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Recurrent HCV infection after liver transplantation is universal and sustained clearance of HCV-RNA rarely occurs. The aim of this study was to characterize cell-mediated immunity and cytokine production in HCV-infected patients after liver transplant. The study included 6 pretransplantation patients (PT) and 15 liver transplanted patients, including 5 with spontaneous HCV-RNA clearance (SC group), 5 with sustained virological response after antiviral treatment (SVR group), and 5 no response (NR group). The control group included 5 HCV-RNA negative, anti-HCV negative healthy individuals. This study examines proliferative T-cell response and cytokine production (gamma-interferon and IL-10) after HCV specific and phytohemagglutinin (PHA) stimulation in cultured peripheral blood mononuclear cells (PBMCs) from each group. Multispecific proliferative responses to HCV antigens (mean Stimulation Index; SI) were higher in the SVR group (mean SI 7.4 +/- 2) and SC group, as compared with the NR group (P <.05, vs SVR) and PT group (P <.05, vs SVR and SC). After PHA stimulation, gamma-interferon levels were similar to controls (4330 +/- 640 pg/ml) in the SC (4474 +/- 300 pg/mL) and SVR groups (3647 +/- 300 pg/mL), but were significantly lower than controls in the PT (401 +/- 331 pg/mL; P <.02) and NR groups (546 +/- 360 pg/mL; P <.01). IL-10 production after PHA stimulation was similar in SC, SVR, and controls (647 +/- 279 pg/mL, 674 +/- 310 pg/mL and 841 +/- 294 pg/mL, respectively), but was lower in PT patients (232 +/- 94 pg/mL). The NR group showed high basal IL-10 production with little increase after stimulation. In conclusion, liver post-transplantation patients with spontaneous clearance of HCV-RNA and those with sustained viral response after therapy showed an immune response despite immunosuppression that might have contributed to their favorable outcome.

Orthotopic liver retransplantation (re-OLT) is highly controversial. The objectives of this study were to determine the validity of a recently developed United Network for Organ Sharing (UNOS) multivariate model using an independent cohort of patients undergoing re-OLT outside the United States, to determine whether incorporation of other variables that were incomplete in the UNOS registry would provide additional prognostic information, to develop new models combining data sets from both cohorts, and to evaluate the validity of the model for end-stage liver disease (MELD) in patients undergoing re-OLT. Two hundred eighty-one adult patients undergoing re-OLT (between 1986 and 1999) at 6 foreign transplant centers comprised the validation cohort. We found good agreement between actual survival and predicted survival in the validation cohort; 1-year patient survival rates in the low-, intermediate-, and high-risk groups (as assigned by the original UNOS model) were 72%, 68%, and 36%, respectively (P <.0001). In the patients for whom the international normalized ratio (INR) of prothrombin time was available, MELD correlated with outcome following re-OLT; the median MELD scores for patients surviving at least 90 days compared with those dying within 90 days were 20.75 versus 25.9, respectively (P =.004). Utilizing both patient cohorts (n = 979), a new model, based on recipient age, total serum bilirubin, creatinine, and interval to re-OLT, was constructed (whole model chi(2) = 105, P <.0001). Using the c-statistic with 30-day, 90-day, 1-year, and 3-year mortality as the end points, the area under the receiver operating characteristic (ROC) curves for 4 different models were compared. In conclusion, prospective validation and use of these models as adjuncts to clinical decision making in the management of patients being considered for re-OLT are warranted.

Cumulative recurrence after surgical resection for hepatocellular carcinoma (HCC) is very high. Several retrospective analyses have shown that liver transplantation was more effective than resection for patients with HCC at early tumor stages. Consequently, in January 1990, we decided to prospectively indicate orthotopic liver transplantation (OLT) as the first surgical treatment for small, localized HCC in cirrhotic patients without nodal involvement independently of the degree of liver function. The aim of this prospective cohort study was to analyze prognosis, recurrence rate, and survival after liver transplantation in patients in whom the main indication was HCC with cirrhosis. Thirty-eight patients in whom the main indication for liver transplantation was HCC and hepatic cirrhosis were compared with 136 transplantations because of cirrhosis without tumor, performed in our unit from January 1990 to December 1995. HCC arising in noncirrhotic livers and those incidently discovered after OLT were excluded from the study. Chemoembolization using doxorubicin, lipiodol, and Gelfoam was performed before OLT in 31 patients with good liver function. There were no differences in gender, but HCC patients were older (57 +/- 7 vs. 50 +/- 10 years [P < .001]). Liver function was better in HCC (Child-Pugh score: 6.9 +/- 2 vs. 8.6 +/- 1.8; P < .001), and hepatitis C virus antibody was positive in 31 (82%) vs. 51 (37%) (P < .007). Seven tumors had bilobar involvement (18%). Capsule was present in 22 (58%). The mean size of the tumor was 3.4 +/- 2 cm. Seventeen tumors (45%) were larger than 3 cm, and 4 (11%) were larger than 5 cm. The average number of nodules was 2 +/- 1. The tumor-node-metastasis stage of the tumors was pT1 in 6 patients (16%), 11 were pT2 (29%), 12 were pT3 (31%), and 9 were pT4 (24%). Seven patients were retransplanted in the HCC group (18%) and 19 (14%) in the nontumor group (not significant). Tumor recurrence was detected in three patients (8%). One, 3-, and 5-year survival rates were 82% vs. 79%, 75% vs. 71%, and 63% vs. 68%, respectively, for patients with and without HCC, and no differences were found between the two groups (P = .84). Survival was significantly reduced in patients with a macroscopic vascular invasion and tumors greater than 5 cm in diameter. Recurrence and mortality after liver transplantation in cirrhotic patients with carefully selected HCC are similar to the results in cirrhotic patients without tumor.