Switch to belatacept in kidney graft recipients / Cambio a belatacept en trasplante renal

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Efficacy and Safety of Therapy With Simeprevir and Sofosbuvir in Liver Transplant Recipients Infected by Hepatitis C Virus Genotype 4: Cohort Spanish Society of Liver Transplantation Cohort.

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.

Biliary complications in orthotopic liver transplantation using choledochocholedochostomy with a T-tube.

Despite significant advances in orthotopic liver transplantation (OLT), biliary tract reconstruction is still a major source of complications. Choledochocholedochostomy with a T-tube used to be the standard procedure for biliary reconstruction after OLT. However, many centers currently avoid use of the T-tube because of the high incidence of complications. Our aim was to study the biliary complications occurring at our center when end-to-end choledochocholedochostomy (EE-CC) over a T-tube was used as the standard procedure for biliary reconstruction. A retrospective review was conducted of all patients who underwent liver transplantation from February 1, 1996, to April 30, 2010. Only patients requiring any therapy to treat biliary complications were considered, whereas those with concomitant hepatic artery complications were excluded. The study cohort consisted of 743 patients who had EE-CC with a T-tube. Of these, 73 patients (9.8%) experienced any biliary complication. Anastomotic strictures occurred in 17 patients (2.3%), and non-anastomotic strictures in 2 (0.3%). Fifteen patients with anastomotic strictures were successfully treated by dilatation and stenting. Bile leakage was diagnosed in 39 patients (5.2%). Leakage occurred at the anastomosis in 15 patients (2%), and at the exit site of the T-tube in 24 patients (3.2%). Tube opening was the only treatment used in 30 patients with bile leakage (76.9%). Seven patients experienced leaks after elective T-tube removal (1%). Overall, repeat surgery to manage biliary complications was needed in 9 patients (1.2%). The mortality rate from biliary complications was 0.13%. In conclusion, EE-CC with a T-tube was followed by a low incidence of biliary complications. The complication rate after elective T-tube removal and the repeat surgery rate were extremely low. These results might challenge the current trend to avoid T-tube stenting in OLT.

Advagraf de novo in liver transplantation: a single-center experience.

UNLABELLED: Advagraf, a prolonged release formulation of tacrolimus, is administered once daily in the morning. The aim of this study was to show the results obtained in our center, analyzing the safety, efficacy, blood trough levels, and drug doses. METHODS: We analyzed 50 consecutive recipients of a first liver transplantation with 6 months follow-up. Efficacy and safety variables were collected as the incidence of acute rejection episodes, patient and graft survivals, kidney function as well as incidences of diabetes mellitus and arterial hypertension de novo. RESULTS: The incidence of biopsy proven acute rejection episodes was 10% (n = 5), none 7 of which were steroid resistant and all resolved favorably. The rate of diabetes mellitus de novo was 22% (n = 11), 7 of whom required insulin. Hypertension developed in 9 patients (18%), all of whom were treated with a single drug. The mean serum creatinine level was 1.08 ± 0.25 mg/dL, with 3 patients (6%) displaying a value ≥ 1.5 mg/dL. Patient and graft survivals were 100%. CONCLUSION: Advagraf is an effective immunosuppressant in liver transplantation with a low incidence of biopsy-confirmed acute rejection episodes. The good results for patient and graft survival with few side effects make it a useful drug for de novo liver transplantation.

Management of hepatocellular carcinoma recurrence after liver transplantation.

UNLABELLED: Management of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT) is not well established. We conducted a retrospective analysis of our results in the treatment of HCC recurrence after OLT Patients. The 23 HCC recurrences developed after 182 OLT performed for HCC within Milan criteria, had an average follow-up of 60 months. RESULTS: The median time to recurrence was 23.4 months. Surgical resection of the recurrence was possible in 11 patients, but an R-0 resection was obtained in 8 patients. Four of these 8 patients developed another recurrence, with 3 succumbing due to tumor recurrence and 1 alive at 12 months with recurrence. The other 4 patients without recurrences, include 3 who are alive at 19, 31, and 86 months and 1 who died at 32.6 months due to hepatitis C recurrence. The 3 patients with palliative resections developed recurrences. Twelve patients were rejected for surgery: 8 were treated symptomatically, 2 with systemic chemotherapy, and 2 with everolimus and sorafenib. This last treatment was also prescribed for 2 patients after R-0 surgery who are alive at 19 and 31 months and for 1 patient after R-1 surgery who is alive at 19 months. Of 15 patients who died, 13 succumbed to HCC recurrence. The average survival from transplantation was 61.7 +/- 37.5 and 48 +/- 34.3 months for patients without and with recurrence, respectively (P < .001). The survival from the recurrence was significantly higher among patients with R-0 surgery: 32.3 +/- 21.5 versus 11.9 +/- 6.9 months (P = .006). CONCLUSIONS: HCC recurrence after OLT of patients within Milan criteria was low but had a great impact on survival. Few cases are amenable to R-0 resection, but when possible it was associated with a significantly increased survival, although with an high incidence of a new recurrence. There is a rationale for the use of sorafenib and mammalian target of rapamycin based immunosuppression, which warrants randomized studies.

Prophylactic therapy with valgancyclovir in high-risk (cytomegalovirus D+/R-) liver transplant recipients: a single-center experience.

A retrospective study was performed in liver transplant patients with high risk to develop cytomegalovirus infection (CMV D+/R-) who were treated with valgancyclovir for 3 months as prophylactic therapy. The aim of this study was to determine the safety and efficacy of prophylactic therapy with valgancyclovir. Weekly CMV antigenemia was routinely assessed during the first 3 months posttransplantation, twice a month to month 6, and monthly until the end of the first year, as well as when clinically indicated. The follow-up period was 1 year. From January 2003 to February 2007, 199 liver transplantations were performed at our institution, including 23 (11%) high-risk patients for CMV infection. Median age was 47 +/- 11.6 years. Nineteen patients (70.4%) were men. Five subjects (21.7%) developed CMV infections. Three patients with positive CMV antigenemia at 3, 4, or 6 months posttransplantation were asymptomatic, while 2 (8.7%) showed gastrointestinal CMV disease at 2 months posttransplantation or CMV hepatitis at 1 month after the end of the prophylactic therapy. Treatment with intravenous gancyclovir followed by oral valgancyclovir was successful in both patients. No opportunistic infections were observed and only 1 patient developed leukopenia as an adverse event related to valgancyclovir.

Survival and hepatitis C virus recurrence after liver transplantation in HIV- and hepatitis C virus-coinfected patients: experience in a single center.

INTRODUCTION: Posttransplant hepatitis C virus (HCV) recurrence has been shown to negatively impact graft and patient survivals. It has been suggested that HCV recurrence among HIV- and HCV-coinfected transplant recipients is even more aggressive. OBJECTIVE: To compare the histological severity and survival of posttransplant HCV recurrence between HIV- and HCV-coinfected and HCV-monoinfected patients. PATIENTS AND METHODS: Among 72 adult patients who underwent primary liver transplantation at our institution for HCV-related cirrhosis between October 2001 and April 2007. We excluded one coinfected patient who died on postoperative day 5 leaving 12 HIV- and HCV-coinfected patients for comparison with 59 monoinfected patients. When listed, all coinfected patients fulfilled the criteria of the Spanish Consensus Document for transplantation in HIV patients. Immunosuppression did not differ between the two groups: all were treated with tacrolimus + steroids (slow tapering). Aggressive HCV recurrence was defined as cholestatic hepatitis and/or a fibrosis grade > or =2 during the first posttransplant year. RESULTS: Coinfected patients were younger than monoinfected patients: 45 +/- 6 years vs 55 +/- 9 years (P = .0008). There were no differences in Child score, Model for End-stage Liver Disease score, donor age, graft steatosis, ischemia time, HCV pretransplant viral load or genotype between the groups. Significant rejection episodes were also equally distributed (25% vs 14%; P = .38). Seven coinfected patients and 29 monoinfected patients developed aggressive HCV recurrences (58% vs 49%; P = .75). Median follow-up was 924 days. Global survival at 3 years was 80%. Survivals at 1, 2, and 3 years were 83%, 75%, 62% in the coinfected vs 98%, 89%, 84% in the monoinfected patients, respectively (log-rank test = 0.09). CONCLUSIONS: The severity of histological recurrence was similar among HIV- and HCV-coinfected and monoinfected HCV liver recipients in the first posttransplant year. Mortality attributed to recurrent HCV was similar in the groups. There were no short-term (3-year) differences in survival between the two groups of patients.

Trasplante en el hepatocarcinoma: indicaciones y tratamiento previo / No disponible

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[The nutritional status of patients with colorectal cancer undergoing chemotherapy]. / Estado nutricional de pacientes con cáncer colorrectal en tratamiento con quimioterapia.

OBJECTIVE: Determine the nutritional status of patients with colorectal cancer undergoing chemotherapy and assess how many patients could benefit from nutrition facts. METHOD: Patients of both sexes aged over the age of 18 with colorectal cancer who were receiving chemotherapy between March and April 2005 were included. The nutritional status of these patients was evaluated using the method "Patient-Generated Subjective Global Assessment" (PG-SGA). According to this questionnaire, the patients were classified in one of four levels of intervention (a) no intervention required; b) nutrition education; c) nutritional intervention; d) critical intervention) and into one of three nutritional status (well-nourished, moderately malnourished or severely malnourished). RESULTS: All the patients with colorectal cancer receiving chemotherapy during the two months indicated (33 patients): 9.1% were in stage II of the disease, 21.2% in stage III and 69.7% in stage IV. The 69.7% was receiving cytostatics associated with moderate risk of malnutrition while 30.3% received low-risk chemotherapy. 57.6% of the patients were well-nourished. However, the intervention was critical in 42.4% of the patients. CONCLUSIONS: The majority of the patients studied require some type of nutritional act, although not all of them suffer from malnutrition.

Estado nutricional de pacientes con cáncer colorrectal en tratamiento con quimioterapia / The nutritional status of patients with colorectal cancer undergoing chemotherapy

Objetivo: Determinar el estado nutricional de los pacientes concáncer colorrectal en tratamiento con quimioterapia y valorar cuántospacientes podrían beneficiarse de recomendaciones nutricionales.Método: Se incluyeron pacientes de ambos sexos, mayores de18 años, con cáncer colorrectal que estaban recibiendo quimioterapiaentre marzo y abril de 2005. Se valoró su estado nutricionalmediante el método “Valoración Global Subjetiva Generada por elPaciente (PG-SGA). Según este cuestionario, los pacientes fueronclasificados en uno de los cuatro niveles de intervención: a) no requiereintervención; b) educación nutricional; c) intervención nutricional,y d) intervención crítica y en uno de los tres estados de nutrición(bien nutrido, moderadamente malnutrido o severamentemalnutrido).Resultados: Se valoraron todos los pacientes con cáncer colorrectalque recibieron quimioterapia en los dos meses señalados (33 pacientes):el 9,1% presentaba estadio II de la enfermedad; el 21,2%,estadio III, y el 69,7%, estadio IV; el 69,7% estaba recibiendo citostáticosasociados con riesgo moderado de desnutrición mientras queel 30,3% recibía quimioterapia de bajo riesgo. El 57,6% de los pacientesse encontraba bien nutrido. No obstante, la intervención fuecrítica en el 42,4% de los pacientes.Conclusiones: La mayoría de los pacientes estudiados requieren algúntipo de actuación nutricional, aunque no todos presentan malnutrición

Objective: Determine the nutritional status of patients with colorectalcancer undergoing chemotherapy and assess how many patientscould benefit from nutrition facts.Method: Patients of both sexes aged over the age of 18 with colorectalcancer who were receiving chemotherapy between Marchand April 2005 were included. The nutritional status of these patientswas evaluated using the method “Patient-Generated SubjectiveGlobal Assessment” (PG-SGA). According to this questionnaire,the patients were classified in one of four levels of intervention (a)no intervention required; b) nutrition education; c) nutritional intervention;d) critical intervention) and into one of three nutritional status(well-nourished, moderately malnourished or severely malnourished).Results: All the patients with colorectal cancer receiving chemotherapyduring the two months indicated (33 patients): 9.1% were instage II of the disease, 21.2% in stage III and 69.7% in stage IV. The69.7% was receiving cytostatics associated with moderate risk ofmalnutrition while 30.3% received low-risk chemotherapy. 57.6% ofthe patients were well-nourished. However, the intervention was criticalin 42.4% of the patients.Conclusions: The majority of the patients studied require some typeof nutritional act, although not all of them suffer from malnutrition

Liver transplantation for hepatocellular carcinoma in cirrhotic patients.

A consecutive series of 88 patients underwent transplantation for hepatocellular carcinoma with cirrhosis over a 7-year period. Liver transplantation was indicated because of the tumor in 75 cases (85.2%); tumor was an incidental finding in 13 cases (14.8%). One patient was retransplanted due to primary nonfunction. The perioperative mortality was 4.5%. Tumor recurrence was observed in seven patients (7.95%) with incidental tumor recurrence in one case. As in patients with known primary liver tumors pretransplant, a thorough follow-up is advisable to establish an early diagnosis of recurrence. The actuarial survival for nonincidental hepatocellular carcinoma at 1, 3, and 5 year was 92%, 77%, and 75%, respectively. The differences in actuarial survival between hepatitis C negative and positive hepatocellular carcinoma were not significant (log-rank test P=.27), though there was a clear improvement in results (94%, 85%, and 78% vs 90%, 71%, and 71%), at 1, 3, and 5 years meaning that HCV infection is an important prognostic factor. Although transplantation for HCC has the advantages of removing the tumor and the cirrhotic liver, it remains a controversial topic. In our experience patients showing lesions less than 5 cm or three or fewer lesions experience an equivalent survival to transplanted patients who do not have cancer.

"Pseudoseptic" pseudogout associated with hypomagnesemia in liver transplant patients.

Hypomagnesemia has been associated with deposition of calcium pyrophosphate dihydrate crystals in articular structures, causing pseudogout, also known as calcic gout. Occasionally, pseudogout may mimic septic arthritis; this "pseudoseptic" attack may be of especial concern in the immunocompromised host, such as transplant recipient patients, who may be indeed at risk of developing septic arthritis. We report the cases of two patients in whom pseudogout developed after liver transplantation. Synovial fluid appearance and leukocyte counting in synovial fluid mimicked septic arthritis, but calcium pyrophosphate dihydrate crystals were observed. Magnesium depletion before transplantation and further tacrolimus-induced renal magnesium leakage were probably working in these patients.

[Infection after orthotopic liver transplantation: analysis of the first 120 consecutive cases]. / Infección después del trasplante hepático ortotópico: análisis de los 120 primeros casos consecutivos.

OBJECTIVE: To report the infectious complications and presentation time of the first 120 consecutive liver transplants performed at our institution. METHODS: Prospective study of infectious complications among 120 consecutive adult patients who received orthotopic liver transplantation at Hospital de Cruces, from February 1996 to November 1998. Two patients received a renal transplant concomitantly. The same surveillance protocols were used for all patients and the criteria used to define infections were those reported by other authors. RESULTS: The group consisted of 120 patients, 95 males and 25 females. The age ranged from 20 and 66 years (mean: 54 +/- 9 years). The indications for transplantation included alcoholic cirrhosis (47%), HCV cirrhosis (20%), hepatocellular carcinoma (17.5%), fulminant hepatitis (6%), primary biliary cirrhosis (2.5%) and miscellaneous conditions (7%). Three patients required retransplantation. Acute rejection was histologically diagnosed in 38 patients (31%). None of the patients had corticosteroid-resistant rejection. Fifty-one patients (42.5%) developed 76 episodes of severe infection, which included: 48 episodes of bacterial infection among 33 patients (27.5%), tuberculosis in 7 patients (6%), 9 episodes of fungal infection among 8 patients (7%) and cytomegalovirus (CMV) infection among 8.5% of patients. No patient developed Pneumocystis carinii pneumonia. Fifteen (12.5%) patients died: six (12.5%) with active infection, and in four of them the infection was considered the cause of death. CONCLUSIONS: Infection rates due to bacteria and fungi were similar to those reported in the literature. A high rate of tuberculosis was found, which possible correlated with the high incidence of this disease in the general population. The low incidence of CMV infection was probably due to the preemptive therapy with gancyclovir. Trimethoprim-sulfamethoxazol prophylaxis against Pneumocystis carinii was highly effective.

Infección después del trasplante hepático ortotópico: análisis de los 120 primeros casos consecutivos / Infection after orthotopic liver transplantation: analysis of the first 120 consecutive cases

Objetivo. Describir las complicaciones infecciosas y tiempo de presentación en los 120 primeros trasplantes hepáticos consecutivos realizados en nuestro centro. Métodos. Estudio prospectivo de las complicaciones infecciosas que presentaron 120 pacientes adultos consecutivos que recibieron trasplante hepático ortotópico en el Hospital de Cruces entre febrero de 1996 y noviembre de 1998. Dos pacientes recibieron simultáneamente trasplante renal. En todos los pacientes se realizaron los mismos controles de vigilancia y los criterios para definir las infecciones fueron los descritos por otros autores. Resultados. Del grupo total, 95 eran varones y 25 mujeres. La edad osciló entre 20 y 66 años (media: 54 ñ 9 años). Las indicaciones de trasplante fueron: cirrosis alcohólica (47 por ciento), cirrosis por virus de la hepatitis C (VHC) (20 por ciento), carcinoma hepatocelular (17,5 por ciento), hepatitis fulminante (6 por ciento), cirrosis biliar primaria (2,5 por ciento) y otras indicaciones (7 por ciento).Tres pacientes precisaron retrasplante. Se diagnosticó histológicamente rechazo agudo en 38 pacientes (31 por ciento). Ninguno presentó rechazo corticorresistente. Cincuenta y un pacientes (42,5 por ciento) desarrollaron 76 episodios de infección grave, que correspondían: infección bacteriana, 48 episodios en 33 pacientes (27,5 por ciento); tuberculosis, 7 pacientes (6 por ciento); infección fúngica, 9 episodios en 8 pacientes (7 por ciento), y enfermedad por citomegalovirus (CMV) el 8,5 por ciento de los pacientes. Ningún paciente desarrolló infección por Pneumocystis carinii. Fallecieron 15 (12,5 por ciento): seis (40 por ciento) con infección activa y en cuatro de ellos la infección se consideró causa mayor de la muerte. Conclusiones. La tasa de infecciones por bacterias y hongos es similar a la recogida en la literatura. Encontramos una tasa alta de tuberculosis, que se corresponde posiblemente con la alta incidencia de esta enfermedad en la población general. La baja incidencia de enfermedad por CMV la asociamos con el tratamiento anticipado con ganciclovir. La profilaxis con trimetropin-sulfametoxazol es altamente eficaz frente a Pneumocystis carinii (AU)

Diagnostic yield and endoscopic patterns of laparoscopy in the diagnosis of granulomatous hepatitis.

In reviewing 54 cases of granulomatous hepatitis (GH) diagnosed among 2,620 laparoscopies, we have been able to classify the capsular GH changes into five patterns: Macular, exudative, pinpoint, granular and cord-like. The exudative pattern was the most frequent one, and predominated in brucellosis. The granular pattern was most common in tuberculosis. Furthermore, 35 additional cases, in whom a laparoscopic diagnosis of GH was not confirmed by liver biopsy, showed a trend to a final diagnosis consistent with multifocal diseases, whenever laparoscopic pictures were similar to the patterns described herein. We speculate with the limits associated with the use of only a single biopsy sample. We conclude that laparoscopy permits the establishment of a tentative diagnosis of GH, which could provide us with valuable information about the usefulness of obtaining multiple hepatic biopsies.