medicine, 10833 LeConte Avenue 77-132 CHS, Los Angeles, CA 90095.
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
1358
Transplantation Proceedings, 33, 1358 (2001)