Liver transplantation results for hepatocellular carcinoma in Chile.
ABSTRACT 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.
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ABSTRACT: To see whether or not there is an association between the cause of cirrhosis and the number of hepatocellular carcinoma (HCC) nodules, we analyzed 178 consecutive patients in whom HCC was detected during a prospective screening by abdominal ultrasound (US). The relevant information was obtained from the database of the screening programs operating at four hospitals in the Milan area. One hundred twenty-nine (72%) patients had a single tumor nodule detected by US and 49 (28%) patients had multinodular disease. Ninety-eight (55%) patients had normal serum values of alpha-fetoprotein (AFP). Tumor staging with biphasic computed tomography (CT) scan or hepatic arteriography with lipiodol revealed that 101 (57%) patients had single tumor nodules and 77 (43%) patients had more than one HCC nodule. After staging, multinodular HCC was more common in patients with multiple risk factors than in the hepatitis C virus (HCV) carriers (56% vs. 38%, P =.05). Interestingly, single tumors were as common in the 126 patients undergoing 6-month interval screening as in the 52 patients who were studied at yearly intervals. The former patients, however, had more small tumors than the latter ones (91% vs. 74%, P =.04). The 22 patients who were alcohol abusers had normal levels of serum AFP more often than the hepatitis B virus (HBV) or HCV carriers or those with multiple risk factors (86% vs. 57%, P <.04; vs. 47%, P <.002; vs. 52%, P <.006, respectively). We concluded that multinodular HCC was underdetected by real time US; it prevailed among patients with multiple risk factors. In these patients, screening with US exams every 6 months may be inadequate for early detection of liver cancer.Hepatology 07/1999; 29(6):1704-7. · 12.00 Impact Factor
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ABSTRACT: The preferred therapy for hepatocellular carcinoma (HCC) apparently confined to the liver is surgical removal of the tumor. If the location of the tumor and the functional status of the liver are such that resection with an adequate margin can be achieved with low likelihood of subsequent hepatic failure, liver resection is the preferred approach. When HCC apparently localized to the liver is diagnosed in a patient who, by virtue of tumor characteristics or diminished hepatic reserve, is not a candidate for liver resection, liver transplantation becomes a consideration. This work outlines the approach at The Mount Sinai Hospital to the diagnosis, evaluation, preoperative management, transplantation, and posttransplant follow-up in patients with unresectable HCC. The allocation of livers to patients with HCC is reviewed, and predictors of tumor recurrence and results of liver transplantation for HCC are discussed. Finally, the impact of viral hepatitis and of immunosuppression on transplant outcome are discussed.Liver Transplantation 03/2004; 10(2 Suppl 1):S81-5. · 3.94 Impact Factor
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ABSTRACT: The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult. We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Thirty-three patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation, the patients were followed prospectively for a median of 26 months (range, 9 to 54). No anticancer treatment was given after transplantation. The overall mortality rate was 17 percent. After four years, the actuarial survival rate was 75 percent and the rate of recurrence-free survival was 83 percent. Hepatocellular carcinoma recurred in four patients (8 percent). The overall and recurrence-free survival rates at four years among the 35 patients (73 percent of the total) who met the predetermined criteria for the selection of small hepatocellular carcinomas at pathological review of small hepatocellular carcinomas at pathological review of the explanted liver wer 85 percent and 92 percent, respectively, whereas the rates in the 13 patients (27 percent) whose tumors exceeded these limits were 50 percent and 59 percent, respectively (P=0.01 for overall survival; P=0.002 for recurrence-free survival). In this group of 48 patients with early-stage tumors, tumor-node-metastasis status, the number of tumors, the serum alphafetoprotein concentration, treatment received before transplantation, and 10 other variables were not significantly correlated with survival. Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.New England Journal of Medicine 04/1996; 334(11):693-9. · 51.66 Impact Factor
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: email@example.com
© 2010 by Elsevier Inc. All rights reserved.
360 Park Avenue South, New York, NY 10010-1710
0041-1345/10/$–see front matter
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.
300GABRIELLI, VIVANCO, HEPP ET AL
nostic factor for survival.10,11In the present study, the mean
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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