Long-term Liver Transplant Recipients Research Articles

Conversion from twice-daily everolimus to once-daily sirolimus in long-term stable liver transplant recipients

BackgroundAfter organ transplantation, strategies for simplifying the therapeutic regimen may improve adherence and prevent acute organ rejection and/or late graft loss. The present study aimed to evaluate the safety and efficacy of conversion from everolimus (EVR) twice daily to sirolimus (SIR) once daily in a large cohort of liver transplantation (LT) patients. MethodsWe included 108 LT patients with at least 12 months of post-transplant follow-up and no rejection episodes in the last year. Conversion was based on a 1:1 ratio (but eventually adapted to available formulations of SIR). ResultsThe median age at the time of conversion was 68.9 years (range: 26.1–83.6); 75.0% were men. The main indications for mTOR inhibitor use were renal failure (38.9%) and/or a history of malignancy (37.0%). Median conversion time after LT was 14.8 years (range: 2.3–31.5). The median dose of EVR and SIR (initially) was 1.50 mg/day (range: 0.5–4.5). The mean follow-up after conversion was 15.8±4.4 months. Median serum EVR/SIR trough levels before/after conversion were 3.85 ng/mL vs. 6.32 ng/mL (p < 0.05), i.e. a 1:1.64 ratio. At the end of follow-up after conversion, the median dose of SIR was 1.25 mg/day (range: 0.5–3.5), and the mean serum SIR trough level was 5.23 ng/mL; 9 patients (8.3%) had returned to EVR, because of side effects (mainly digestive), that resolved thereafter. No biopsy-proven acute rejection episode was observed. Finally, 87.1% of patients considered the conversion beneficial and the cost was reduced by 50.3%. ConclusionThe results of our study indicate that conversion from once-daily EVR to once-daily SIR in stable LT patients is safe, but needs dose adaptations and careful monitoring.

Association of torque teno virus viremia with liver fibrosis in the first year after liver transplantation.

Torque teno virus (TTV) replication is controlled by immune status, mirroring a degree of immunosuppression after solid organ transplantation. TTV viraemia (TTVv) was associated with acute cellular rejection and infection within the first year after liver transplantation (LT). Long-term data on TTV after LT and correlation with graft injury from protocol biopsies are limited. One hundred plasma samples paired with graft biopsies from a prospective single-center biorepository were analyzed. The median time post-LT was 23 months (range, 2-298). TTVv was detectable in 97%. TTVv decreased over time after LT and showed a significant decline from year 1 to later time points. Hence, TTVv correlated negatively with histologic liver fibrosis (liver allograft fibrosis and Ishak scores) and positively with the overall immunosuppression degree quantified by an immunosuppression score in the first year after LT. There was no association with dosages or trough levels of single immunosuppressants. The pharmacodynamic marker TTVv did not correlate with pharmacokinetic assessments of immunosuppression degree [calcineurin inhibitor (CNI) trough levels or immunosuppressant dosages]-our clinical gold standards to guide immunosuppressive therapy. TTVv was independently associated with histologically proven liver fibrosis after LT in the first year after LT in multivariate analysis. The independent association of histological graft fibrosis with lower TTVv in year 1 underscores that a pharmacodynamic marker would be preferable to individualize immunosuppression after LT. However, a high variability of TTVv at the low immunosuppression doses given after the first year precludes TTV as a clinically useful marker after LT in the long-term liver transplant recipients.

Pancreatic adenocarcinoma in liver transplant recipients: a case series.

Background:Malignancy is one of the known leading causes of death among long-term liver transplantation (LT) survivors. Pancreatic cancer has an incidence of 7.6/100,000 in North America and constitutes a diagnostic challenge post-LT.Methods:This is a single-center, retrospective review of the electronic health records (EHRs) of LT recipients with pancreatic adenocarcinoma (1990–2019). The prevalence of pancreatic adenocarcinoma in our institutional non-LT population was assessed using an institutional de-identified database (Synthetic Derivative).Results:Six out of 2,232 (0.27%) LT recipients were diagnosed with pancreatic adenocarcinoma. Median age at diagnosis was 66.0 years (IQR, 57.8–71.8 years). Median time from LT to pancreatic adenocarcinoma diagnosis was 8.9 years (IQR, 4.7–16.2 years), the median size on imaging was 3.2 cm (IQR, 3.1–4.7 cm), and all tumors were located on the head of the pancreas. Three patients underwent surgical resection (one with adjuvant chemotherapy), two underwent palliative care, and one palliative chemotherapy with gemcitabine and abraxane. Over a median follow-up of 220.5 days (IQR, 144.8–399.5 days), all six patients died due to disease progression (100%). Pancreatic adenocarcinoma was diagnosed in 5,033 out of 2,484,772 (0.20%) individuals in the Synthetic Derivative.Conclusions:Our findings identified an increased incidence of pancreatic adenocarcinoma following LT compared to the general population.

Outcome of Corona Virus Disease (COVID-19) in Egyptian Cohort of Long-Term Liver Transplant Recipients: Single Center Experience

Among 21 cases of COVID-19 infection in our center, median age at diagnosis was 40 ± 12.8 years, and the median interval since transplantation was 4.75 years. Fever (100%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (80%) were the most common presentations. Macrolide's antibiotics were used in 75% of patient.95% was improved and 4.6% showed mortality, reduction or stoppage of current immunosuppressives were only in 19%.

Non-invasive alloimmune risk stratification of long-term liver transplant recipients

Management of long-term immunosuppression following liver transplantation (LT) remains empirical. Surveillance liver biopsies in combination with transcriptional profiling could overcome this challenge by identifying recipients with active alloimmune-mediated liver damage despite normal liver tests, but this approach lacks applicability. Our aim was to investigate the utility of non-invasive tools for the stratification of stable long-term survivors of LT, according to their immunological risk and need for immunosuppression. We conducted a cross-sectional multicentre study of 190 adult LT recipients assessed to determine their eligibility to participate in an immunosuppression withdrawal trial. Patients had stable liver allograft function and had been transplanted for non-autoimmune non-replicative viral liver disease >3 years before inclusion. We performed histological, immunogenetic and serological studies and measured the intrahepatic transcript levels of an 11-gene classifier highly specific for T cell-mediated rejection (TCMR). In this cohort, 35.8% of patients harboured clinically silent fibro-inflammatory liver lesions (13.7% had mild damage and 22.1% had moderate-to-severe damage). The severity of liver allograft damage was positively associated with TCMR-related transcripts, class II donor-specific antibodies (DSAs), ALT, AST, and liver stiffness measurement (LSM), and negatively correlated with serum creatinine and tacrolimus trough levels. Liver biopsies were stratified according to their TCMR transcript levels using a cut-off derived from biopsies with clinically significant TCMR. Two multivariable prediction models, integrating ALT+LSM or ALT+class II DSAs, had a high discriminative capacity for classifying patients with or without alloimmune damage. The latter model performed well in an independent cohort of 156 liver biopsies obtained from paediatric liver recipients with similar inclusion/exclusion criteria. ALT, class II DSAs and LSM are valuable tools to non-invasively identify stable LT recipients without significant underlying alloimmunity who could benefit from minimisation of immunosuppression. A large proportion of liver transplant patients with normal liver tests have inflammatory liver lesions, which in 17% of cases are molecularly indistinguishable from those seen at the time of rejection. ALT, class II donor-specific antibodies and liver stiffness are useful in identifying patients with this form of subclinical rejection. We propose these markers as a useful tool to help clinicians determine if the immunosuppression administered is adequate.

Efficacy and Safety of Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients: Moving Toward Personalized Management.

Tolerance is transplantation's holy grail, as it denotes allograft health without immunosuppression and its toxicities. Our aim was to determine, among stable long-term pediatric liver transplant recipients, the efficacy and safety of immunosuppression withdrawal to identify operational tolerance. We conducted a multicenter, single-arm trial of immunosuppression withdrawal over 36-48weeks. Liver tests were monitored biweekly (year 1), monthly (year 2), and bimonthly (years 3-4). For-cause biopsies were done at investigators' discretion but mandated when alanine aminotransferase or gamma glutamyltransferase exceeded 100U/L. All subjects underwent final liver biopsy at trial end. The primary efficacy endpoint was operational tolerance, defined by strict biochemical and histological criteria 1year after stopping immunosuppression. Among 88 subjects (median age 11years; 39 boys; 57 deceased donor grafts), 33 (37.5%; 95% confidence interval [CI] 27.4%, 48.5%) were operationally tolerant, 16 were nontolerant by histology (met biochemical but failed histological criteria), and 39 were nontolerant by rejection. Rejection, predicted by subtle liver inflammation in trial entry biopsies, typically (n=32) occurred at ≤32% of the trial-entry immunosuppression dose and was treated with corticosteroids (n=32) and/or tacrolimus (n=38) with resolution (liver tests within 1.5 times the baseline) for all but 1 subject. No death, graft loss, or chronic, severe, or refractory rejection occurred. Neither fibrosis stage nor the expression level of a rejection gene set increased over 4years for either tolerant or nontolerant subjects. Immunosuppression withdrawal showed that 37.5% of selected pediatric liver-transplant recipients were operationally tolerant. Allograft histology did not deteriorate for either tolerant or nontolerant subjects. The timing and reversibility of failed withdrawal justifies future trials exploring the efficacy, safety, and potential benefits of immunosuppression minimization.

Protocol liver biopsies in stable long-term pediatric liver transplant recipients: risk or benefit?

Follow-up after pediatric liver transplantation (LTX) is challenging and needs to be refined to extend graft survival as well as general functional health and patients´ quality of life. Strategies towards individual immunosuppressive therapy seem to play a key role. Our aim was to evaluate protocol liver biopsies (PLB) as a tool in personalized follow up after pediatric LTX. Our retrospective analysis evaluates 92 PLB in clinically asymptomatic pediatric patients after LTX between 2009 and 2019. Histological findings were characterized using the Desmet scoring system. In addition to PLB, other follow-up tools like laboratory parameters, ultrasound imaging and transient elastography were evaluated. Risk factors for development of fibrosis or inflammation were analyzed. PLB revealed a high prevalence of graft fibrosis (67.4%) and graft inflammation (47.8%). Graft inflammation was significantly (P = 0.0353*) more frequent within the first 5 years after transplantation compared to later time points. Besides conventional ultrasound, the measurement of liver stiffness using transient elastography correlate with stage of fibrosis (r = 0.567, P = <0.0001***). Presence of donor-specific anti-human leukocyte antigen antibodies in blood correlates with grade of inflammation in PLB (r = 0.6040, P = 0.0018 **). None of the patients who underwent PLB suffered from intervention-related complications. Histopathological results had an impact on clinical decision making in one-third of all patients after PLB. PLB are a safe and useful tool to detect silent immune-mediated allograft injuries in the context of normal liver parameters.

Coronavirus Disease 2019 in Recipient of Allogeneic Hematopoietic Stem Cell Transplantation: Life-threating Features Within the Early Post-engraftment Phase.

Coronavirus Disease 2019 in Recipient of Allogeneic Hematopoietic Stem Cell Transplantation: Life-threating Features Within the Early Post-engraftment Phase.

Interferon-free Anti-hepatitis C Virus Treatment for Long-term Liver Transplantation Recipients with Failed Interferon Therapy

Interferon-free Anti-hepatitis C Virus Treatment for Long-term Liver Transplantation Recipients with Failed Interferon Therapy

Solid-organ transplant surgeries in era of COVID-19 pandemic: How to go about it?

Solid-organ transplant surgeries in era of COVID-19 pandemic: How to go about it?

Torque Teno Virus Is Associated With the State of Immune Suppression Early After Liver Transplantation.

The development of noninvasive biomarkers that reflect the state of immunosuppression (IS) remains an unmet need in liver transplantation (LT). Torque Teno virus (TTV) is a highly prevalent, nonpathogenic DNA virus whose plasma levels may be associated with the immune status of the host. The aim of this study was to assess the role of TTV as a biomarker of IS in LT recipients. TTV DNA in plasma was quantified by real-time polymerase chain reaction at different time points during the first year after transplant in a prospectively followed cohort of 63 de novo LT recipients, and any correlation between TTV DNA and biopsy-proven acute cellular rejection (ACR) and opportunistic infections was then evaluated. In addition, TTV DNA was studied in 10 longterm LT recipients in monotherapy with tacrolimus, 10 tolerant recipients, and 10 healthy controls. TTV was detected in the plasma of all patients. Among the 63 LT recipients, 20 episodes of ACR were diagnosed, and there were 28 opportunistic infections, 26 of them being cytomegalovirus (CMV) infections. TTV viremia was significantly lower during ACR (4.41 versus 5.95 log10 copies/mL; P = 0.002) and significantly higher during CMV infections (5.79 versus 6.59 log10 copies/mL; P = 0.009). The area under the receiver operating characteristic curve of TTV viral load for the diagnosis of moderate ACR was 0.869, with a sensitivity and negative predictive value of 100%, respectively, for a cutoff point of 4.75 log10 copies/mL. There were no statistically significant differences in TTV DNA in either longterm or tolerant patients and healthy controls. In conclusion, plasma TTV DNA levels are associated with immune-related events after LT and could constitute a potential biomarker of the state of IS during the first months after transplant.

PS-047 - Prevalence of subclinical histological lesions and tolerance biomarkers in long-term adult liver transplant recipients considered for immunosuppression withdrawal

PS-047 - Prevalence of subclinical histological lesions and tolerance biomarkers in long-term adult liver transplant recipients considered for immunosuppression withdrawal

Immunosuppression Practices in Liver Transplantation: A Survey of North American Centers.

There is a clear lack of clinical evidence guiding immunosuppressive management in long-term stable liver transplant recipients. As a result, anecdotal experience suggests wide variability across transplant centers. We aimed to identify patterns of immunosuppression practices in liver transplant centers across Canada and the United States. From February 9 to May 31, 2015, we invited clinicians from all liver transplant centers in Canada and the United States to answer a 6-question survey generated using SurveyMonkey. Seventeen respondents from 15 liver transplant centers completed the survey. Although immun-suppressive practices are relatively uniform for induction and early maintenance therapy, significant variations exist in the management of long-term immunosuppression in stable transplant recipients with a relative lack of minimization protocols. Our survey confirms a wide variability in immunosuppression practices across Canadian and US liver transplant centers. Research and practice priorities include design of pragmatic randomized controlled trials and development of clinical practice guidelines to standardize immunosuppressive management of long-term stable liver transplant recipients with a focus on immunosuppression minimization.

Real-World Multicenter Experience of Immunosuppression Minimization Among 661 Liver Transplant Recipients.

BackgroundLong-term morbidity and mortality in liver transplant recipients is frequently secondary to immunosuppression toxicity. However, data are scarce regarding immunosuppression minimization in clinical practice.Material/MethodsIn this cross-sectional, multicenter study, we reviewed the indications of immunosuppression minimization (defined as tacrolimus levels below 5 ng/mL or cyclosporine levels below 50 ng/mL) among 661 liver transplant recipients, as well as associated factors and the effect on renal function.ResultsFifty-three percent of the patients received minimized immunosuppression. The median time from transplantation to minimization was 32 months. The most frequent indications were renal insufficiency (49%), cardiovascular risk (19%), de novo malignancy (8%), and cardiovascular disease (7%). The factors associated with minimization were older age at transplantation, longer post-transplant follow-up, pre-transplant diabetes mellitus and renal dysfunction, and the hospital where the patients were being followed. The patients who were minimized because of renal insufficiency had a significant improvement in renal function (decrease of the median serum creatinine level, from 1.50 to 1.34 mg/dL; P=0.004). Renal function significantly improved in patients minimized for other indications, too. In the long term, glomerular filtration rate significantly decreased in non-minimized patients and remained stable in minimized patients.ConclusionsImmunosuppression minimization is frequently undertaken in long-term liver transplant recipients, mainly for renal insufficiency. Substantial variability exists regarding the use of IS minimization among centers.

Evaluation of Immune Profiles and MicroRNA Expression Profiles in Peripheral Blood Mononuclear Cells of Long-Term Stable Liver Transplant Recipients and Recipients With Acute Rejection Episodes

ObjectiveThis study aimed to document the difference of immunophenotypes in peripheral blood mononuclear cells (PBMCs) between long-term stable liver transplant recipients and recipients with acute rejection. We also sought to identify whether there is any correlation between microRNA (miRNA) expression profile and the differential immunoprofile in these 2 groups to establish a specific miRNA biomarker to identify potential liver transplant recipients. MethodsPBMCs were isolated from 53 stable liver transplant recipients (STA group) and 15 liver transplant recipients with repeated biopsy-proven rejection episodes admitted to our hospital. Immunoprofiles were analyzed by means of flow cytometry. Analysis of miRNA expression in the PBMCs was performed by means of real-time polymerase chain reaction. ResultsThe immune profiling analysis showed increased frequency of peripheral natural killer cells and regulatory T cells in stable liver transplant recipients compared with the acute rejection recipients and healthy volunteers (P < .05). There was no significant difference in the immune cell levels (CD19+ B cells, CD4+ T cells, and CD8+ T cells) in PBMCs among the transplant recipient groups and healthy control subjects. Three miRNAs, miR-18b, miR-340, and miR-106b, were up-regulated in the PBMCs of the STA recipients compared with recipients with acute rejection. ConclusionsThese results suggest that miR-18b, miR-340, and miR-106b, which regulate the expression of specific immunophenotypes, can be used as potential biomarkers to identify long-term stable liver transplant recipients from recipients with acute rejection.

Telbivudine in liver transplant recipients: Renal protection does not overcome the risk of polyneuropathy and myopathy.

The recently reported benefit of telbivudine for renal function has not been systematically studied in long-term liver transplantation (LT) recipients who are at high risk for renal impairment. We aimed to examine whether switching lamivudine therapy to telbivudine could improve renal function in LT recipients who have impaired renal function. This single-center, prospective cohort study enrolled LT recipients who were on lamivudine for hepatitis B virus (HBV) prophylaxis and who had renal impairment for at least 1 year. Lamivudine was switched to telbivudine. The primary outcome was to evaluate the change in renal function at weeks 12, 24, 36, and 48. The secondary outcomes were to assess the efficacy of telbivudine for HBV prophylaxis and the safety profile of telbivudine in the posttransplant setting. After 45 patients were enrolled, the study was terminated early because of increased rates of polyneuropathy/myopathy. During telbivudine treatment (median, 64 weeks), estimated glomerular filtration rate (eGFR) increased in 34 patients (76%). The improvement in renal function was prominent after 24 weeks of telbivudine treatment. Telbivudine was effective as prophylaxis against HBV recurrence. Twenty-six patients (58%) developed polyneuropathy and/or myopathy. The 1-year estimated incidence of polyneuropathy/myopathy was 28%. Diabetes was the strongest predictor of polyneuropathy/myopathy (hazard ratio, 4.13; 95% confidence interval, 1.49-11.50; P = 0.007). In conclusion, although it seems to have a favorable effect in the improvement of renal function and seems to be effective in the prevention of HBV recurrence, the high risk of polyneuropathy and myopathy hampers the use of telbivudine in LT recipients.

Structural Clustering With Clinical Correlates in Stable Long-Term Pediatric Liver Transplant Recipients With Normal Liver Tests: A Prospective Multi-Center Study.

Background: Single center retrospective studies report variable inflammation and progressive fibrosis in long-term pediatric liver allografts. We rigorously describe and analyze structural changes in liver allografts in a multi-center cohort of stable children with ALT and GGT <50IU/L. Methods: Screening, pre-weaning liver biopsies (bxs) done at 12 North American centers in an immunosuppression withdrawal study for children ≥4ys post-transplant (tx) were scored by a central pathologist for 48 histologic criteria. Hierarchial cluster analysis was performed on 3 dominant features: 1)periportal/portal fibrosis 2)perivenular fibrosis 3)interface activity (IA). Multivariable logistic regression analysis with clinical covariates and backward variable selection (p<0.10 for retention) identified independent predictors of cluster assignment. Results: 100 recipients (47M/53F) of living (30)/deceased (70; 48 whole; 22 partial) donor tx at 1.9±1.7ys underwent bx at 11.5±3.3ys, 9.7±3.2ys after tx when ALT and GGT were 27±9 and 17±7IU/L. Bxs segregated into 3 distinct clusters (Figure): 1 no fibrosis no IA (n=52); 2 fibrosis but no IA (n=32); 3 IA +/- fibrosis (n=16). Increased age at bx predicted cluster 2 (fibrosis) while higher ALT predicted cluster 3 (IA) (Table). Age at tx, time since tx, donor age, living vs deceased donor, whole vs partial graft, and rejection history did not predict cluster assignment. Conclusions: Long-term pediatric liver tx recipients with normal liver tests can harbor significant structural changes with/without inflammation. Distinct structural clusters and their clinical correlates suggest both non-immune and immune mechanisms of histologic allograft deterioration. Future data, including C4d score, donor specific antibody, and tolerant/non-tolerant phenotype may confirm the mechanism of injury and guide therapeutic trials.Figure: No Caption available.

Symptom Experienced Three Years after Liver Transplantation under Immunosuppression in Adults

Background & AimsImmunosuppression-related symptom experience has not been covered thoroughly in long-term liver transplant recipients. The aim of this study was to assess the symptom experience of immunosuppressive therapy three years after liver transplantation and to correlate it with adherence to medications and sociodemographic or disease-related characteristics.MethodsThis study included 94 liver transplant recipients who had survived for more than 3 years after liver transplantation. Symptom experience was measured by the 59-Item Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) at the outpatient visits. Adherence to immunosuppressive drugs was assessed using the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS).ResultsItching, concentration or memory problems, and fatigue were the three most frequent or most distressing symptoms. Factors significantly associated with a higher level of symptom frequency and distress were 3- to 5-year time cohort (i.e., time post-transplantation), and younger age. At the item level, concentration or memory problems were the most frequent and distressing symptoms in the 3- to 5-year time cohort. Itching was the most frequent and distressing symptom in the 5- to 9-year time cohort. Finally, relationship was found between symptom experience and nonadherence to immunosuppressive drugs.ConclusionsSymptoms related to physical complaints or impairments were more often perceived and more distressing for liver transplant recipients 3 years after transplantation. Furthermore, the 3- to 5-year time cohort and younger age were associated with a higher degree of perceived symptom occurrence and symptom distress. Finally, recipients who perceived higher levels of symptom frequency and symptom distress reported higher levels of nonadherence.

Conversion from twice daily tacrolimus to once daily tacrolimus in long-term stable liver transplant recipients: A single-center experience with 394 patients

After organ transplantation, strategies for simplifying the therapeutic regimen may improve adherence and prevent acute organ rejection and/or late graft loss. The aim of the present study was to evaluate the safety and efficacy of conversion from a tacrolimus (TAC) twice daily (bid) formulation to a once daily (qd) formulation in a large cohort of adult liver transplantation (LT) patients. This retrospective, observational, single-center study included 394 LT patients with at least 6 months' posttransplant follow-up and no rejection episodes in the last 3 months. The conversion from a bid formulation to a qd formulation was based on a 1:1 ratio. The mean age at the time of conversion was 53 years (range = 18-72 years); 66% were men. The main indication for LT was alcoholic cirrhosis (41%). The mean conversion time after LT was 74 months (range = 6-218 months). The mean serum TAC trough level decreased after conversion (6.1 ± 5.6 ng/mL before conversion versus 4.9 ± 2.5 ng/mL after conversion, P < 0.05). After a mean follow-up of 24 months after conversion, 6 patients had converted to cyclosporine, 14 patients had stopped all calcineurin inhibitors, 16 patients had returned to TAC bid, and 358 patients were still on TAC qd. Acute rejection episodes were observed in 7 patients. In conclusion, the results of our experience indicate that the conversion from a TAC bid formulation to a qd formulation is a safe and effective strategy for the management of stable LT patients.

Impact of the Conversion of the Immunosuppressive Regimen from Prograf to Advagraf or to Sirolimus in Long-term Stable Liver Transplant Recipients: Indications, Safety, and Outcome

Background Compliance problems have arisen due to the twice a day administration of calcineurin inhibitors (CNI). We examined the safety, indications, and efficacy in terms of graft and patient survivals after conversion from tacrolimus to Sirolimus or Advagraf. Patients and Methods Between January 2006 and December 2009, 36 orthotopic liver transplantation patients underwent conversion of the immunosuppressive regimen from Prograf to either Sirolimus (group 1; n = 10) or Advagraf (group 2; n = 26). A group of patients taking Prograf was used as a control group (group 3; n = 15). We identified 51 patients of mean age 57 years and male:female percentages of 57%:43% from a prospective database. Renal and liver graft functions, patient survival, as well as laboratory and clinical data over at least 12 months (mean, 38) were the investigated parameters. Results Patients converted to Sirolimus did not show significantly improved renal function at 12 months as evidenced by creatinine levels (1.31 mg/dL +/− 0.47 vs 1.34 mg/dL +/− 0.78) and glomerular filtration rate (GFR, 57+/− 16 vs 56+/− 16 mL/min). However, there were significant antiproliferative effects. Patients with a hepatocellular carcinoma in the pretransplantation phase remained without a recurrence. The side effects including ankle edema, aphthae, and tachyarrhythmia absoluta, required reconversion to the CNI. Patients prescribed Advagraf reported a better life quality because of the single administration and a slight, insignificant improvement in renal function. An acute rejection episode was evidenced under either immunosuppresant. Conclusion Sirolimus is a safe immunosuppressive option in liver transplant recipients suffering from hepatocellular carcinoma. Advagraf showed a lower incidence of side effects than Prograf and probably is not as harmful for renal function, offering better compliance and better life quality.