Search

Purpose: Hepatitis C (HCV) is the most common liver disease in patients transplanted with hepatocellular carcinoma (HCC) in the West. We examined predictors of HCC recurrence in liver transplant recipients with HCV., Methods: From 1997 to 2006, 53 patients with HCC and HCV underwent liver transplantation. Pre-and post-operative data (including liver biopsies 4 months post-transplant) were collected. Differences between HCC recurrence and non-recurrence groups were detected by Student's t test or chi-square test. Data were analyzed as predictors of HCC recurrence by logistic regression multivariate analysis. Cumulative survival was analyzed by Kaplan-Meier curves and compared by the log-rank test., Results: Eleven of 53 patients (20.8%) developed HCC recurrence at a median interval of 15 months (2 to 55 months). Median Histology Activity Index (HAI) of liver biopsies, AST, and ALT at 4 months were significantly greater in patients with HCC recurrence. Independent predictors of HCC recurrence were HAI ≥ 4 at 4 months, ALT ≥ 100 at 4 months, and vascular invasion. Patients with HCC recurrence had significantly decreased survival., Conclusions: In this preliminary study, Histology Activity Index and ALT at 4 months, as well as vascular invasion, predicted HCC recurrence in liver transplant recipients with HCV.

Current liver allocation policy in the United States grants liver transplant candidates with stage T2 hepatocellular carcinoma (HCC) a priority Model for End-Stage Liver Disease (MELD) score of 22, regardless of age. Because advanced age may portend an increase in all-cause mortality after transplantation for any diagnosis, the aim of this study was to examine overall posttransplant survival in elderly patients with HCC versus younger cohorts. Based on Organ Procurement and Transplantation Network data, Kaplan-Meier 5-year survival rates were compared. Recipients undergoing primary liver transplantation were stratified into cohorts based on age (<70 or ≥ 70 years) and the receipt of MELD exception points for HCC. Log-rank and Wilcoxon tests were used for statistical comparisons. In 2009, 143 transplants were performed for patients who were 70 years old or older. Forty-two percent of these patients received a MELD exception for HCC. Regardless of the diagnosis, the overall survival rate was significantly attenuated for the septuagenarians versus the younger cohort. After 5 years of follow-up, this disparity exceeded 10% to 15% depending on the populations being compared. The 1-, 2-, 3-, 4-, and 5-year actuarial survival rates were 88.4%, 83.2%, 79.6%, 76.1%, and 72.7%, respectively, for the patients who were younger than 70 years and 81.1%, 73.8%, 67.1%, 61.9%, and 55.2%, respectively, for the patients who were 70 years old or older. Five-year survival was negatively affected for patients with HCC who were younger than 70 years; this disparity was not observed for patients with HCC who were 70 years old or older. In conclusion, although patients who are 70 years old or older compose a small fraction of transplant recipients in the United States, patients in this group undergoing transplantation for HCC form an even smaller subset. Overall, transplantation in this age group yields outcomes inferior to those for younger cohorts. However, unlike patients who are less than 70 years old and receive MELD exception points, overall liver transplant survival is not affected by HCC at an advanced age., (Copyright © 2012 American Association for the Study of Liver Diseases.)

We present a case of a 10-month-old boy with BA who developed HCC and was treated with liver transplantation. A four-month-old boy was referred to our institution because of persistent jaundice, hepatomegaly, and coagulopathy. He had been treated for the diagnosis of neonatal hepatitis at an outside hospital. He was evaluated and was accepted as a liver transplant candidate, and was subsequently transplanted with a deceased donor liver allograft at the age of 10 months. His native liver showed established cirrhosis because of BA with one focus of moderately differentiated HCC, measuring 0.7 cm in a diameter with microscopic vascular invasion in pathological study. The postoperative course was uneventful, and he is well without recurrence four months after liver transplantation. The occurrence of HCC in a child under one yr old is extremely rare, and only three cases are reported so far including our case.

Purpose: 17-(demethoxy), 17-allylamino geldanamycin (17-AAG) suppresses growth in some cancers by inhibiting Heat shock protein 90 (Hsp90). We examined the effects of 17-AAG-mediated Hsp90 inhibition on human hepatocellular carcinoma (HCC) growth in vitro and in vivo., Methods: Human HCC cell lines, Hep3B and HuH7, were exposed to 17-AAG and cell viabilities and apoptosis were determined. Cell cycle profiles were analyzed and the G(2)/M cell cycle checkpoint proteins cdc2 and cyclin B1 were examined. Studies were performed to determine whether 17-AAG-mediated cdc2 decrease was due to altered gene expression, transcription, or protein degradation. The effects of 17-AAG on Hep3B and HuH7 xenograft growth in athymic nude mice were also examined., Results: Hep3B and HuH7 treated with 17-AAG versus untreated controls showed decreased cell viability and increased apoptosis. Cells treated with 17-AAG also showed an increased fraction in G(2)/M phase and an associated decrease in cdc2 through protein degradation rather than through other mechanisms. Hsp90 inhibition by 17-AAG also decreased HCC xenograft growth in association with decreased cdc2 expression., Conclusions: 17-AAG-mediated inhibition of Hsp90 abrogates human HCC cell growth in vitro and in vivo through cdc2 decrease, which in turn induces G(2)/M cell cycle arrest and apoptosis. Hsp90 is a mediator of HCC growth and survival and its inhibition may serve as a potential treatment.

Management of hepatocellular carcinoma in the early cirrhotic remains controversial. The exact role of liver transplantation versus resection remains to be determined. The following short review attempts to present the evidence for the respective roles of liver transplantation versus liver resection in early stage HCC.

Background: Early recurrence (ER) (<1 year) after liver resection is one of the most important factors that impact the prognosis of patients with hepatocellular carcinoma (HCC). We sought to determine factors associated with ER of HCC and examine the outcomes thereafter., Study Design: From March 2001 to June 2003, 56 patients underwent hepatic resection for HCC at University of Toronto and were prospectively followed with median followup of 24 months. Patients with ER were compared with those who remained disease free for more than 1 year. Patient characteristics, tumor stage, and operative procedures were evaluated for their prognostic significance by univariate and multivariable analysis. Time to recurrence and time to death were analyzed using Kaplan-Meier survival curves and compared using log-rank analysis., Results: The initial procedure in all patients was surgical hepatectomy. ER occurred in 21 patients (38%), 31 (55%) remained disease free for more than 1 year, and 4 (7%) were omitted from evaluation because of early (<30 days) death. Median survival after initial hepatic resection for those with ER was 27 months, and 2-year survival was 54%. There were no deaths in the group that remained disease free for more than 1 year (100% 2-year survival, p < 0.05). By multivariate analysis, vascular invasion and positive microscopic margins were significant predictors when all 4 variables were considered in the model (p < 0.05). After ER, 11 of 21 patients (52%) underwent additional therapy with significant improvement in median survival (33 months) compared with those not eligible for conventional therapy (18 months, p = 0.05)., Conclusions: ER after liver resection for HCC is the leading cause of death during the first 2 years after potentially curative resection. ER will develop in approximately 75% of patients with either vascular invasion or positive margins. For patients with these predictive factors additional treatment might be advised.