L. Castells

Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study.

Eighty‐four HCV/HIV‐coinfected and 252‐matched HCV‐monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty‐six (43%) HCV/HIV‐coinfected and 75 (30%) HCV‐monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42–64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420–3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV‐coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32–6.76), donor risk index (HR, 9.48; 95% CI, 2.75–32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03–0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV‐infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5‐year prognosis (69%[95% CI, 54–80]) to that of HCV‐monoinfected recipients. In conclusion, 5‐year survival in HCV/HIV‐coinfected liver recipients was lower than in HCV‐monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.

Predictive factors for early mortality following liver transplantation

Abstract: Aims: To retrospectively review our liver transplant performance to identify factors that influenced early outcomes and to prospectively test their validity in predicting outcomes.

Indications and management of everolimus after liver transplantation.

OBJECTIVE Our aim was to assess our experience with the use and management of everolimus after orthotopic liver transplantation (OLT). MATERIALS AND METHODS Among the 759 patients who underwent transplantation from 1988 to 2008, 25 (3.2%) received immunosuppression with everolimus. Their mean age was 55.6 years. We analyzed indications for use, time between transplantation and introduction of everolimus, as well as its efficacy, side effects, and patient survival. RESULTS The indications for everolimus treatment were: extended hepatocellular carcinoma (HCC) in the explanted liver (n = 6; 24%); HCC recurrence during follow-up (n = 4; 16%); de novo tumor (n = 6; 24%); refractory rejection (n = 3; 12%); side effects of calcineurin inhibitors (CNI; n = 3; 12%); and other causes (n = 3; 12%). Mean time between OLT and everolimus treatment was 40 +/- 33 months (range, 10 days-178 months). Mean follow-up after conversion was 10 +/- 9 months (range, 1.5-25 months). More than half of the patients resolved the event for which the drug was indicated: 75% of patients with refractory rejection; 60% of those with renal insufficiency; and 100% of those converted for neurotoxicity or hepatotoxicity. Two patients with recurrent HCC and 1 with extended HCC died at a mean time of 10.5 months. The 6 cases of de novo tumors were operated and are healthy. Side effects were dyslipidemia in 8 and infection in 2. Five patients (20%) discontinued the drug. CONCLUSIONS In the early posttransplantation period, everolimus is indicated for refractory rejection or as prophylaxis for recurrence of extended tumors. In any time but especially in the late period, everolimus is indicated for patients with serious side effects due to a CNI or to a de novo tumor.

Severe Rhabdomyolysis and Acute Renal Failure Secondary to Concomitant Use of Simvastatin With Rapamycin Plus Tacrolimus in Liver Transplant Patient

OBJECTIVE To report a severe interaction between simvastatin and rapamycin resulting in rhabdomyolysis and acute renal failure in a liver transplant patient. BACKGROUND A 56-year-old man with hepatitis C virus cirrhosis (Child B) was diagnosed with hepatocellular carcinoma and underwent liver transplantation in April 2007. He was immunosuppressed with tacrolimus (FK) and mycophenolate mofetil (MMF). Postoperative complications were arterial hypertension and renal insufficiency. In June 2007, liver dysfunction was detected and acute rejection was diagnosed by biopsy. He received three 500-mg boluses of methylprednisolone and FK levels were maintained between 10 and 12 ng/mL. Laboratory values revealed persistent rejection and MMF was stopped with initiation of rapamicin. One month later, hyperlipidemia appeared as a consequence of rapamicin therapy; simvastatin was administered. In August 2007, the patient was readmitted due to severe muscule pain and the inability to ambulate. Laboratory values were: total bilirubin 16 mg/dL, serum creatinine 4.3 mg/dL, and total creatine kinase (CK) 42,124 U/L. With the suspicion of rhabdomyolysis, leading to worsening of his basal renal insufficiency, rapamycin and tacrolimus were stopped. Hemodialysis was initiated owing to renal failure and hyperkalemia. Some hours later, the patient developed ventricular fibrillation and respiratory failure and succumbed. DISCUSSION Calcineurin inhibitors (CNI), corticosteroids, and mammalian target of rapamycin (m-TOR) inhibitors are associated with adverse dyslipidemic effects. To reduce the overall cardiovascular risk in these patients, lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have been widely used. CNI and m-TOR inhibitors, as well as most statins, are metabolized by cytochrome P450 (CYP)3A4; thus, pharmacokinetic interactions between these drugs are possible. Previous reports have indicated an increased risk of rhabdomyolysis in the presence of concomitant drugs that inhibit simvastatin metabolism. CONCLUSIONS Concomitant administration of statin therapy and drugs that inhibit cytochrome P450 (CYP)3A4 increased the risk of rhabdomyolysis in a patient suffering liver and renal dysfunction.

Our experience in liver transplantation in patients over 65 yr of age

Abstract: Objectives:  The aim of this study was to analyze short‐ and long‐term results of liver transplantation (LT) in patients over 65 yr.

Evolution of Biliary Complications After Liver Transplantation: A Single European Series

BACKGROUND The aim of this study was to analyze the evolution of biliary complications over 20 years among adult patients undergoing liver transplantation (OLT) at our institution. PATIENTS AND METHODS Between 1985 and 2007, we performed 1000 OLT in 789 adults and 211 children. To ascertain the evolution of biliary complications among adult OLT from October 1988 to September 2007, we compared the first 100 to with the last 200 adult OLT. RESULTS Duct-to-duct was the most common biliary anastomosis performed in both periods (1st; 89% and 2nd; 94%; P = NS). However, a T-tube was used more frequently in the first period (1st; 46% vs 2nd; 6.6%; P < .001). The remaining cases underwent a hepaticojejunostomy (1st; 11% vs 2nd; 7.6%). Biliary complications were more frequent in the first period (1st; 20% vs 2nd; 9%; P < .01). In the first period, the use of a T-tube caused 32% of complications, all of them being bile leaks; but there were none in the second period. Arterial thrombosis or strictures were related to biliary complications in 10% and 33.3% among the first and second periods, respectively. The severity of complications according to the Clavien classification was similar in both periods: IIIa, 15% versus 33.3%; IIIb, 55% versus 55.5%; and IV, 15% versus 11.1%, respectively (P = NS). CONCLUSION The biliary complication rate among adult patients post-OLT decreased over 20 years at our institution, probably owing to the abandonment of the routine use of a T-tube as well as to advances in immunosuppressive protocols, organ preservation, and preoperative patient management.

Liver Retransplantation in HIV‐Infected Patients: A Prospective Cohort Study

Information regarding liver retransplantation in HIV‐infected patients is scant. Data from 14 HIV‐infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV‐negative retransplanted patients. In HIV‐infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV‐positive patients was lower than in HIV‐negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV‐infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3‐year survival probability (80% and 67%, respectively), similar to that in their respective HIV‐negative counterparts (72% and 70%). In HIV‐infected and HIV‐negative patients, 3‐year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3‐year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV‐infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.

Mejoría de los resultados de la resección quirúrgica del hepatocarcinoma

Objetivo Presentar los resultados de las hepatectomias por hepatocarcinoma de una unidad especializada comparando la experiencia inicial, 1987-1993, con el segundo periodo, 1995-2000, en que se limitaron las indicaciones a los pacientes Child-Pugh A sin hipertension portal y se introdujeron mejorias tecnicas como los pinzamientos hiliares selectivos e intermitentes y una politica transfusional mas restrictiva. Pacientes Y Metodos En los ultimos 12 anos se han realizado en nuestra unidad 110 hepatectomias en 105 pacientes por hepatocarcinoma. El 80% asentaba en un higado cirrotico y la etiologia predominante fue el virus de la hepatitis C. En el segundo periodo se realizo una endoscopia digestiva alta de forma sistematica para estudiar la presencia de varices y, opcionalmente, un estudio hemodinamico para descartar una hipertension portal. Resultados En el segundo periodo se resecaron tumores mas grandes y se realizaron mas hepatectomias mayores, ya que aumentaron tambien los hepatocarcinomas en el higado no cirrotico, y ademas se transfundieron menos pacientes. La mortalidad temprana descendio del 21 al 1,8%, y la supervivencia media aumento de forma significativa de 37 a 52 meses. La supervivencia actuarial ascendio del 64 al 91% al ano y del 23 al 52% a los 5 anos, en el primer y el segundo periodos, respectivamente. La supervivencia libre de enfermedad tambien fue significativamente mejor: el 53 y el 84% al ano y el 27 y el 40% a los 5 anos en el primer y segundo periodos, respectivamente. El analisis de los resultados en los pacientes cirroticos tambien puso de manifiesto una mejoria estadisticamente significativa en la mortalidad temprana y la supervivencia. En el analisis multivariado de factores pronostico de supervivencia se evidencio que la ausencia de transfusion sanguinea, los pacientes resecados en el segundo periodo y la presencia de seudocapsula eran factores independientes de mejor supervivencia. Conclusiones Los resultados de la reseccion hepatica por hepatocarcinoma han mejorado significativamente debido a la disminucion de la mortalidad temprana gracias a una seleccion mas rigurosa de los pacientes y a las mejoras tecnicas introducidas.

Acute Antibody-Mediated Rejection as Cause of Late Liver Allograft Failure: A Case Report

BACKGROUND Despite now being an infrequent complication in liver transplantation (LT) recipients, acute liver failure is still associated with high mortality. CASE REPORT Here we report a case of acute liver failure 11 months after AB0-compatible LT in a hepatitis C-positive 50-year-old male recipient caused by late antibody-mediated rejection (AMR). De novo donor-specific antibodies appeared later in a previously negative donor-recipient crossmatch, leading to a rapid deterioration of liver function. CONCLUSIONS We highlight the importance of an accurate diagnosis and an early therapeutic intervention. The analysis of this case brings novel and generalizable insights to the differential diagnosis of acute liver failure after LT.

P0026 : The HIV infection does not have impact on survival and tumor recurrence in hepatocellular carcinoma patients treated by liver transplantation

to projected growth in prevalence based on empirical evidence of trends in risk factors such as obesity and diabetes, the primary drivers of NAFLD incidence. Results: The projected cumulative number of LTs averted for ESLD patients due to highly effective HCV treatment is estimated to be 10,490 over the period 2015–2035 (see Figure). Of this total, 7,320 livers would accrue to patients without HCV, accounting for 9% of livers used for all non-HCV liver transplants over this time period and approximately 123,700 life-years gained by non-HCV patients. Conclusions: More systematic use of highly effective treatments for HCV in the US may have substantial public health benefits for patients suffering from ESLD due to decreased liver transplantation in the HCV population. Most of these benefits accrue to patients without HCV.