R. Bárcena

Aspergillus antigenemia sandwich-enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients.

BACKGROUNDnInvasive aspergillosis (IA) is an important cause of mortality in liver transplant patients. Clinical and microbiological diagnosis is difficult, and it is frequently achieved only after autopsy. Early diagnosis and antifungal therapy could improve the survival of these patients.nnnMETHODSnA retrospective case-control study of IA in liver transplant recipients (OLT) was performed to determine the value of the detection of galactomannan Aspergillus antigen in serum using a sandwich-ELISA test (Platelia, Sanofi Diagnostic Pasteur). Stored frozen serum specimens obtained during the posttransplantation period were used.nnnRESULTSnFourteen cases of IA were diagnosed in 240 OLT recipients (IA incidence: 5.8%) during 5 years with 13 deaths (mortality: 93%). Nine case patients and 33 control patients met the criteria required for being considered valid for antigenemia analysis. In five of the nine case patients, a serum sample was positive for Aspergillus antigenemia detection. The median value was 5.7 ng/ml (range: 1.6-6.6). Sensitivity of the test was 55.6%, specificity was 93.9%, the positive predictive value was 71.4%, and the negative predictive value was 88.6%. The likelihood ratio of a positive test was 9.2.nnnCONCLUSIONSnGalactomannan detection in serum could be useful for an early diagnosis of IA in OLT recipients.

Selection ofCandida glabrata strains with reduced susceptibility to azoles in four liver transplant patients with invasive candidiasis

The cases of four liver transplant recipients who developed invasive candidiasis (2 cholangitis, 1 perihepatic abscess, 1 candidemia) due to azole-resistantCandida glabrata are reported. Three patients were receiving azolic compounds (2 itraconazole, 1 fluconazole) when the infection was diagnosed. All four patients received fluconazole as intestinal decontamination during the first three weeks post transplantation. The infections occurred two months after transplantation in all patients, and in one patientCandida infection was the direct cause of death. Infection of the biliary tree was the origin of candidiasis in three patients; the fourth patient developed neutropenic-related candidemia. Fluconazole MICs exceeded 16 μg/ml in all cases; itraconazole MICs were 16, 2, 1, and 2 μg/ml, respectively. The potential role ofCandida species other thanalbicans in these patients after administration of azole agents is discussed.

False-positive results of Aspergillus galactomannan antigenemia in liver transplant recipients.

Background. Aspergillus galactomannan (GM) antigenemia is an early marker of invasive aspergillosis (IA), but may yield false-positive results. A prospective study, testing GM periodically in serum samples of liver transplant recipients, was performed. Methods. An index more than or equal to 0.5 were considered positive. Positive GM in samples from patients without any other criteria of proven or probable IA was considered as false-positive. The test was performed weekly during the first month after transplantation. Results. Three patients developed IA. In total, 414 serum samples from 85 liver transplant recipients were analyzed. Mean number of samples per patient (out of those who could be assessed) was 4.8. The number of false-positive GM samples was 40 (9.6%), corresponding to 28 patients. The frequency of false-positive results in samples obtained during the first week posttransplantation was 36% (27 of 75), significantly higher than the number of false-positive samples obtained after the first week (3.8%; 13 of 339; P<0.001). Multivariate analysis showed that antibacterial prophylaxis with ampicillin was the only independent factor associated with a false-positive result. Different vials of &bgr;-lactam antibiotics were tested for GM. We obtained a positive GM value (>0.5) in four of the six vials of ampicillin, in three of the six vials of piperacillin-tazobactam, in none of the six vials of cefotaxime, and in none of the six controls. Conclusions. The present study suggests that the administration of ampicillin as antibacterial prophylaxis during the first days after transplantation could be a possible cause of false-positive GM results.

The effect of liver transplantation on circulating levels of estradiol and progesterone in male patients: Parallelism with hepatopulmonary syndrome and systemic hyperdynamic circulation improvement

The correction of hepatopulmonary syndrome (HPS) after liver transplantation (LT) remains controversial. The aims of our study were to: 1) analyze whether LT reverses HPS; 2) note any relationship between HPS and the systemic hemodynamic disturbance; and 3) note changes in circulating sex hormones and the possible association with pulmonary and systemic hemodynamic changes. Systemic hemodynamic parameters, cardiac output and systemic vascular resistance (SVR), sex hormones, and intrapulmonary vasodilatation assessed by contrast transesophageal echocardiography, and gas exchange abnormalities were investigated in 19 patients with advanced cirrhosis prior to and 6 months (176.8±30 days) after LT. LT was followed by a marked reduction in cardiac output (6.6±1.7 vs 3.5±0.5 l/min; plt0.001) and SVR (1039±460 vs 1978±294 dyn⊙sec⊙cm−5; plt0.005). Before LT, circulating estradiol and progesterone levels were invariably elevated (66±22 pg/ml and 1.8±1.1 ng/ml, respectively, normal values lt31 pg/ml and 0.35 ng/ml, respectively), and dropped after LT (28±12 pg/ml plt0.001 and 0.38±0.2 ng/ml; plt0.001, respectively). Seventeen of 19 patients had intrapulmonary vasodilatation and increased alveolar-arterial oxygen difference, thereby fulfilling diagnostic criteria for HPS. Patients with HPS presented higher cardiac output (plt0.05), lower SVR (plt0.01), and higher progesterone and estradiol levels than patients without HPS (plt0.05). LT produced normalization of intrapulmonary vasodilatation in all patients. LT normalized hyperdynamic circulation and is a useful therapeutic option in patients with HPS. Normalization of sex hormone levels after LT suggests that they could play a pathogenic role in the development of HPS.

Severe Sirolimus-Related Inflammatory State Anemia in an HIV+ Liver Transplant Patient With Calcineurin Inhibitor Renal Insufficiency: A Case Report

Although multifactorial anemia is common following orthotopic liver transplantation (OLT), the late introduction of sirolimus (SRL) has been associated with high rates of anemia, whose pathogenic mechanisms have not been fully studied. Herein we have described a case of severe anemia in an HIV+ OLT patient who was switched from calcineurin inhibitors (CNI) to SRL due to severe nephrotoxicity. After 22 weeks of SRL, hemoglobin levels dropped 4 g/dL to a nadir of 6.5 g/dL. After discarding other causes for anemia, we concluded that it displayed the features of anemia of a chronic inflammatory state (ACIS): decreased mean corpuscular volume (MCV), low serum iron despite high ferritinemia, and elevated fibrinogen and C-reactive protein (CRP) levels. SRL trough levels were never above the therapeutic range. After blood transfusions and erythropoietin (EPO) use, SRL was maintained within the lower range of therapeutic levels, with significant improvement in renal function. As described among kidney transplant recipients, SRL-related anemia in this HIV+ patient with CNI nephrotoxicity after OLT showed features of ACIS. Blood transfusions and EPO use allowed SRL maintenance.

24 HIGHER SUSTAINED VIROLOGIC RESPONSE AND HISTOLOGIC IMPROVEMENT IN RECURRENT HEPATITIS C AFTER PEGYLATED INTERFERON PLUS RIBAVIRIN THERAPY UNDER CYCLOSPORINE-BASED VERSUS TACROLIMUS-BASED IMMUNOSUPPRESSIVE THERAPY

24 HIGHER SUSTAINED VIROLOGIC RESPONSE AND HISTOLOGIC IMPROVEMENT IN RECURRENT HEPATITIS C AFTER PEGYLATED INTERFERON PLUS RIBAVIRIN THERAPY UNDER CYCLOSPORINE-BASED VERSUS TACROLIMUS-BASED IMMUNOSUPPRESSIVE THERAPY M. Navasa, T. Casanovas, M. Berenguer, I. Fernandez, M. Salcedo, L. Castells, J. Pascasio, J. Fernandez, I. Herrero, A. Otero, S. Tome, M. de la Mata, R. Barcena, I. Banos, M. Guilera, on behalf of ReViS-TC Study Group. Hospital Clinic i Provincial, Barcelona, Hospital de Bellvitge, L’Hospitalet de Llobregat, Hospital La Fe, Valencia, Hospital 12 de Octubre, Hospital Gregorio Maranon, Madrid, Hospital Vall d’Hebron, Barcelona, Hospital Virgen del Rocio, Sevilla, Hospital de Cruces, Bilbao, Cĺinica Universitaria Navarra, Pamplona, Hospital Juan Canalejo, A Coruna, Hospital Santiago, Santiago de Compostela, Hospital Reina Sofia, Cordoba, Hospital Ramon y Cajal, Hospital Puerta Hierro, Madrid, Novartis Farmaceutica, S.A., Barcelona, Spain E-mail: teresacasanovas@bellvitgehospital.cat

Hepatitis C Virus Sensitivity to Combined Antiviral Therapy in Liver Transplant Versus Immunocompetent Patients

Recurrent hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) frequently causes allograft failure, because viral aggressiveness has been shown to be increased among immunosuppressed patients. Several studies have reported lower efficacy of antiviral therapy after OLT associated with worse tolerability. The aim of this study was to compare the logarithmic falls in viral loads at 4 and 12 weeks of treatment with pegylated interferon alpha and ribavirin among OLT versus immunocompetent patients. OLT patients (group 1) were recruited from 3 Spanish centers. Two age- and sex-matched controls (group 2) were randomly assigned to each case. We excluded coinfection with human immunodeficiency virus or hepatitis B or cholestatic hepatitis. Among group 1 (n = 66) were 72.7% men with an overall mean age of 52.7 +/- 10.1 years; 90.9% were genotype 1. The mean baseline viral load was 6.0 +/- 0.6 log10 IU/mL, and 19% of patients had cirrhosis. Among group 2 (n = 132) were 72.7% men with an overall mean age of 50.1 +/- 10.1 years; 92.4% were genotype 1. The mean baseline viral load was 5.9 +/- 0.5 log10 IU/mL, and 17% of patients had cirrhosis. There were no significant differences in patient characteristics between the 2 groups. The logarithmic falls in viral loads at 4 weeks of treatment were similar in groups 1 and 2: 2.3 +/- 2.1 vs 2.4 +/- 1.9 log10 IU/mL (P = .49); they were also similar at 12 weeks of treatment: 3.9 +/- 1.9 vs 3.7 +/- 2.4 log10 IU/mL (P = .66). In conclusion, in our study HCV sensitivity to combined antiviral therapy was the same among transplant versus immunocompetent patients.

TT Virus (TTV) prevalence in liver transplantation recipients

TT VIRUS (TrV) PREVALENCE IN LIVER TRANSPLANTATION RECIPIENTS S. del Campo l, N. Moreno ~, J. Moreno l, M. Lumbreras 2, M. Gomez 2, R. Uarcena ~ ~S. de Gastroenterologia, H. U. de Getafe, Getafe, Madrid, Spain. 2S. de Digestivo, H. U. de Getafe, Getafe, Madrid, Spain. O b k t t ~ Tosmdy~ TIV ~ i n l i t = ~ ~ Palim~ m d ~ We have studied 34 ~ ~ ~ ~ . ~ -~; . •, (OLT), 28 mai~,i-cm abe 513-~.73era, ~ a~ase 6:k7,s4~ohad X leest 1 ~ e ~ ~ . Tae e~_ t R ~ l i ~ r ~ pmOLT ~em akxtt01ic ~hmis in 1 9 ~ p m ~ y h l i y ~ ( l ~ i ~ 4 , h ~ c ~ i . . , u in 1, ~ I-~/+in 8 md cintx~ I-~Ar+ in 2 Weha~e e,~l e .=10) or ~ £ .m~ (Va; n=24) ~ vkal i~ec~n by I-LW or I-~Ar p~OLT. We ha~ aim malymt and h , . ~ l ~ m m , the .,.,...~...;,9~i~ ;.-.~,,~t and