Zsuzsanna Gerlei

MicroRNA profile before and after antiviral therapy in liver transplant recipients for hepatitis C virus cirrhosis

Management of hepatitis C virus (HCV) recurrence is a major challenge after liver transplantation. Significant dysregulated expression of HCV receptors (i.e. claudin‐1, occludin, tetraspanin CD81, scavenger receptor type B1) has been shown recently during HCV infection. This might facilitate hepatocytic entry and reinfection of HCV. MicroRNAs (miRs) play role in the regulation of gene expression. We aimed to characterize miR expression profiles related to HCV infection and antiviral therapy in adult liver transplant recipients, with special emphasis on miRs predicted to target HCV receptors.

The effect of steroid pretreatment of deceased organ donors on liver allograft function: A blinded randomized placebo-controlled trial

Background & Aims Brain death-associated inflammatory response contributes to increased risk of impaired early liver allograft function, which might be counterbalanced by steroid pretreatment of the organ donor. The aim of this randomized controlled trial was to elucidate whether steroid pretreatment of liver donors improves early liver allograft function, prevents rejection and prolongs survival. Methods A placebo-controlled blinded randomized clinical trial was performed in three different centers in Austria and Hungary between 2006 and 2008. Ninety deceased organ donors received either 1000 mg of methylprednisolone or placebo 6 h before recovery of organs. The primary end point was the concentration slope of transaminases within the first week. The secondary end point included survival and biopsy-confirmed acute rejection (BCAR) within 3 years after transplantation. Results Of the 90 randomized donors, 83 recipients were eligible for study. The trajectories of ALT and AST were not different between treatments (p = 0.40 and p = 0.13, respectively). Eight subjects died in the steroid and 13 in the placebo group within 3 years after engraftment (RR = 0.63 95% CI [0.29, 1.36], p = 0.31). Eleven recipients experienced biopsy-confirmed rejection (BCAR) in the steroid and 11 in the placebo group (RR = 1.02 95% CI [0.50, 2.10], p = 1.00). No effect modification could be identified in the predefined strata of donor age, sex, cold ischemic time, and cause of donor death. Conclusions Steroid pretreatment of organ donors did not improve outcomes after liver transplantation.

Comparing cytomegalovirus prophylaxis in renal transplantation: single center experience

Abstract: Background: Cytomegalovirus (CMV) presents a serious threat to CMV‐seronegative recipients (R−), who have received an organ from a seropositive donor (D+).

H1N1 Vaccination in Pediatric Renal Transplant Patients

BACKGROUND Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population. METHODS In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination. RESULTS None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection. CONCLUSIONS We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients.

Relationship Between Hepatitis C Virus Recurrence and De Novo Diabetes After Liver Transplantation: The Hungarian Experience

De novo diabetes mellitus is a common complication after liver transplantation. It is strongly associated with hepatitis C virus (HCV) infection. We analyzed the relationship between HCV recurrence and de novo diabetes among the Hungarian liver transplant population. This retrospective study included cases from 1995 to 2009 on 310 whole liver transplantations. De novo diabetes was defined if the patient had a fasting plasma glucose ≥126 mg/dL permanently after the third month post liver transplantation, and/or required sustained antidiabetic therapy. De novo diabetes occured in 63 patients (20%). The cumulative patient survival rates at 1, 3, 5, and 8 years were 95%, 91%, 88%, and 88% in the control group, and 87%, 79%, 79%, and 64% in the de novo group, respectively (P=.011). The majority of the patients in the de novo group were HCV positive (66% vs 23%). Early virus recurrence within 5 months was associated with the development of diabetes (80% vs 20% non-diabetic controls; P=.017). The fibrosis (2.05 ± 1.5 vs 1 ± 1; P=.039) and Knodell scores (3.25 ± 2 vs 1.69 ± 1.2; P=.019) were higher among the de novo group after antiviral therapy. Rapid recurrence, more severe viremia, and fibrosis showed significant roles in the developement of de novo diabetes after liver transplantation.

New-onset diabetes mellitus after liver transplantation

A de novo diabetes mellitus a majatultetes gyakori szovődmenye. Celkitűzes: A de novo diabetes gyakorisagat, jelentőseget es a kockazati tenyezők szerepet vizsgaltuk. Modszer: 1995 es 2009 kozott 310 majatultetett beteg adatait dolgoztuk fel retrospektiv modszerrel. De novo diabetest allapitottunk meg, ha az ehomi vercukor a 3. posztoperativ honapon tul ismetelten >6,8 mmol/l volt, es/vagy a majatultetes utan tartos, a 3. posztoperativ honapot meghaladoan is fenntartott antidiabetikus terapia indult. Eredmenyek: De novo diabetes a betegek 20%-anal (63 beteg) alakult ki. A de novo es a kontrollcsoport kozott az alabbiakban talaltunk kulonbseget. Donor-testtomegindex (24±3 vs. 22,4±3,6 kg/m 2 , p = 0,003), ferfi nem (58% vs. 33%, p = 0,002). Recipienseletkor (47,6±7,2 vs. 38,3±14,6 ev, p<0,001), -testtomegindex (26,7±3,8 vs. 23,3±5,6 kg/m 2 , p<0,001), ferfi nem (60% vs. 44%, p = 0,031). A de novo diabetesesek csoportjaban a betegek 66%-at HCV talajan kialakult cirrhosis miatt transzplantaltak, a kontrollcs...UNLABELLED New-onset diabetes is a common complication after liver transplantation. AIM We aimed to analyze the incidence and rate of known risk factors and the impact of new-onset diabetes mellitus on postoperative outcome. METHODS We retrospectively evaluated the files of 310 patients who underwent liver transplantation between 1995 and 2009. Definition of new-onset diabetes included: repeated fasting serum glucose >6.8 mmol/l and/or sustained antidiabetic therapy that was present 3 months after transplantation. RESULTS New-onset diabetes occurred in 63 patients (20%). Differences between the new-onset and the control group were the donor body mass index (24+/-3 vs. 22.4+/-3.6 kg/m 2 , p = 0.003), donor male gender (58% vs. 33%, p = 0.002), and recipient age (47.6+/-7.2 vs. 38.3+/-14.6 year, p<0.001), body mass index (26.7+/-3.8 vs. 23.3+/-5.6 kg/m 2 , p<0.001), male gender (60% vs. 44%, p = 0.031). The 66% of patients with new-onset diabetes were transplanted with cirrhosis caused by hepatitis C virus infection, while in the control group the rate was 23% (p<0.001). Cumulative patient survival rates at 1, 3, 5 and 8 year were 95%, 90.6%, 88% and 88% in the control group, and 87%, 79%, 79% and 64% in the de novo group, respectively (p = 0.011). Cumulative graft survival rates at 1, 3, 5 and 8 year in the control group were 92%, 87%, 86% and 79%, in the de novo diabetes group the rates were 87%, 79%, 79%, 65%, respectively (p = NS). In case of early recurrence (in 6 months), majority of patients developed new-onset diabetes (74% vs. control 26%, p = 0.03). More patients had more than 10 times higher increase of the postoperative virus titer correlate to the preoperative titer in the de novo diabetes group (53% vs. 20%, p = 0.028). Mean fibrosis score was higher in new-onset group one year after the beginning of antiviral therapy (2.05+/-1.53 vs. 1.00+/-1.08, p = 0.039). CONCLUSIONS Risk factors for new-onset diabetes after transplantation are older age, obesity, male gender and cirrhosis due to hepatitis C infection. The early recurrence, viremia and more severe fibrosis after antiviral therapy have an impact on the occurrence of new-onset diabetes in hepatitis C positive patients.

Hepatic steatosis in individuals living with HIV measured by controlled attenuation parameter: a cross-sectional study.

Objectives Available data on the prevalence of hepatic steatosis in an unselected HIV-infected population are limited. The aim of this study was to determine the prevalence of hepatic steatosis and assess the associated factors in HIV-infected individuals. Patients and methods One hundred and thirty-six HIV-infected individuals were enrolled in this cross-sectional study. Patients underwent transient elastography and controlled attenuation parameter (CAP) measurements. We analyzed the associations between the CAP value and demographic, metabolic, and immunologic parameters. For the first time, in HIV-infected individuals, we used a continuous scale of CAP values to identify significant covariates of hepatic fat accumulation. As a result and compared with other methods, one of the main advantages of CAP was that the quantitative measurement of liver steatosis could be used for analysis. Results Using univariate analysis, CAP was significantly correlated with the following continuous variables: CD4 percentage (P=0.035), CD8 percentage (P=0.016), age (P<0.001), CD4/8 ratio (P=0.002), BMI (P<0.001), serum triglyceride (P<0.001), and serum cholesterol (P=0.004) levels, the length of known HIV positivity (P<0.001), and liver stiffness (P=0.041). With respect to categorical variables, a significant association was found for the presence of diabetes (P=0.006), hypertension (P<0.001), facial lipodystrophy (P=0.031), and the use of lopinavir (P=0.042). In multivariate analysis using linear regression, BMI (P<0.001), presence of diabetes (P=0.026), and hypertension (P=0.040) were identified as independent significant correlates. Darunavir therapy was associated negatively with the CAP value (P=0.032). Conclusion Our findings reflect the importance of metabolic factors in hepatic steatosis. The strongest independent covariate was BMI.

Surgical aspects of pediatric liver transplantation. Living donor liver transplant program in Hungary

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.

Childbirth After Organ Transplantation in Hungary

BACKGROUND The first successfully delivered newborn after organ transplantation was reported in 1963; since then, >14,000 women have delivered after transplantation. Patients with an end-stage organ disease develop fertility disturbances. One year after a successful solid organ transplantation with stable graft function, fertile women can give birth to a child from a medical point of view. Pregnant transplant patients do experience a high risk of graft function worsening, a rejection episode, and opportunistic infections. Furthermore, the medical therapy may influence teratogenicity. METHODS Between 1974 and September 1, 2010, 5 Hungarian centers performed 6802 solid organ transplantation and lungs were grafted in Vienna, Austria. The organ distribution was: 5971 kidney, 454 liver, 187 heart, 90 combined pancreas-kidney, 5 combined islet-kidney, and 95 lung transplantation. There were no pregnancies among heart, lung, and pancreas recipients. RESULTS In all, 3.9% of the renal and 14.3% of the fertile liver transplanted women gave birth to children. To wit, 23 kidney recipients delivered 27 healthy children (17 boys and 10 girls). In 4 cases, 2 children were born, twice as twins. Among liver recipients, 8 women delivered 8 healthy babies. There was no hepatitis C or B virus-positive patient among the mothers. There was no graft insufficiency, rejection or birth defect. Transplanted mothers often display toxemia or preeclampsia during pregnancy requiring cesarean section. The relatively higher ratio of liver recipients was perhaps due to the rarer occurrence of extrahepatic organ damage, like diabetic nephropathy or cardiomyopathy, and the reversible nature of hepatorenal or hepatopulmonary syndrome. CONCLUSION Delivery of a child by a transplanted mother carries an high risk, requiring interdisciplinary cooperation. The quality of life of solid organ recipients can be significantly raised by childbirth under appropriate circumstances.

Recurrence of primary sclerosing cholangitis after liver transplantation - The Hungarian experience.

INTRODUCTION Recurrence of primary sclerosing cholangitis (rPSC) after liver transplantation (OLT) significantly affects long-term graft survival. We aimed to evaluate the incidence of rPSC and clinical data of these patients in Hungary. PATIENTS AND METHODS We retrospectively analyzed data of 511 whole liver transplantations from 1995 to 2011. During the study period, 49 OLTs were performed in 43 adult patients with end-stage PSC (10%). RESULTS Out of 49 OLT, 24 cases were excluded, rPSC was diagnosed in six patients (12%). Patients with rPSC had significantly higher mortality (p = 0.009) and graft loss (p = 0.009) in comparison to patients without recurrent disease. Younger recipient age, higher donor BMI was observed in the rPSC group. One patient was diagnosed with de novo IBD, the remaining five patients had worsening IBD activity in the posttransplant period. PreOLT colectomy was performed in 21% of the control and none of the rPSC group. PostOLT colectomy was performed in two rPSC patients due to severe therapy resistant colitis. CONCLUSIONS Recurrent PSC significantly affects long-term mortality and graft loss. Younger age at OLT, higher donor BMI and severe active IBD may be associated with PSC recurrence. PreOLT total colectomy might have protective effect against rPSC.