Luis Casais

Efficacy of interferon for chronic hepatitis C virus–related hepatitis in kidney transplant candidates on hemodialysis: results after transplantation

OBJECTIVES:Interferon-α (IFN) may have undesirable effects on a functioning graft. The aim of this study was to evaluate IFN treatment in kidney transplant candidates during the hemodialysis period as well as the results after transplantation.METHODS:A total of 29 noncirrhotic hemodialysis patients with chronic hepatitis C virus (HCV) infection (based on long-term rise in ALT, HCV serology, HCV RNA by polymerase chain reaction methods, and histological evidence) were included. Tolerability to IFN treatment, pre- and posttransplantation therapeutic results, and long-term outcome were recorded. IFN regimen consisted of 3 million units (MU) times per week after hemodialysis sessions for 6 months, followed by 1.5 MU after each hemodialysis session for an additional 6 months. All patients gave informed consent for participation.RESULTS:IFN therapy was fairly well tolerated. Adverse effects due to IFN toxicity, renal disease, or causes related to the immunological properties of IFN were observed in 24% of patients. At the end of treatment, ALT had normalized in 23/28 patients (82.1%), and HCV RNA had cleared in 23/28 patients (82.1%). During follow-up, HCV RNA was persistently negative in 18 patients (64%, including transplant recipients). A total of 14 patients (nine HCV RNA–negative) received a kidney transplant. Mean follow-up after the procedure was 41 ± 28 months. In all, 12 patients had a functioning graft, one had acute vascular rejection, and one died of carcinoma. All transplanted patients maintained normal ALT levels, and eight remained HCV RNA–negative.CONCLUSIONS:Treatment results in our study population were better than those observed in the general population. The long-term response achieved, which was maintained after transplantation, supports the use of IFN for HCV hepatitis in kidney transplant candidates under hemodialysis.

Análisis de 500 trasplantes hepáticos en el Hospital de Bellvitge

Fundamento Se presenta la experiencia del programa de trasplante hepatico del Hospital de Bellvitge en 500 trasplantes realizados durante 15 anos, con el objetivo de poner de manifiesto los cambios que se han producido y exponer los resultados a largo plazo de esta terapeutica. Pacientes y metodo Se consideraron y compararon 5 grupos de 100 trasplantes consecutivos (I-V). Resultados Las indicaciones mas frecuentes fueron el hepatocarcinoma (23%), la cirrosis alcoholica (22,8%) y la hepatopatia cronica por virus C (18,8%). En 59 pacientes se llevaron a cabo 65 retrasplantes (13%), cuyas indicaciones mas frecuentes fueron la trombosis arterial (13 pacientes) y el fallo primario del injerto (10 pacientes). En 19 enfermos se realizo un trasplante combinado hepatorrenal. La causa mas frecuente de muerte del donante en el grupo I fueron los traumatismos craneales (80%), mientras que en el grupo V fue la enfermedad vascular (52%). Otras diferencias significativas entre estos grupos se observan en la proporcion de pacientes en estadio 2 y 3 de la clasificacion UNOS (el 45 frente al 19%), en el consumo de hemoderivados (29,6 [26] frente a 4,6 [5,3] concentrados de hematies), en la frecuencia de reintervenciones por hemoperitoneo (el 22 frente al 5%), en la estancia en UCI (13 [13] frente a 7,4 [11] dias) y en el hospital 40 [52] frente a 23,7 [17] dias), y en la incidencia de rechazo (el 46 frente al 20%) y de fallo primario del injerto (el 9 frente al 3%). Sin embargo, la prevalencia de infeccion (el 48 frente al 54,5%) y la incidencia de complicaciones biliares (el 26 frente al 20%) no han presentado variaciones significativas. La supervivencia actuarial de los pacientes trasplantados desde 1990 es del 83 y del 70% al ano y a los 5 anos, respectivamente. Conclusiones Se observa una mejoria notable y progresiva de los resultados del trasplante hepatico. Sin embargo, los tumores de novo, la recidiva de la hepatitis por virus C y el rechazo cronico pueden limitar los resultados a largo plazo.

Long‐term immune response after liver transplantation in patients with spontaneous or post‐treatment HCV‐RNA clearance

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. (Liver Transpl 2004;10:584–594.)

Successful treatment with tenofovir in a child C cirrhotic patient with lamivudine-resistant hepatitis B virus awaiting liver transplantation. Post-transplant results.

Antiviral treatment can be complex in decompensated hepatitis B virus (HBV) cirrhosis because of potential emergence of lamivudine‐resistant mutants and worsening liver function, and to multifactorial nephrotoxicity. Negative HBV‐DNA status by hybridization before liver transplantation is a favorable prognostic factor. We present the case of a 54‐year‐old HBV+ liver transplantation candidate who, after testing negative for HBV‐DNA, developed YMDD lamivudine‐resistant mutants resulting in a deteriorated clinical condition. After 8 months of adefovir plus lamivudine double therapy, only partial response was achieved. Tenofovir was added to this regimen, and an early decline of HBV‐DNA was seen at 4 weeks without adverse events. The patient underwent transplantation. At 21‐month postoperative follow‐up, the patients outcome was excellent. Post‐transplantation HBV prophylaxis, taking into account the prior development of mutants, consists of hepatitis B immunoglobulin plus lamivudine and adefovir. Tenofovir was well tolerated and produced a fast antiviral response, suggesting its potential value in combined antiviral treatment for liver transplantation candidates.

Resultados a largo plazo del tratamiento quirúrgico del hepatocarcinoma

Fundamento El tratamiento quirurgico del hepatocarcinoma (HCC) sigue siendo un tema controvertidopor falta de estudios prospectivos aleatorizados. Pacientes y metodo Entre enero de 1990 y diciembre de 2000 se realizaron en nuestro centro121 trasplantes hepaticos (grupo I) y 52 hepatectomias (grupo II) por HCC. La indicacion deuna u otra tecnica dependio de las caracteristicas del paciente y del tumor. Resultados Los pacientes del grupo I presentaron un estadio tumoral mas avanzado, con mayorincidencia de bilobularidad (19 frente a un 4%; p = 0,015) y un mayor numero de nodulos(1,9 DE [2] frente a 1,2 [0,6]; p = 0,001), pero el tamano tumoral medio fue inferior (3 cm[1,5] frente a 4,2 cm [3,2]; p = 0,006). La mortalidad operatoria (4 frente a un 2%; p =0,66), y la supervivencia a los 5 y 10 anos (68 y 42% frente a 63 y 45%; p = 0,23) fueron similarespara los dos grupos. Sin embargo, la incidencia de recidiva a los 5 y 10 anos (10,6 y10,6% frente a 50 y 65,5%; p Conclusiones Con una buena seleccion de los pacientes, tanto el trasplante hepatico como lahepatectomia obtienen excelentes supervivencias a largo plazo en los pacientes con HCC, aunqueel primero permite un mejor control de la enfermedad tumoral. Las causas de mortalidadson diferentes para cada uno de los tratamientos. La prolongacion del tiempo en lista de esperade trasplante que se ha producido en los ultimos anos no ha originado un empeoramiento delos resultados de supervivencia.

Liver transplantation in hepatocellular carcinoma

The initial enthusiasm for orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) soon vanished as early recurrences appeared. OLT in HCC remains a controversial issue. We evaluated the efficacy of preoperative studies to select No-Mo patients and determined whether pT stage and histopathological grade (G) have a prognostic significance. A group of 25 patients, all previously thoroughly studied to rule out extrahepatic disease, underwent OLT for HCC. All patients were pNo after pathological study and none of the six patients who died in the postoperative period showed extrahepatic dissemination at necropsy (pMo). The recurrence rate was 43%. The 2 and 5 years actuarial survival was 62% and 43% respectively. The pT and G were not prognostic factors for long-term survival. We think that HCC is still a good indication for OLT because almost 50% of patients have good survival prospects.

«De Novo» Carcinoma after Liver Transplant (L.T.)

Patients who have received a L.T. have a higher risk of developing «de novo» neoplasia than the general population.

HCV Chronic Infection in HD (Hemodialysed) Candidates to KT (Kidney Transplant). Influence of Virus C Genotypes on Response to IFN Treatment

IFN is the most accepted treatment for HCV chronic infection in immunocompetent patients. But IFN is not without risk in transplanted patients, because possible deleterious effects on the graft.