Liver Transplantation Results for Hepatocellular Carcinoma in Chile
M. Gabrielli, M. Vivanco, J. Hepp, J. Martínez, R. Pérez, J. Guerra, M. Arrese, E. Figueroa, A. Soza,
R. Yáñes, R. Humeres, H. Rios, J.M. Palacios, R. Zapata, E. Sanhueza, J. Contreras, G. Rencoret,
R. Rossi, and N. Jarufe
Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Liver
transplantation is the best treatment for HCC; it improves survival, cures cirrhosis, and
abolishes local recurrence. We describe the outcomes of patients with HCC who
underwent liver transplantation in two liver transplantation centers in Chile.
This study is a clinical series elaborated from the liver transplantation
database of Pontificia Universidad Católica and Clínica Alemana between 1993 and 2009.
The survival of patients was calculated using the Kaplan-Meier survival analysis. The
significant alpha level was defined as ?.05.
From 250 liver transplantations performed in this period, 29 were due to HCC.
At the end of the study, 25 patients (86%) were alive. The mean recurrence-free survival
was 30 months (range 5 months to 8 years). The 5-year survival for patients transplanted
for HCC was ?80%; however, the 5-year overall survival of patients who exceeded the
Milan criteria in the explants was 66%. There was no difference in overall survival between
patients transplanted for HCC versus other diagnosis (P ? .548).
This series confirmed that liver transplantation is a good treatment for
patients with HCC within the Milan criteria.
eighth in women.1Liver cirrhosis for hepatitis B and C as
well as alcohol, are the diseases most strongly associated
with HCC,2although recently obesity and diabetes have
emerged as risk factors.3
Curative treatments for HCC include liver resection and
liver transplantation. Radiofrequency ablation may also be
curative for small tumors. Other therapies, such as ethanol
injection, chemoembolization, and systemic chemotherapy,
have generally failed to show good results in terms of
survival.4In 1996, a pivotal report from the Milan center in
Italy,5showed a 4-year survival of 85% and a recurrence-
free survival of 92% for HCC patients with a single tumor
measuring ?5 cm in diameter or with no more than 3
tumors each not exceeding 3 cm and no proven vascular
invasion who were treated with liver transplantation. There-
fore, at present, liver transplantation (LT) is a good
treatment for HCC, improving survival, reducing local
recurrence rates, and abolishing the underlying cirrhotic
liver.6Our aim was to assess the overall survival outcomes
CC is the most common primary tumor of the liver. It
ranks fifth among all malignant tumors in men and
of patients with HCC treated with LT in two centers in
This clinical series from Pontificia Universidad Católica and Clínica
Alemana liver transplantation programs included databases elab-
orated between 1993 and 2009. We obtained demographic charac-
teristics from all patients. The diagnosis of HCC was performed
using two dynamic images, alpha-fetoprotein levels, or biopsy. The
examined follow-up was 4 years which was achieved in all patients.
Survival plots were estimated using the Kaplan Meier method for
HCC patients compared with non-HCC patients treated with LT.
The survival differences were tested for trends with log-rank tests.
From the Liver transplantation Program, School of Medicine,
Pontificia Universidad Católica de Chile (M.G., J.H., J.M., R.P.,
J.G., M.A., E.F., A.S., R.Y., N.J.), and the Liver transplantation
Program, School of Medicine, Clínica Alemana–Universidad del
Desarrollo (M.V., R.H., H.R., J.M.P., R.Z., E.S., J.C., G.R., R.R.),
Address reprint requests to Nicolás Jarufe Cassis, MD, Liver
Transplantation Program Pontificia Universidad Católica de Chile,
Santiago, Chile. E-mail: firstname.lastname@example.org
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Transplantation Proceedings, 42, 299–301 (2010) 299
The closing date for the survival analysis was august 31, 2009. The
SPSS program 15.0 for Windows was used for statistical analyses,
with a significant alpha level defined as ?.05.
In the study period 250 LT were performed, including 27
for HCC. The diagnosis was established preoperatively in
17 patients and by histologic examination of the explanted
liver in 12. Liver transplantation for HCC represented
11.6% of all cases; patients were predominantly men, ranging
in age from 15 to 71 years (Table 1).
When the diagnosis of HCC was confirmed before liver
transplantation surgery, 88% of patients (15) underwent
treatment. The 23 procedures performed on this group
most frequently included transarterial chemoembolization.
In 12 patients, multifocal lesions were detected. The me-
dian waiting time for surgery was 12 months (range 2–24).
Ten patients exceeded the Milan criteria upon anatomor-
phologic examination of the explanted liver.
At the end of the study, 25 patients transplanted for HCC
were alive, and four (13%) had tumor recurrences all of
whom exceeded the Milan criteria in their native explants.
The mean recurrence-free survival was 30 months (range 5
months to 8 years). The 5-year overall survival for all
patients transplanted for HCC was 86%, and for patients
who fulfilled the Milan criteria at explantation it was 94.7%.
The 5-year overall survival of patients who exceeded the
Milan criteria in their explants was 66%. Figure 1 shows the
overall survival for transplanted patients for all diagnoses
and Fig 2 for subjects subdivided by diagnosis. The overall
survival rates for hepatocellular carcinoma patients trans-
planted were similar between the centers (P ? .48).
This is the first Chilean cooperative clinical series of liver
transplantation for hepatocellular carcinoma. In this study,
there was no significant difference in survival between trans-
plant patients with versus without HCC. The ten patients
who exceeded the Milan criteria displayed shorter survival
than those who did not exceed them, but because of the
small sample sizes they did not significantly alter the overall
survival of HCC patients. In 1997, Figueras et al7reported
the results of a prospective study regarding liver transplan-
tation as the primary treatment for patients with small HCC
versus without HCC. They did not observe a significant
difference in survival between the groups.
The risk of HCC among patients with chronic hepatitis C
is high, namely 2%–8%.8In the present study, 44% of
patients with HCC bore hepatitis C virus; no patients with
hepatitis B virus had HCC. A Brazilian study9reported a
rate of 31.1% of HCC patients bearing hepatitis C virus and
13.3% bearing hepatitis B virus.
An important issue in liver transplantation for HCC is
the time a waiting a suitable graft. Some studies have
reported that waiting time represents an important prog-
diagnosis: hepatocellular carcinoma (HCC) versus other diagnosis.
Overall survival for transplanted patients according to
Table 1. Demographic Characteristics
HCC Other Diagnosis
Cause of liver disease
Hepatitis C virus (%)
Hepatitis B Virus (%)
Child-Pugh class n (%)
*P ? .05; **Not significant.
Overall survival for all transplanted patients.
300 GABRIELLI, VIVANCO, HEPP ET AL
nostic factor for survival.10,11In the present study, the mean Download full-text
waiting time was 12 months. Llovet et al12reported that
23% of waiting patients dropped out of the list during the
first 6 months owing to tumor progression. In Chile there is
a shortage of donors, so waiting times are prolonged,
exceeding the 6 months recommended for transplantation
in HCC. Therefore, most patients in the present series
underwent one or more pretransplant bridge therapies.
Liver transplantation is an effective option for HCC
patients meeting the Milan criteria. Several published
reports have shown 3-year disease-free survival rates of
70%.13,14In the present series, the 3-year survival for
patients transplanted for HCC was ?80%. Nevertheless,
one should consider that in a significant percentage of our
patients, the diagnosis of HCC was made as an incidental
finding in the explanted liver biopsy; liver damage was the
indication for the transplantation.
The time between the last imaging and transplantation
was ?6 months in some cases, because they were referred
from other centers where there were no resources for
frequent imaging tests. This fact may explain the high
number of cases who were outside the Milan criteria in this
series (34%). Although their survival was lower than that of
candidates meeting the Milan criteria, the 66% 5-year
survival rate remains significant.
In conclusion, this study yielded results consistent with
the available literature showing that liver transplantation is
the best therapy for HCC with remarkable long-term
survival among cases that meet the Milan criteria.
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