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Resumen Introduccion En 2007 se consensuo un protocolo asistencial entre los tres centros de trasplante hepatico (TH) de Cataluna, que contemplaba el trasplante hepatico (TH) asociado a quimiorradioterapia neoadyuvante como tratamiento del colangiocarcinoma perihiliar (CCAp) irresecable. Objetivo Analizar la aplicabilidad del TH en los pacientes con CCAp incluidos en el protocolo y la supervivencia por intencion de tratamiento. Metodos Estudio observacional multicentrico que incluye a pacientes de edad ≤ 68 anos, diagnosticados de CCAp ≤3 cm (diametro radial), irresecable, sin afectacion ganglionar o metastasis a distancia. Los pacientes recibieron tratamiento neoadyuvante basado en radioterapia externa en una dosis total de 45 Gy, asociado con bolos de 5-fluoracilo durante los tres primeros dias de irradiacion y posteriormente capecitabina oral. Aquellos en los que no se objetivo signos de progresion se incluyeron en la lista de espera para TH. Resultados Entre 2007 y 2018, 13 pacientes fueron incluidos en dicho protocolo. Ocho de los 13 pacientes (61%) fueron trasplantados tras un tiempo en lista de espera de 122 dias (rango 5-192). La supervivencia por intencion de tratamiento a 1 y 5 anos fue del 69 y 39%. La supervivencia global post-TH a 1 y 5 anos fue del 87 y 62%, con una probabilidad de recidiva del 29% a los cinco anos post-TH. Conclusion La aplicabilidad del trasplante hepatico combinado con quimiorradioterapia neoadyuvante ha sido del 61% en nuestra serie y debe ser considerado como un tratamiento potencialmente curativo para pacientes seleccionados con CCAp irresecable y sin enfermedad metastasica.

El artículo se centra en una cuestión muy debatida como es la reacción social que se produjo en el País Vasco frente a ETA y el apoyo que la sociedad prestó a las víctimas. A este respecto se distinguen distintos períodos, desde una primera y larga etapa en la que el rechazo social a ETA fue ocasional y las víctimas no existían públicamente, a una última, ya muy reciente, en el que las cosas cambiaron y se fue manifestando la repulsa a la organización terrorista. Asimismo, el texto sirve para analizar los grupos que más firmemente se le opusieron, los mecanismos de ETA para extender el miedo y la estigmatización de una parte de la sociedad, o las políticas de algunos partidos y movimientos frente a la banda. The article focuses on the much debated question of the social reaction to ETA in the Basque Country and the support that society gave to the victims. In this respect different periods can be distinguished: from a long, first stage in which social rejection of ETA was only occasional and the victims did not exist publicly, to a final and very recent stage when things changed and expression was given to condemnation of the terrorist organization. In addition, the text serves to analyze the groups that were most firmly opposed to ETA, the latter’s mechanisms for spreading fear and stigmatizing a part of the population, and the policies of some parties and movements facing the terrorist gang.

We present a human immunodeficiency virus-infected patient with severe decompensated hepatitis C virus-related cirrhosis awaiting liver transplantation (LT) who received a 24-week course of interferon/ribavirin-free antiviral treatment with sofosbuvir and daclatasvir on a compassionate basis. Rapid viral suppression was associated with progressive improvement of his liver function tests. The patient achieved a sustained virological response and concomitant clinical improvement, which prompted removal from the LT list 12 weeks after the end of treatment.

Background Treatment with SOF/VEL for 12 weeks results in high sustained virologic response rates 12 weeks after treatment (SVR12) in genotype 1–6 HCV infected patients in clinical trials and real-world settings. The current study evaluated the safety and efficacy of SOF/VEL in adult patients with recurrent chronic genotype (GT) 1–6 HCV infection post-liver transplant. Methods This Phase 2, single-arm, open-label study evaluated 12 weeks of SOF/VEL 400/100 mg daily for 12 weeks in HCV-infected liver transplant recipients. Patients could be treatment experienced or treatment naive with no cirrhosis or compensated cirrhosis and had to be ≥3 months post-transplant with no signs of rejection at screening and history of pre-transplant chronic HCV. The primary endpoint was SVR12. Results A total of 79 patients were enrolled and treated. Of these, 81% were male, 82% were white, 9% had compensated cirrhosis, 59% were treatment-experienced, 47% had GT1, 4% GT2, 44% GT3, and 5% GT4 HCV infections. For immunosuppression, 71% of patients used tacrolimus, 24% mycophenolic acid, 14% cyclosporine, 11% azathioprine, 10% sirolimus, 6% everolimus, and 1% prednisolone. Median (range) time from liver transplantation was 7.5 (0.3–23.9) years. Rates of SVR4 for available patients are presented in the Table (IDDF2018-ABS-0109 Table 1). There was one virologic failure (relapse; GT1a, non-cirrhotic, treatment naive) and one non-virologic failure (GT1b, cirrhotic, treatment naive). All 34 GT3 HCV-infected patients including 2 with cirrhosis achieved SVR4. Complete SVR12 and viral sequencing data will be presented. There were 61 (77%) patients with adverse events (AEs). Common (>10%) AEs were headache (24%), fatigue (20%), and cough (10%). One patient discontinued SOF/VEL on Day 7 due to an AE of grade 1 hyperglycemia. No serious or severe AEs were assessed by the investigator as related to SOF/VEL, there were no episodes of liver transplant rejection, and there were no deaths. Conclusions Treatment with the single tablet regimen of SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1–4 HCV-infected liver transplant recipients with and without cirrhosis.

Aims To investigate an optimal long-term prophylactic strategy for prevention of hepatitis B virus (HBV) recurrence after liver transplantation, we conducted a randomized study of 29 transplant recipients receiving a short course of hepatitis B immune globulin (HBIg) + lamivudine (LAM), followed by randomization to long-term prophylaxis with LAM with or without HBIg. Methods The efficacy and safety, and impact on survival and HBV recurrence of these 2 prophylactic regimens were compared over a mean period of 10 years. In patients with viral recurrence, the HBV quasispecies in the surface/polymerase region were studied by ultra-deep pyrosequencing (UDPS). Results The 10-year survival rate was 76% and was not affected by the type of prophylaxis. Four patients had hepatitis B surface antigen (HBsAg) recurrence within the first 48 months after orthotopic liver transplantation (OLT). HBsAg-positive and -negative patients showed similar mean survival times, with no differences between the 2 regimens. Low HBV DNA levels were transiently detected in 32% of HBsAg-negative patients. UDPS showed major changes after OLT in the HBV quasispecies of patients with viral recurrence, which may be explained by a “bottleneck” effect of OLT together with prophylactic therapy. Conclusion Long-term survival after OLT in end-stage chronic hepatitis B patients was good with both prophylactic strategies. However, low, transient HBV DNA levels were detected even in the absence of HBsAg, showing the importance of continuing HBV prophylaxis.

The immunosuppressive management of liver transplant recipients suffering early calcineurin inhibitor-induced neurotoxicity is a challenge in daily clinical practice. We have assessed the use of everolimus as the main immunosuppressant in patients presenting severe neurotoxicity in the early post-transplantation period. From October 1988 to October 2012, 10 patients in our center received everolimus because of severe neurotoxicity in the 1st 3 months after transplantation. We analyzed several variables associated with this treatment, including patient characteristics, time from liver transplantation to conversion to everolimus, immunosuppression regimens before and after conversion, treatment efficacy, adverse events, and discontinuation after conversion. Median follow-up after conversion to everolimus was 27 months (range, 1-63 mo). Neurotoxic events were: akinetic mutism in 4 patients, repeated convulsions in 3, cerebrovascular accident in 1, Guillain-Barré syndrome in 1, and disabling tremor in 1. Treatment with calcineurin inhibitors was discontinued in all patients. Post-conversion regimens consisted of everolimus plus mycophenolate mofetil (MMF) plus steroids in 7 patients, everolimus plus MMF in 1, everolimus plus steroids in 1, and everolimus alone in 1. Liver function was maintained for ≥1 month in all patients except 1, who presented a severe rejection that was treated with steroid bolus and Neoral cyclosporine. Neurologic function was fully recovered in 8 patients. In 1 patient with akinetic mutism and another with convulsions, tacrolimus was reintroduced at 2 months and 1 month, respectively, after resolution of the neurotoxic event. Everolimus is feasible and effective as the main immunosuppressant in patients suffering severe neurotoxicity during the 1st 3 months after transplantation. It allows neurologic function to be recovered while maintaining adequate liver function.

Background Patients with hepatitis C virus (HCV) genotype 4 infection are poorly represented in clinical trials of 2nd-generation direct-acting antivirals (DAAs), and more data are needed to help guide treatment decisions. We still have even fewer data concerning liver transplant patients. Simeprevir (SIM) and sofosbuvir (SOF) combination is useful to treat this genotype. The aim of this study was to know the efficacy and safety of the combination SIM + SOF ± ribavirin (RBV) in a group of liver transplant patients with HCV genotype 4 infection in Spain in real life. Methods This was a multicenter retrospective study, including 28 HCV genotype 4 patients from 11 liver transplant centers who were treated with SIM + SOF ± RBV. We included in the analysis demographic, clinical, and virologic data and details of serious adverse events (SAEs), including mortality rate 6 months after treatment. Results All patients were male, mean age 52 ± 9.43 years, and 50% were IL28B CT and 37.5% TT; 46.42% of them were pretreated and 76.9 were null responders. Fibrosis stage 4 was found in 38.7% of patients; in 67.8% of those cases the diagnosis of fibrosis was made with the use of Fibroscan, in 21.4% by liver biopsy. The average Fibroscan was 13.86 KPa. The average Model for End-Stage Liver Disease (MELD) score of cirrhotic patients was 10.9 and the Child-Pugh score was A in 70%, B in 20%, and C in 10%. We included RBV in 75% of patients, and treatment duration was 12 weeks in all patients. The sustained virologic response at week 12 (SVR12) was 95.23%. There were no discontinuations due to SAEs, but the mortality rate at 6 months after treatment was 7.14%. All deceased patients were cirrhotic, Child C, and with an average MELD score of 20. Conclusions The combination SIM + SOF ± RBV to treat HCV genotype 4 in liver transplant patients is an option with high rates of SVR12 and very safe, similarly to genotype 1. There was no treatment-related mortality, but when it is administered in advanced stages of fibrosis it may not be enough to prevent mortality associated with cirrhotic hepatitis C recurrence after transplantation.

Presentation Poster

A major achievement for patients transplanted for hepatitis B virus (HBV) associated end-stage liver disease is the successful prevention of reinfection with high dose of hepatitis B immunoglobulin (HBIG). The introduction of lamivudine in combination with HBIG reduces recurrence rates to less than 5% at 5 years. Currently, this combination is the accepted standard regimen in most transplantation units. However, a major drawback of this therapy is that high-dose intravenous (IV) HBIG is very expensive. Several strategies have been explored to reduce such costs. These include withdrawal of HBIG at some time after transplantation while continuing lamivudine, vaccination of patients prior to cessation of HBIG and substitution of high-dose IV HBIG by low-dose intramuscular (IM) HBIG. It has been demonstrated that crucial pharmacokinetic parameters, including anti-HBs antibodies through levels at time of HBIG re-administration, do not differ significantly after IV and IM administration in stable hepatitis B surface antigen (HBsAg) negative patients with at least 12 months follow-up after orthotopic liver transplantation, confirming the cost-effectiveness of IM HBIG administration. Recent studies suggest that, compared with combination of HBIG plus lamivudine prophylaxis, the combination of adefovir plus lamivudine prophylaxis provides equivalent protection against HBV reinfection with better tolerability at a significantly lower cost. Nonetheless, HBIG continue to be the cornerstone of HBV recurrence prevention.

The prognosis after liver transplantation is related to the efficacy of prophylaxis of hepatitis B virus (HBV) graft re-infection. The risk of HBV re-infection is directly related to HBV viral load at the time of transplantation. HBV prophylaxis after transplantation with long-term administration of hepatitis B immunoglobulins (HBIG) or monoprophylaxis with lamivudine can significantly reduce the risk of HBV recurrence. Antivirals can control HBV replication in patients with decompensated HBV cirrhosis awaiting transplantation. However, there is a risk of HBV viral breakthrough during nucleo(t)side antiviral treatment. Efficacy of antivirals and the risk of viral resistance should be taken into account. The post-transplant combination of antiviral therapy and HBIG prophylaxis is very effective in reducing the rate of HBV re-infection to less than 10%, increasing the survival rate. The current 5-year survival after transplantation for HBV related liver disease is 85%. In patients without active viral replication at transplantation, the possibility of discontinuing HBIG prophylaxis over the long-term after transplantation with maintenance of antiviral treatment or HBV vaccination is under evaluation. In conclusion, the prophylaxis of HBV re-infection combining antiviral therapy prior to transplantation, and combination of HBIG and antiviral therapy post-transplantation is effective in reducing the rate of HBV re-infection.

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.

Objectives: The aim of this study was to analyze short- and long-term results of liver transplantation (LT) in patients over 65 yr. Material and methods: Between 1996 and 2004, 386 patients underwent 415 LT at our center. The main indication for LT was post-necrotic cirrhosis in 59%, followed by hepatocellular carcinoma (HCC) over cirrhosis in 33%. Half of the patients (53%) were hepatitis C virus (HCV) +. Overall, 72 patients were >65 yr of age. Actuarial survival, causes of mortality and postoperative complications were compared between groups: patients under and over 65 yr. Risk factors for poor outcome in patients over 65 yr were also analyzed. Results: The older group had more patients at Child A stage, more HCC as an indication for LT and more HCV (+) patients, p 65 yr group (p = 0.03). Main causes of mortality in patients >65 yr were recurrence of underlying disease and medical causes. In the older age group, fewer infections (p = ns) and rejections (p = 0.017) occurred in the postoperative period. Risk factor for poor outcome in the group of patients over 65 yr in multivariate analyses was pre-LT renal insufficiency (odds ratio 3.5, p = 0.002, 95% confidence interval 1.58–7.82). Conclusion: Results in patients >65 yr are comparable to those

The influence of cytomegalovirus (CMV) on recurrent hepatitis C virus (HCV) in liver grafts is controversial. Our aim was to investigate the association between CMV infection and disease and severe HCV recurrence (composite variable of presence of stage 3 to 4 fibrosis, need for retransplantation or death due to liver disease) in the first year after transplantation.An observational, prospective, multicenter study was performed. The CMV replication was monitored by determining CMV viral load weekly during hospitalization after transplantation, twice monthly in the first 3 months after discharge, and at each follow-up visit until month 12. Liver fibrosis was assessed histologically by liver biopsy or transient elastometry. Pretransplant, intraoperative, and posttransplant variables were recorded. Multiple logistic regression was performed to study the impact of CMV on severe HCV recurrence.Ninety-eight patients were included. The CMV infection was detected in 48 patients (49%) in the first year posttransplant, of which 11 patients (22.9%) had CMV disease. Twenty-three patients (23.5%) had severe HCV recurrence. Of these, 17 (73.9%) developed stage 3 to 4 fibrosis, 4 (17.4%) died, and 2 (8.7%) underwent retransplantation. Only 7 of 12 (58.3%) seronegative recipients of a seropositive donor (positive donor/negative recipient [D+/R-]) received universal prophylaxis, and 10 of 12 (83.3%) D+/R- patients developed CMV replication. In the multivariate analysis, the presence of CMV D+/R- serodiscordance (odds ratio, 6.87; 95% confidence interval, 1.89-24.99; P = 0.003), and detection of a higher peak HCV viral load (odds ratio, 3.85; 95% confidence interval, 1.49-9.94; P = 0.005) were associated with severe HCV recurrence.Our results support an association between CMV D+/R- serodiscordance and severe HCV recurrence in patients undergoing liver transplantation for HCV liver disease.

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.

Aims: To retrospectively review our liver transplant performance to identify factors that influenced early outcomes and to prospectively test their validity in predicting outcomes. Methods: Clinical records from 190 patients with liver transplants (LT; n = 200) performed between 1991 and 1997 were reviewed and the data evaluated by univariate and multivariate analyses regarding clinical outcome. The prognostic model thus obtained was prospectively evaluated in 55 patients undergoing transplant between 1999 and 2000. Results: Main indication for transplant was post-necrotic cirrhosis (61%), mostly HCV(+). The majority of patients were Child-Pugh C status (46%). Post-operative mortality at 3 months was 15.3%. Risk factors predicting death were: Child-Pugh C status (OR 1.3), pre-LT renal insufficiency (OR 5.8), malnutrition (OR 2.9) and technically complex surgery requiring cross-clamping with or without bypass (OR 4.9). None of the donor factors was significant. Prospectively applied to predict outcome in the 55 patients, the model had a sensitivity of 80% and a specificity of 88.8% with a higher-than-anticipated accuracy with a positive predictive value of 61.5% and a negative predictive value of 95.3%. Conclusions: Pre-LT renal insufficiency is the most significant risk factor for early mortality and suggests that LT should be performed before evidence of irreversible renal insufficiency becomes manifest.

To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d’Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2–129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1–112.5) months. At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p

Background Liver transplantation (LT) is the treatment of choice for chronic and acute liver failure; however, the status of long-term survivors and allograft function is not well known. Aim To evaluate the clinical outcome and allograft function of survivors 20 years post-LT, cause of death during the same period and risk factors of mortality. Methods A retrospective study was conducted from prospective, longitudinal data collected at a single center of adult LT recipients surviving 20 years. A comparative sub-analysis was made with patients who were not alive 20 years post-transplantation to identify the causes of death and risk factors of mortality. Results Between 1988 and 1994, 132 patients received 151 deceased-donors LT and 28 (21 %) survived more than 20 years. Regarding liver function in this group, medians of AST, ALT and total bilirubin at 20 years post-LT were 33 IU/L (13–135 IU/L), 27 (11–152 IU/L) and 0.6 mg/dL (0.3–1.1 mg/dL). Renal dysfunction was observed in 40 % of patients and median eGFR among 20-year survivors was 64 mL/min/1.73 m2 (6–144 mL/min/1.73 m2). Sixty-one percent of 20-year survivors had arterial hypertension, 43 % dyslipidemia, 25 % de novo tumors and 21 % diabetes mellitus. Infections were the main cause of death during the 1st year post-transplant (32 %) and between the 1st and 5th year post-transplant (25 %). After 5th year from transplant, hepatitis C recurrence (22 %) became the first cause of death. Factors having an impact on long-term patient survival were HCC indication (p = 0.049), pre-transplant renal dysfunction (p = 0.043) and long warm ischemia time (p = 0.016); furthermore, post-transplant factors were diabetes mellitus (p = 0.001) and liver dysfunction (p = 0.05) at 1 year. Conclusion Our results showed the effect of immunosuppression used during decades on long-term outcome in our LT patients in terms of morbidity (arterial hypertension, diabetes mellitus, dyslipidemia and renal dysfunction) and mortality (infections and hepatitis C recurrence).

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.

Introduction Liver transplant recipients frequently suffer gastrointestinal (GI) complications but their prevalence and their influence on quality of life remain unknown. Objective The objective of this study was to asses the prevalence, impact on quality of life, and management of GI complications in liver transplant recipients. Patients and Methods This was an epidemiologic, cross-sectional, multicenter study. Four hundred seventeen liver recipients were recruited in 14 centers. A questionnaire was filled for every patient. Results The median age of the patients was 55 years. The median time since transplantation was 4.1 ± 4 years. Whereas 19.2% presented some GI disease before transplantation, 49.4% showed this type of complication after transplantation. Diarrhea was the most prevalent GI complication, and anorexia was the GI disorder that affected patients daily activities the most frequently. GI complications were more frequent among female patients, subjects with pretransplantation hiatal hernia, and those readmitted after transplantation. Of the patients with GI complications, 70.9% received pharmacological treatment (89.7% with gastric protectors). Immunosuppressive therapy was also modified because of GI complications. Immunosuppressive drug dose was reduced in 18.1%, transiently stopped in 3.4%, and definitively stopped in 3.4% of cases. The drug most frequently changed was mycophenolate mofetil: dose reduction, 23.6%; transient withdrawal, 5.7%; and definitive withdrawal, 6.6%. Conclusions The prevalence of GI complications in the liver transplant population was approximately 50%. GI complications showed a significant impact on the quality of life of the patients. They were related to female gender, to pretransplantation GI pathology, and posttransplantation hospital admission. These complications were frequently managed with pharmacological therapy or with changes in immunosuppressive therapy.

Summary The success of current antiviral treatment for hepatitis C virus (HCV) recurrence in liver transplant (LT) recipients remains limited. We aimed at evaluating the value of IL28B genotype and early viral kinetics to predict response to standard treatment in the transplant setting. We retrospectively evaluated 104 LT recipients treated for HCV genotype 1 recurrence between 2001 and 2010. Baseline variables, including IL28B genotype, and early viral kinetics were compared among patients who did or did not achieve a sustained virological response (SVR). Logistic regression analyses of candidate variables were conducted to generate a reliable predictive model based on the minimum set of variables. Twenty-nine (28%) achieved an SVR. On multivariate analysis, the magnitude of HCV RNA decline at 4 weeks (OR: 3.74, 95% CI: 1.64–9.39; P = 0.003) and treatment compliance (OR: 35.27, 95% CI: 3.35–365.54; P = 0.003) were the only independent predictors of SVR. Favourable recipient IL28B genotype significantly correlates with virological response at week 4 (OR 3.23; 95% CI, 1.12–9.15; P = 0.03). By logistic regression analysis, a model including donor age, recipient rs12979860 genotype and viral load at 4 weeks showed the best predictive value for SVR with an area under the receiver operating curve of 0.861. Favourable recipient IL28B genotype strongly correlates with the viral response at week 4 which is the strongest predictor of response. The combination of recipient IL28B genotype and donor age with the week 4 response reliably estimates the probability of SVR early on-treatment and may facilitate therapeutic strategies incorporating new antiviral agents.

Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

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.

Survival post-liver transplantation (LT) has improved; however, patients are considered at the, risk of malignancy due to prolonged immunosuppression. The long-term outcome of patients developing de novo neoplasm (DN) at our centre was evaluated.Between October 1988 and December 2007, 800 LT were performed in 742 patients. Patients were divided into two study periods according to the time of LT; first: October 1988-December 1995; second: January 1996-December 2007.After a mean follow-up of 5 ± 4.6 years, 71 DN (9.5%) were detected in 742 patients. The cumulative risk of DN development increased with the time from LT although no differences at 3, 5, and 10 years were found when first and second periods were compared (3, 7, 16% vs. 2, 4, 11%, respectively; p = 0.4). DN incidence was higher in the first compared with the second period (10.7 vs. 7.8%; p 0.04); no significant differences were observed in mortality rate (50 vs. 27%; p = 0.052). Actuarial patient survival post-DN at 1, 3, and 5 years: 67, 48, 45% versus 82, 71, 65%, in the first versus second period, respectively, p 0.04.DN incidence has decreased in recent years; however, as survival post-LT increases, so does the incidence of DN. Surveillance programmes are necessary to diagnose DN at early stages.

The aim of this study was to ascertain the outcome of liver transplantation (LT) due to hepatocellular carcinoma (HCC) in patients who had undergone previous liver resection (LR) for HCC.A case-control study (1:2) was designed to compare patients who underwent LT due to HCC recurrence with a previous LR for HCC (study group) with those who underwent LT for primary HCC but without previous LR (control group).From January 1990 to December 2007, a total of 303 cirrhotic patients with primary HCC were evaluated for surgery. Primary LT was performed in 191 and LR in 100. When HCC recurrence was diagnosed after LR (69/100), 17 of the 69 (25%) patients underwent LT (study group). The median follow-up was 70 months (12.7-203.0 months). Disease-free survivals at 1, 3, and 5 years in the study group versus the control group were 86%, 68%, 58% vs. 97%, 93%, 89%, respectively (p0.04). The 1-, 3-, and 5-year actuarial patient survivals in the study group versus the control group were 59%, 52%, 52% vs. 85%, 76%, 65%, respectively (p = NS). Patients of the study group were divided into two groups according to the time to recurrence after LR: group 1 was1 year, and group 2 was1 year. Recurrence after LT was 75% in group 1 vs. 15.4% in group 2 (p0.03). The 1-, 3-, and 5-year actuarial patient survivals were 25%, 0%, 0% in group 1 and 69%, 69%, 69% in group 2, p0.02).Liver transplantation can be safely performed after a previous LR for HCC. Patients with recurrence during the first year after hepatectomy have a poor prognosis after LT.

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.

The aim of this study was to analyze short- and long-term results of liver transplantation (LT) in patients over 65 yr.Between 1996 and 2004, 386 patients underwent 415 LT at our center. The main indication for LT was post-necrotic cirrhosis in 59%, followed by hepatocellular carcinoma (HCC) over cirrhosis in 33%. Half of the patients (53%) were hepatitis C virus (HCV) +. Overall, 72 patients were65 yr of age. Actuarial survival, causes of mortality and postoperative complications were compared between groups: patients under and over 65 yr. Risk factors for poor outcome in patients over 65 yr were also analyzed.The older group had more patients at Child A stage, more HCC as an indication for LT and more HCV (+) patients, p0.05. No differences were observed in donor and surgery characteristics, except for lower multi-transfusion and higher incidence of grafts with steatosis in the older group (p0.05). Actuarial survival at one, three, five and 10 yr was 82%, 75%, 72%, and 70% for the65 yr group vs. 77%, 66%, 55%, and 55% for the65 yr group (p = 0.03). Main causes of mortality in patients65 yr were recurrence of underlying disease and medical causes. In the older age group, fewer infections (p = ns) and rejections (p = 0.017) occurred in the postoperative period. Risk factor for poor outcome in the group of patients over 65 yr in multivariate analyses was pre-LT renal insufficiency (odds ratio 3.5, p = 0.002, 95% confidence interval 1.58-7.82).Results in patients65 yr are comparable to those65 yr if older LT candidates are carefully selected. Overimmunosuppression should be avoided in older candidates, as its effects could worsen the pre-existing diseases common in elderly patients.

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.

Aim To analyze our results with mycophenolate mofetil (MMF) in stable liver transplantation (LT) patients presenting with adverse events (AE) related to prolonged use of calcineurin inhibitors (CNI). Methods Conversion to MMF was performed in 56 out of 323 LT patients from 91–02: 24 (43%) were converted to MMF in monotherapy and 32 (57%) to MMF + low doses of CNI. The indication for conversion was chronic renal insufficiency (CRI) in all patients. The mean time between AE and conversion was 38.7 ± 30 months ( r : 2–101 m). Post-conversion follow-up was 39 ± 20 months ( r : 3–72 m). Results The calculated creatinine clearance (Crauckoft), improved significantly in all patients. In those converted to MMF, improvement was seen during the first 18 months for urea and during the first 6 months for creatinine. In patients converted to MMF + CNI, improvement was maintained throughout the conversion period for both urea and creatinine. Eleven (19.6%) patients underwent acute rejection (2 severe episodes in the MMF group and 1 death). Hypertension was present in 31 patients but only improved in 4 (7%). Dyslipemia was found in 12 and improved in 4 (7%). DM was present in 14 and improved in 1 (2%). Conclusions Conversion to MMF in monotherapy is useful in stable LT patients with CRI due to CNI, although this result is offset by more severe rejections. Therefore, for AE secondary to CNI, we propose an early conversion to MMF + low doses of CNI as a first step. If liver function remains stable and AEs persist or progress, conversion to MMF in monotherapy is recommended, as a second step, with close monitoring of the patient.

To retrospectively review our liver transplant performance to identify factors that influenced early outcomes and to prospectively test their validity in predicting outcomes.Clinical records from 190 patients with liver transplants (LT; n = 200) performed between 1991 and 1997 were reviewed and the data evaluated by univariate and multivariate analyses regarding clinical outcome. The prognostic model thus obtained was prospectively evaluated in 55 patients undergoing transplant between 1999 and 2000.Main indication for transplant was post-necrotic cirrhosis (61%), mostly HCV(+). The majority of patients were Child-Pugh C status (46%). Post-operative mortality at 3 months was 15.3%. Risk factors predicting death were: Child-Pugh C status (OR 1.3), pre-LT renal insufficiency (OR 5.8), malnutrition (OR 2.9) and technically complex surgery requiring cross-clamping with or without bypass (OR 4.9). None of the donor factors was significant. Prospectively applied to predict outcome in the 55 patients, the model had a sensitivity of 80% and a specificity of 88.8% with a higher-than-anticipated accuracy with a positive predictive value of 61.5% and a negative predictive value of 95.3%.Pre-LT renal insufficiency is the most significant risk factor for early mortality and suggests that LT should be performed before evidence of irreversible renal insufficiency becomes manifest.