Single-Nucleotide Polymorphism of CYP3A5 Impacts the Exposure to Tacrolimus in Pediatric Renal Transplant Recipients: A Pharmacogenetic Substudy of the TWIST Trial.

BACKGROUND: The pharmacokinetics of tacrolimus (TAC) and mycophenolic acid (MPA) are highly variable. An impact of single-nucleotide polymorphisms (SNPs) of the genes coding for enzymes and transporters involved in the pharmacokinetics of TAC and/or MPA is intuitively conceivable. Accordingly, we sought to analyze the influence of different SNPs on TAC and MPA exposure in pediatric renal transplant recipients. METHODS: A subpopulation of 37 patients (median age: 12.8 years, range 2.2-18.3 years) participating in the TWIST study was included in the analysis of SNPs of CYP3A5, ABCB1 (MDR1), ABCG2, SLCO1B3 (coding for OATP2), ABCC2 (coding for cMOAT), and UGT1/2. TAC trough concentrations and abbreviated area under the concentration-time curves (AUC) of MPA were measured on days 7, 28, 91, and 183 after transplant. Both of these were adjusted to the respective dose the patient received. RESULTS: The allele frequencies of analyzed SNP's were comparable to those reported previously for white populations. Dose-adjusted trough concentrations of TAC were approximately 60% lower in patients with the CYP3A5*1/*3 allele as compared with the CYP3A5*3/*3 allele (P = 0.004). Steroid-free patients in CYP3A5*3/*3 and CYP3A5*1/*3 carrier subgroups had comparable dose-adjusted TAC concentrations to the subgroup on steroids (P = 0.13). Patients younger than 10 years had a significantly lower median dose-adjusted TAC C0 concentration than patients older than 10 years; this age effect was comparable in heterozygous and homozygous CYP3A5 carriers as well as in patients on and off steroid medication. As for MPA, the genetic variability of transporters or enzymes had no impact on dose-adjusted MPA-AUC due to the low allele frequencies. Patients off steroids had a higher dose-adjusted MPA-AUC (0.18 mg·h/L per mg/m, 0.012-0.27) compared with patients on steroids (0.12 mg·h·L·mg, 0.09-0.19; P = 0.04). CONCLUSIONS: Genetic variability of CYP3A5 has an impact on TAC metabolism in pediatric renal transplant recipients, contributing partly to the variability of TAC exposure. Therefore, adjusting initial TAC dosing to the genotype of CYP3A5 might be of clinical benefit.

Conversion to tacrolimus once-daily from ciclosporin in stable kidney transplant recipients: a multicenter study.

This 24-week, open, single-arm, prospective, multicenter study evaluated the effects of conversion from ciclosporin to Tacrolimus QD in adult kidney transplant patients. Stable patients receiving ciclosporin were converted to Tacrolimus QD at 0.1mg/kg/day. Relative change in renal function (primary endpoint) was assessed using estimated creatinine clearance (eCrCl) with a noninferiority margin set at -10%. A total of 346 patients were enrolled; and 301 patients were treated per protocol (PPS) in the hyperlipidemia (n=42), hypertrichosis (n=106), hypertension (n=77) and gingival hyperplasia (n=76) groups. Relative change in eCrCl was -0.6% in all PPS patients (95% CI, -2.2; 0.9) and -5.3% in the hyperlipidemia (CI, -9.59; -0.97), 0.9% in the hypertrichosis (CI, -2.59; 4.45), -0.1% in the hypertension (CI, -3.8; 3.68), and -1% in the gingival hyperplasia groups (CI, -4.63; 2.65) (PPS), meeting noninferiority criteria. There was no acute rejection. Decreases in serum lipids and blood pressure were moderate but without meaningful change in the number of treatment medications. Substantial decreases in severity of ciclosporin-related cosmetic side effects were evident from investigator and patient self-report of symptoms. Renal function remained stable after conversion to Tacrolimus QD. The effect of conversion on cardiovascular parameters was not clinically meaningful, however, marked improvement in ciclosporin-related cosmetic side effects was observed. (ClinicalTrials.gov number: NCT00481481).

[The first successful adult right-lobe living donor liver transplantation in Hungary]. / Az elsô sikeres élô donoros felnôttkori jobb lebenyes májtranszplantáció Magyarországon.

The authors report on their experiences related to the first adult live donor liver transplantation performed in Hungary. The transplantation was done between brother and sister on 19th of November, 2007. The right lobe of the 33-year-old healthy male's donor liver (segments 5-8) was removed and implanted into the 23-year-old female suffering from cirrhosis on the ground of autoimmune hepatitis. The implantation of the right liver lobe was done after own hepatectomy in orthotopic position. Liver function has improved rapidly following the transplantation. The donor was discharged on the 10th post-operative day with stable liver function. He had full rehabilitation, got back to work, and control check-ups showed a significant liver regeneration. Two years after transplantation, the recipient also lives an active life with compensated liver function and she is under regular medical check-up. With the case report, authors overview the indications and techniques of living donor right-lobe liver transplantation.

HLA-DQ3 is a probable risk factor for CMV infection in high-risk kidney transplant patients.

BACKGROUND: Cytomegalovirus (CMV) infection in transplant patients with special risk factors remains a major hazard. CMV-seronegative recipients with seropositive donors have the highest risk of developing acute CMV disease. We suggest that the HLA-type may influence the occurrence and the severity of primary CMV infection of these recipients and the measurement of the special HLA-types may be useful in the prediction of acute infection. METHODS: Since 1999 1213 cadaver kidney transplantations have been performed in our clinic. 163 of 1213 recipients were CMV-seronegative (13%) and 129 of them received the kidney from seropositive donors. All 129 patients received CMV infection prophylaxis. Of 129 CMV-seronegative patients 49 developed acute CMV infection (38%) during the first posttransplant year. CMV infection was diagnosed by CMV antigenemia test and serologic measurements (ELISA). The particular HLA-genotypes of the recipients were studied before the transplantation. The occurrence and the severity of CMV infection was investigated in association with HLA-types. RESULTS: We found different acute CMV infection distribution in the careers and non-careers of investigated HLA-types: HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6 and HLA-DR11, but the differences were not significant in these HLA-types (P = 0.26, P = 0.37, P = 0.83, P = 0.07 and P = 0.37). While investigating HLA-DQ3, we found that of 68 DQ3-positive patients 32 (47%), of 61 DQ3-negative patients 17 (28%) had acute CMV infection and this difference was found to be significant. This result was confirmed by univariate and multivariate Cox Regression (P = 0.001) and the appropriate significance level was considered by Bonferroni correction. CONCLUSIONS: HLA-DQ3 was found to be an independent predictor of CMV infection. Our data suggest that patients positive for HLA-DQ3 are more susceptible to CMV infection than a comparable group of patients negative for HLA-DQ3. This result was not due to rejection and/or treatment for rejection and was not influenced by induction therapy. Although we found more symptomatic infections among DQ3+ patients the difference was not significant (P = 0.19). Comparing the gender proportion among all 1213 kidney recipients and among CMV-seronegative recipients we found that the proportion of males is significantly higher among CMV-seronegative recipients (P < 0.001).

Drug-induced liver graft toxicity caused by cytochrome P450 poor metabolism.

UNLABELLED: What is already known about this subject. The activity of drug-metabolizing enzymes, primarily cytochrome P450 enzymes, can determine a patient's response to a drug. Therapeutic failure or drug toxicity in the postoperative period after liver transplantation is influenced by the drug metabolizing capacity of the graft. Dose adjustment or selection of an alternative drug, which is not a substrate for the polymorphic enzyme may prevent the development of side-effects in recipients of poor metabolizer liver grafts. What this study adds. A validated analytical system with metabolomic tools has been developed to estimate the drug-metabolizing capacity of transplanted liver, which allows the prediction of potential poor metabolizer phenotypes of donors and facilitates the improvement of individual recipient therapy. In the test of drug-metabolizing status, one of the liver grafts was found to be a CYP2C9 poor metabolizer, while the other was a CYP2C19 poor metabolizer. Rationalization of the medication resulted in the recovery of both the grafts and the recipients within 1 week. AIMS: The drug-metabolizing capacity of transplanted liver highly influences drug efficacy or toxicity, particularly in the early postoperative period. The aim of our study was to predict therapeutic failures or severe adverse drug reactions by phenotyping for cytochrome P450 (P450) polymorphism resulting in reduced or no activity of the key drug-metabolizing enzymes. METHODS: A validated analytical system with metabolomic tools has been developed for estimation of the drug-metabolizing capacity of transplanted liver, which allows the prediction of potential poor metabolizer phenotypes of donors and facilitates improvement of the individual recipient therapy. RESULTS: Of the 109 liver donors in Hungary, the frequency of poor metabolizers was found to be 0.92%, 5.5% and 8.3% for CYP2C9, CYP2C19 and CYP2D6, respectively. In the present study, two liver grafts transplanted in paediatric recipients were reported to be poor metabolizer phenotypes. The liver grafts presented normal function in the early postoperative days; 2 weeks after transplantation, however, increasing liver enzymes were detected. Histological investigation of a liver biopsy suggested drug toxicity. The test of drug metabolizing status showed one of the liver grafts to be a CYP2C9 poor metabolizer, and the other was found to be a CYP2C19 poor metabolizer. Rationalization of the medication resulted in the recovery of both the grafts and the recipients within 1 week. CONCLUSIONS: Prospective investigation of the P450 status may lead to the optimization of drug choice and/or dose for a more effective therapy, avoid serious adverse effects, and decrease medical costs. Phenotyping donor livers and tailored medication can contribute to the improvement of graft and recipient survival.

Experimental results and clinical impact of using autologous rectus fascia sheath for vascular replacement.

Vascular complications are major causes of graft failure in liver transplantation. The use of different vascular grafts is common but the results are controversial. The aim of this study was to create an 'ideal' arterial interponate for vascular replacements in the clinical field. An autologous, tubular graft prepared from the posterior rectus fascia sheath was used for iliac artery replacement in dogs for 1, 3, 6 and 12 months. Forty-one grafts were implanted and immunosuppression was used in separate groups. The patency rate was followed by Doppler ultrasound. Thirty-seven grafts remained patent, 2 cases with thrombosis and 2 cases with stenosis occurred. There was no evidence of necrosis or aneurysmatic formation. The histological analysis included conventional light microscopic and immunohistochemical examinations for CD34 and factor VIII. The explanted grafts showed signs of arterialisation, appearance of elastin fibres, and smooth muscle cells after 6 months. Electron microscopy showed intact mitochondrial structures without signs of hypoxia. In conclusion, the autologous graft presents acceptable long-term patency rate. It is easy to handle and the concept of beneficial presence of the anti-clot mesothelium until endothelialisation seems to work. The first clinical use was already reported by our group with more than 2 years survival.

[Imaging techniques for the pre- and postoperative evaluation of recipients with living-donor liver transplantation]. / Elo donoros májátültetés recipienseinek pre- és posztoperatív képalkotó vizsgálatai.

Whole-liver transplantation is a worldwide-accepted method for treatment of end-stage liver disease. As a result of the shortage of cadaveric livers, split-liver transplantation and living-donor liver transplantation are becoming more common. Preoperative imaging of the donors and recipients are indispensable for surgery planning, while postoperative imaging highly contributes to the success of transplantation by follow-up the transplanted organ and early diagnosis of possible sequelae. The authors delineate both pre- and postoperative imaging of recipients of living-donor transplantation, including the role of conventional x-ray, ultrasound, CT and MRI techniques, and also the different possibilities in the field of interventional radiology.

[Gastrointestinal cytomegalovirus infections in organ transplant patients]. / A gastrointestinalis traktus cytomegalovirus-fertozése szervtranszplantált betegeken.

Cytomegalovirus (CMV) is a major pathogen of immunocompromised organ transplant patients. 80-90% of all transplant patients are infected by the virus; however, the incidence of CMV disease is 30-40%. Gastrointestinal CMV disease occurs in 10% of all transplants involving any part of the gastrointestinal tract. Mucosal injury, ulcerations, erosions, hemorrhage, gastrointestinal dysmotility, rarely gastrointestinal masses, perforations are the most common pathological findings of the CMV disease. The method of specific diagnostics is endoscopy with mucosal biopsy. The biopsy samples must be investigated histopathologically for specific cytomegalic cells with intranuclear ("owl's eye") and intracytoplasmatic inclusions. Different microbiological, immunohistochemical and molecular biological assays can be performed to detect CMV in the mucosa. In case of gastrointestinal CMV disease, both gastroenterological and antiviral treatment are needed by ganciclovir i.v. and/or valganciclovir orally. The prevention of the disease should be achieved by general prophylaxis in high-risk patients (oral valganciclovir, in special cases hyperimmune globulin), and by preemptive therapy using microbiological surveillance in middle-risk patients.

[The role of imaging methods in the pre- and intra-operative evaluation, and in post-operative follow-up of living donors in liver transplantation in Hungary]. / A képalkotó módszerek szerepe az élô donoros májtranszplantáció donorjelöltjeinek pre- és intraoperatív vizsgálatában, valamint posztoperatív követésében Magyarországon.

The evaluation protocol for liver donors can vary from centre to centre, but the main points are the same. Medical history, physical examination, common laboratory tests and psychosocial evaluation are followed by imaging, and specific haemostasis and viral serology tests. The first imaging examinations have the aim of excluding any disease; conventional chest radiography and abdominal ultrasound are performed. Liver volume, fat content, and vascular and biliary anatomy are then evaluated with contrast-enhanced, multiphase, multidetector row CT/CTA and MR cholangiography. Ultrasound guided liver biopsy, and in some cases digital subtraction angiography, should also be performed. During the first phase of the donor operation, intraoperative investigations are done: cholangiography for the final evaluation of the biliary tree and ultrasound of the hepatic and portal venous system to help draw the resection plane. Donors have regular imaging examinations in the early postoperative period for early detection of complications: mainly US or CT to check the remnant hepatic vascularisation and fluid collections in the operated area, or X-ray for thoracic disorders. It is recommended that regular checkups are performed in the late postoperative period. The paper describes the imaging protocol for donor evaluation applied at our institute at the beginning of our living related liver transplantation programme.

[Cytomegalovirus infection after solid-organ transplantation, its risk factors, direct and indirect effects and prevention strategies]. / A cytomegalovírus-fertozés rizikófaktorai, hatásai és a megelozés lehetoségei transzplantációt követoen.

The human cytomegalovirus is widely prevalent among human population and it is the most common viral pathogen that affects both the graft's and solid-organ transplant recipient's survival. The risk is highest in donor-seropositive, recipient-seronegative pairing transplantation. These recipients carry increased risk of developing symptomatic primary CMV infection; however, other risk factors may have an impact on cytomegalovirus activation as well: intensity of immunosuppression, type of organ transplanted, rejection and/or treatment for rejection, HLA-mismatch between recipient and donor, certain HLA-types of the recipient, female sex etc. Cytomegalovirus infection in transplant patients has been associated with both direct (symptoms) and indirect effects which are derived from the immunomodulating impact of the virus such as cellular effects and cytokine expression or systemic immune suppression leading to other opportunistic infections. Prevention of the direct and indirect effects of cytomegalovirus infection is the therapeutic goal in transplanted patients. Most transplant centers use either universal prophylaxis or preemptive therapy to prevent the infection. The advantages and disadvantages of these two preventive strategies and current evidence-based recommendations for preventing cytomegalovirus disease in solid-organ transplant recipients are discussed according to others' and the authors' own observations. According to recommendations of the American and Canadian Societies of Transplantation, most of the centers--after analyzing of the CMV-infection risk factors of the recipients--divide them into three groups: high-, moderate- and low-risk groups. The preventive strategy is attached to the risk-group type. In the high-risk group (R-/D+ and lung transplant patients) the use of the universal prophylaxis is necessary. The patients administered anti-lymphocyte antibodies (ATG, ALG or OKT3) need selective (subtype of universal) prophylaxis. Among the moderate-risk patients (R+/D+ or R+/D-) the doctors may choose either universal prophylaxis or preemptive therapy. Selection of a strategy requires consideration of patient-specific factors as well as practical considerations such as available resources. For avoidance of the indirect effects of CMV infection universal prophylaxis is preferred. The use of preventive proceedings in low-risk patients is the matter of the center's decision.

[Investigation of redox homeostasis in liver and renal transplant recipients]. / Redox homeostasis vizsgálata máj- és vesetranszplantáció során.

The time course of free radical reactions is evaluated by the authors. Within pretransplant patients as of their poorly functioning metabolism free radical overproduction may be observed, hence their antioxidant capacity decreases. When the graft is functioning well, the free radical-antioxidant balance of homeostasis is reestablished. During the early postoperative period, when symptoms (acute rejection, infection, acute tubular necrosis, cholestasis) appear, free radical reactions increase. The authors demonstrate, this is strengthened by the fact that the mediator [interleukin-6 (IL-6), C-reactive protein, serum amyloid-A], and enzyme levels that take part in the free radical processes rise. The monitoring of these parameters during the early postoperative period is a good early indicator for acute rejection and for the effect of therapy. During acute rejection just as during infection most of these parameters increased significantly compared to the healthy control. They show the activation of the immune system but they are not useful for differential diagnosis, with the exception of IL-6 which we measured in larger quantities during bacterial infection but not so in acute rejection. For the prediction of early renal graft function we used urinary enzyme levels (dipeptidyl-aminopeptidase, glutathione-S-transferase). Tissue damage is followed by enzyme increasing and antioxidant capacity depletion. With choosing of adequate tests, the perioperative redox homeostasis of the transplanted patients can be monitored and with dosing the antioxidants the uncontrolled forming of reactive oxygen metabolites can also be decreased and checked.

[The first successful combined heart-kidney transplantation in Hungary]. / Az elso sikeres kombinált szív- és veseátültetés Magyarországon.

Combined heart-kidney transplantation has become a new therapeutic solution for patients with coexisting, irreversible heart and kidney failure. Though this combined approach has several theoretical advantages over sequential transplantation, it remains to be established whether it has a jeopardizing impact on patient and graft outcome. The authors report their experience of the first successful combined heart-kidney transplantation in Hungary from a single donor and review the literature in order to clarify this issue. Young male patient candidate for heart transplantation was suffering from concurrent end stage kidney disease. Donor was selected on the basis of weight and size matching, AB0 compatibility and negative T-cell cross-match. The heart was grafted first, and after the hemodynamic stabilization kidney from the same donor was transplanted. The surgical procedure was uneventful. Heart and kidney function recovered quickly, and the patient is doing very well with good cardiac and renal function even a year following the double organ transplantation. The first Hungarian experience showed that combined heart-kidney transplantation is a therapeutic solution for patients with end stage heart and kidney failure. The lower rate of rejection compared to single heart or kidney transplantation, known from the literature as well, supports their current approach to immunosuppression.

[Biliary complications following orthotopic liver transplantation. The Hungarian experience]. / Epeúti szövodmények májtranszplantáció után.

INTRODUCTION: The authors summarize the characteristics of biliary complications following liver transplantation in the Hungarian liver transplant program. Aims were to analyze the frequency and the types of biliary complications as well as their effect on the patient and graft survival. The authors observed the known risk factors in the Hungarian practice, and they also try to find unknown risk factors for biliary complications. They review the therapy of biliary complications. METHOD: In the retrospective study, patients were divided into two groups, with and without biliary complication after liver transplantation. These two groups were compared with many factors, and with the survivals. The biliary complication group was divided into two parts: those who had an early and those with a late biliary complication. These two new groups were also compared with the controls. The results are summarized in tables and statistical figures. Categorical variables are evaluated by chi 2 -test, continuous ones are with Levine Test (for homogenicity of means), Student T test and Mann-Whitney U-test. Cumulative survivals are computed with Kaplan-Meier log rank analysis. RESULTS: Biliary complication appeared in 25% of the patients. The most frequent complications were stenosis (18%), biliary leakage (9%), biliary necrosis (6%), and ischaemic type of biliary lesions (3%). The 5-year survival is worse when biliary complications were diagnosed (55%) than without such a complication (66%). In the biliary complication group the retransplantation rate was higher (15%). The most frequent treatments were interventional radiologic methods (69%), surgical methods (17%), and the ERCP. CONCLUSIONS: The rate of biliary complications met the international reviews. Risk factors for biliary complications were cholangitis, hepatic artery thrombosis and stenosis, high rate of intraoperative blood transfusions, and acute rejection. Biliary complications frequently associated with the initial poor function of the transplanted graft. Early biliary complications have a negative impact on patient survival, while late complications influence a decreased quality of life. Biliary complications were treated mostly by interventional radiologic procedures.

[Surgical aspects of pediatric liver transplantation. Living donor liver transplant program in Hungary]. / A gyermekkori májátültetés sebészeti alapjai. Az élodonor-program elso lépései Magyarországon.

Because of the long waiting time for pediatric liver transplantation, new techniques of liver transplantation were invented. Split and living-donor related liver transplantation are common today and the Kaplan-Meier (3 years) overall survival is over 80%. By splitting the liver, two recipients can be transplanted. In general, the left lobe is used for the pediatric, the right lobe for the adult recipient. There are a lot of combinations depending on the donor and recipient weight. The accepted liver volume is approx. 1% of the recipient body weight. The results of the Hungarian pediatric program improve, 27 transplantations were done using 14 partial liver grafts and living donor program was started. Using strict protocols and improving surgical skills, the overall pediatric survival was over 80% in the last 5 years.

[Subcapsular hematoma and rupture of the liver graft]. / Subcapsularis haematoma és graftruptura májátültetés után.

Subcapsular hematoma and/or rupture of the graft is uncommon but serious complication of liver transplantation. It may develop spontaneously or following parenchymal injuries or percutaneous transhepatic invasive procedures. This report describes three cases of subcapsular hematoma and/or rupture of the graft with different courses among 350 liver transplantations. In the first case, the patient died due to graft rupture caused by a pseudoaneurysm after biopsy. In the second case, a small injury of the donor liver resulted in a deep rupture, which required partial resection of the graft. The patient died in sepsis later. The third patient presented with a large subcapsular haematoma during transplantation, which was successfully treated. The authors' strategies developed intraoperatively for the management of hematomas. These involve opening and removing of the haematoma, haemostasis with Argon coagulation, which resulted in an adherent Glisson's capsule to the parenchyma and covering with collagen fleece coated with fibrinogen and thrombin.

Antiproliferative and apoptotic effects of mycophenolic acid in human B-cell non-Hodgkin lymphomas.

Mycophenolic acid (MPA)/mycophenolate mofetil (MMF), a powerful immunosuppressive agent was tested on human B-lymphoma cells (Epstein-Barr virus +/-) in vitro and in SCID mouse xenograft model. Proliferation, apoptotic activity and tumor volume were evaluated. MPA inhibited lymphoma cell proliferation and induced apoptosis (50-60% at 72 h). In vivo, oral administration significantly inhibited subcutaneous tumor growth. Immunohistochemistry showed significantly decreased proliferation rate and higher apoptotic activity in tumors treated with MMF. Xenografted lymphoma cells remained sensitive to MPA. Our results suggest that MPA may be recommended as an additional component of lymphoma chemotherapeutical regimens, with special considerations to post-transplant lymphomas.

Malignancies after renal transplantation during 33 years at a single center.

This study provides an analysis of incidence and characteristics of malignant tumors of 2535 patients who underwent renal transplantation between 1973 and 2007 at the Transplantation Center in Budapest. One hundred ninety-three malignant diseases were found in 188 patients (7.6%). The incidence of thyroid-, renal- hepatic-, skin- and gastric cancers as well as of Kaposi sarcoma and lymphomas increased in our transplant patient cohort compared to the figures of the general population based on the data of our Cancer Registry. On the other hand, colorectal-, oralprostate and lung cancers were underrepresented in our patient cohort. The mean time of diagnosis of malignancies following kidney transplantation was 58.5+/-44.8 months. One fifth of the tumors were detected within the first year. Patients with malignancies were distributed into four groups based on the immunosuppressive regimen: group I (8.5%), azathioprine + prednisone; group II (59.0%), cyclosporine + prednisone; group III (26.6%), cyclosporine + mycophenolate mofetil + prednisone; group IV (5.9%), tacrolimus + mycophenolate mofetil + prednisone. The mean age of patients was 47.3, 53.5, 55.5 and 58.1 years in group I, II, III and IV, respectively. Oncologic and immunosuppressive therapy was decided individually. Immunosuppression was switched to rapamycin-containing regimens in 63 cases. We lost 92 patients (48.9%) with a mean survival time of 25.8+/-39.4 months. Cumulative 1- and 5-year survivals were 69.5% and 52%, respectively. The increasing number of cancers seen early after transplantation and the increased risk of developing a cancer due to the older age of recipients draw attention to the importance of regular oncologic screening in patients on the waiting list and after transplantation.

[Malignant tumors following renal transplantation]. / A veseátültetést követoen kialakuló rosszindulatú daganatok.

Patient survival time following renal and other solid organ transplantation has been increasing recently, in part due to modern immunosuppressive regimens. However, the probability of malignant tumor formation is also increasing proportionally to survival time, as a side effect of long-term immunosuppression. The primary factor of increased tumor risk is the deficient antitumoral and antiviral function of the immune system. The frequency of posttransplantation tumors is 2 to 4-fold compared to the non-transplanted population, and the distribution of tumor types is also different. The most frequent tumor types--skin cancer, lymphoma, Kaposi's sarcoma, oral cancer, anogenital tumors, etc.--are often associated with oncogenic viruses. Treatment options and the prognosis of posttransplant tumors are worse than in the normal population. The increasing frequency of posttransplantation tumors is an important factor determining the long-term fate of transplant patients. The reduction of carcinogenic agents, the early diagnosis and treatment of tumors and precancerous conditions, low dose immunosuppression and the usage of immunosuppressive agents with an oncologically favorable, anti-proliferative effect will help reduce the risk of posttransplant tumor formation.

[Lymphocele and kidney transplantation]. / Lymphokele és vesetranszplantáció

INTRODUCTION: Lymphocele is a special complication following kidney transplantation. The authors examined the factors associated with an increased occurrence of clinically significant perinephric fluid collections and/or lymphoceles among sirolimus-treated renal transplant recipients. AIM: From the point of view of the lymphocele a comparison was made for the risks and benefits of the conventional and a newer immunosuppressive combination. METHODS: At the University of Texas in Houston in a retrospective study the incidence, predisposing factors, and consequences of these fluid collections among patients treated with sirolimus-cyclosporine-prednisone ( n = 354, Group I) versus cyclosporine-prednisone-azathioprine ( n = 136, Group II) were compared. RESULTS: More Group I patients (135/354; 38.1%) displayed perinephric fluid collections than Group II patients (24/136; 17.6%; p < 0.001). In both subgroups the serum creatinine levels were elevated at the time of diagnosis from a nadir of 179.5 +/- 141.7 to 359.9 +/- 259.6 mmol/l (Group III, sirolimus treated) and from 222.6 +/- 205.9 to 383.7 +/- 255.2 mmol/l (Group IV, sirolimus free). A significantly greater number of patients required treatment for lymphoceles among Group I (15.8%; 56/354) versus Group II recipients (4.4%; 6/136; p < 0.001). Single or repeated percutaneous drainage procedures successfully treated 35 Group I patients versus all 6 Group IV patients ( p = 0.033). No patients in Group II versus 21 patients in Group I underwent surgical procedures ( p < 0.001). A significantly higher rate and higher histologic grade of acute rejection episodes, particularly proximate to the onset of the lymphocele, occurred among Group IV patients, namely 54.2% (13/24) versus 21.4% (29/135) Group III patients ( p < 0.001). Additionally we report the case of a 29-year-old patient who underwent a lymphocele fenestration with omentoplasty 8 years after his transplantation. Despite an Influenza A + Chlamydia pneumonia and acute rejection which was followed by a GI bleeding and stomach resection he fully recovered and is doing well with an excellent kidney function a year after. CONCLUSIONS: Addition of sirolimus to a cyclosporine-prednisone regimen resulted in both a higher incidence and a requirement for more aggressive treatment of perinephric fluid collections and/or lymphoceles with a much lower acute rejection frequency.

[The recurrence of hepatitis C virus after liver transplantation]. / Hepatitis C-vírus kiújulása májátültetés után.

UNLABELLED: The main indication of the Hungarian Liver Transplant Program is liver cirrhosis caused by hepatitis C. AIM: Authors present the results of liver transplantations performed due to HCV infection. METHOD: The data (donor-, recipient-, perioperative characteristics, survival, serum titer of C RNA, histology) of 111 HCV positive recipients were evaluated, that are 37.6% of the 295 patients, who were transplanted since 1995 till the closure of this report. RESULTS: Twenty-two (22) of them (20%) died in the early postoperative period, for other reasons, before the recurrence of the HCV was detectable. Among the 89 HCV-positive patients the recurrence of the HCV is still not detected in 16 cases (18%), and there is a histology-proven recurrence in 73 cases (82%). In 40 cases (56%) the viral recurrence was proven within 1 year after OLT, while in 32 cases (44%) over 1 year. The cumulative 1, 3, 5, and 10 years patient survival is 73%, 67%, 56% and 49%, among HCV-positive patients and 80%, 74%, 70% and 70% among HCV-negatives. The difference is significant. The cumulative graft survival at the same time points is 72%, 66%, 56% and 49% among HCV-positives and 76%, 72%, 68% and 68% among HCV-negatives, which is a non-significant difference. The serum titer of HCV-RNA was significantly higher among those HCV-patients who had an early viral recurrence within 1 year, compared to those who had a late one. In case of an early HCV-recurrence the Knodell-score was significantly higher in the 6 months posttransplant biopsy than that of in case of late viral recurrence, however, less fibrosis was observed in early recurrence. CONCLUSIONS: An early HCV recurrence can be expected in case of an older donor, with a marginal or fatty liver graft transplanted with a higher transfusion need and having an acute rejection treated with steroid bolus in the postoperative period. The protocol of the postoperative antiviral treatment differs from the average: the so-called "stop-rule" cannot be applied, since less then 10% of the recipients are expected to turn to HCV-PCR-negative due to the immunosuppression. The combined interferon + ribavirin treatment is maintained in spite of RNA-positive state, further, a second or third course of treatment might also be applied. The prolonged and--in case if necessary--repeated antiviral treatment prevents fibrosis, and therefore rate of retransplantation need. The better is the general state of the patient the results of a secondary liver transplantation are better as well. MELD-score can help to set the exact timing for a re-OLT.