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Liver Transplant Patients (liver + transplant_patient)

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Selected Abstracts

Long-term Management of the Liver Transplant Patient: Recommendations for the Primary Care Doctor

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009
B. M. McGuire
No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient. [source]

18F-FDG-Uptake of Hepatocellular Carcinoma on PET Predicts Microvascular Tumor Invasion in Liver Transplant Patients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009
A. Kornberg
Vascular invasion of hepatocellular carcinoma (HCC) is a major risk factor for poor outcome after liver transplantation (LT). The aim of this retrospective analysis was to assess the value of preoperative positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) in liver transplant candidates with HCC for predicting microvascular tumor invasion (MVI) and posttransplant tumor recurrence. Forty-two patients underwent LT for HCC after PET evaluation. Sixteen patients had an increased 18F-FDG tumor uptake on preoperative PET scans (PET +), while 26 recipients revealed negative PET findings (PET,) pre-LT. PET, recipients demonstrated a significantly better 3-year recurrence-free survival (93%) than PET + patients (35%, p < 0.001). HCC recurrence rate was 50% in the PET + group, and 3.8% in the PET,population (p < 0.001). PET + status was identified as independent predictor of MVI [hazard ratio: 13.4]. Patients with advanced PET negative tumors and patients with HCC meeting the Milan criteria had a comparable 3-year-recurrence-free survival (80% vs. 94%, p = 0.6). Increased 18F-FDG uptake on PET is predictive for MVI and tumor recurrence after LT for HCC. Its application may identify eligible liver transplant candidates with tumors beyond the Milan criteria. [source]

Dendritic Cell Subset Ratio in Peripheral Blood Correlates with Successful Withdrawal of Immunosuppression in Liver Transplant Patients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2003
George V. Mazariegos
Human dendritic cell (DC) subsets appear to play distinct roles in the induction and regulation of immune responses. While monocytoid DC (DC1) induce T-helper (Th) 1-type responses, plasmacytoid DC (DC2) have been reported to selectively induce Th2 responses. In blood, their precursors (p) can be identified as HLA-DR+ lineage, cells that are further characterized as CD11c+ CD123,/lo (IL-3R,,/lo) (pDC1) or as CD11c, CD123hi (pDC2) by rare event, flow cytometric analysis. We compared the incidences of pDC1 and pDC2 in peripheral blood mononuclear cell populations isolated from normal healthy controls and from 3 groups of clinically stable liver transplant patients. Group A had been successfully withdrawn from immunosuppression, whereas group B were undergoing prospective drug weaning and on minimal anti-rejection therapy. In group C, drug withdrawal had either failed or never been attempted and patients were on maintenance immunosuppression. Assessment of DC subsets and the pDC2 : pDC1 ratio showed good intra-and interassay reproducibility. Compared with patients in group C, those in groups A and B demonstrated a significantly higher relative incidence of pDC2 and a lower incidence of pDC1 , similar to those values observed in normal healthy controls. Moreover, the pDC2 : pDC1 ratio was significantly higher in patients undergoing (successful) weaning and in those off immunosuppression compared with patients on maintenance immunosuppression. [source]

Benefit of Sustained Virological Response to Combination Therapy on Graft Survival of Liver Transplanted Patients with Recurrent Chronic Hepatitis C

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2005
Thierry Bizollon
Recurrent hepatitis C infection is an important cause of progressive fibrosis, cirrhosis and graft loss after liver transplantation. Treatment for post-transplant recurrence results in sustained virological response (SVR) in up to 30% of cases. The aim of this study was to evaluate the impact of SVR on patients and graft survival. Thirty-four patients with an SVR to IFN-ribavirin were included. Forty-six nonresponders to the combination formed the control group. Follow-up data were recorded every 6 months and included HCV RNA, and the occurrence of clinical problems (cirrhosis, decompensation, hepatocellular carcinoma, death). A graft biopsy was performed every year. The mean follow-up duration was 52 months in responders and 57 months in nonresponders. Two patients died in each group of patients. Two patients with SVR developed late virological relapse. Fibrosis decreased in 38% of patients with SVR, remained stable in 44% and worsened in 18%. In contrast, fibrosis increased in the majority of nonresponder patients (74%, p < 0.001). At the end of follow-up, no patient without cirrhosis at inclusion developed cirrhosis of the graft versus 9 among nonresponder patients (p = 0.009). No difference in patient survival was observed in the two groups. In conclusion, this study shows that HCV eradication has a positive impact on graft survival. [source]

The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: A systematic review and meta-analysis,

LIVER TRANSPLANTATION, Issue 7 2004
Nasia Safdar
Selective digestive decontamination (SDD) refers to the use of antimicrobials to reduce the burden of aerobic gram-negative bacteria and/or yeast in the intestinal tract to prevent infections caused by these organisms. Liver transplant patients are highly vulnerable to bacterial infection particularly with gram-negative organisms within the first month after transplantation, and SDD has been proposed as a potential measure to prevent these infections. However, the benefit of this procedure remains controversial. We undertook a systematic review and meta-analysis to determine whether SDD is beneficial in reducing infections overall and those caused by gram-negative bacteria in patients following liver transplantation. All studies that evaluated the efficacy of SDD in liver transplant patients were included. Randomized trials that included liver transplant patients given SDD versus either placebo or no treatment or minimal treatment (e.g., oral nystatin alone), and that provided adequate data to calculate a relative risk ratio, were included in the meta-analysis. Our review shows that most studies found SDD to be effective in reducing gram-negative infection. The nonrandomized and uncontrolled trials also showed benefit with SDD in reducing overall infection; however, the effect on overall infection was limited in the 4 randomized trials, in which the pooled relative risk was 0.88 (95% CI, 0.7-1.1), indicating no statistically significant reduction in infection with the use of SDD. The summary risk ratio for the association between SDD and gram-negative infection was 0.16 (95% CI, 0.07-0.37), indicating an 84% relative risk reduction in the incidence of infection caused by gram-negative bacteria in patients receiving SDD in randomized trials. In conclusion, the available literature supports a beneficial effect of SDD on gram-negative infection following liver transplantation; however, the risk of antimicrobial resistance must be considered. Larger multicenter randomized trials in this patient population to assess the effect of SDD in reducing infection and mortality, while assessing the risk of antimicrobial resistance, are needed. (Liver Transpl 2004;10:817,827.) [source]

Risk of Colorectal Carcinoma in Post-Liver Transplant Patients: A Systematic Review and Meta-analysis

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010
J. Sint Nicolaas
Liver transplant patients (LTx) have an increased risk for developing de novo malignancies, but for colorectal cancer (CRC) this risk is less clear. We aimed to determine whether the CRC risk post-LTx was increased. A systematic search was performed in MEDLINE and Cochrane databases to identify studies published between 1986 and 2008 reporting on the risk of CRC post-LTx. The outcomes were (1) CRC incidence rate (IR per 100 000 person-years (PY)) compared to a weighted age-matched control population using SEER and (2) relative risk (RR) for CRC compared to the general population. If no RR data were available, the RR was estimated using SEER. Twenty-nine studies were included. The overall post-LTx IR was 119 (95% CI 88,161) per 100 000 PY. The overall RR was 2.6 (95% CI 1.7,4.1). The non-primary sclerosing cholangitis (PSC) IR was 129 per 100 000 PY (95% CI 81,207). Compared to SEER (71 per 100 000 PY), the non-PSC RR was 1.8 (95% CI 1.1,2.9). In conclusion, the overall transplants and the subgroup non-PSC transplants have an increased CRC risk compared to the general population. However, in contrast to PSC, non-PSC transplants do not need an intensified screening strategy compared to the general population until a prospective study further defines recommendations. [source]

Concomitant and fatal HHV-8+ multicentric Castleman's disease and Kaposi's sarcoma in the same lymph node of an HIV, liver transplant patient

HISTOPATHOLOGY, Issue 7 2007
S Gaitonde
First page of article [source]

Lymphocutaneous nocardiosis and cutaneous pheohyphomycosis in a liver transplant recipient

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2008
Isabel Hidalgo Parra
Background, Infections are the leading cause of morbidity and mortality in transplanted patients. The increasing number of immunocompromised patients has not only augmented infections by specific pathogens, but also by opportunistic microbial agents. Methods, A mixed cutaneous infection caused by Nocardia brasiliensis and Exophiala jeanselmei is reported in a liver transplant patient. Results, The cutaneous lesions were painful nodules which drained purulent material. They were located on the right lower limb, with lymphadenopathies in the groin. Conclusions, The patient was treated with itraconazole (600 mg/day) plus trimethoprim (1600 mg/day),sulfamethoxazole (320 mg/day) for 8 weeks, with complete remission of the lesions. [source]

Kinetics of host immune responses and cytomegalovirus resistance in a liver transplant patient

LIVER TRANSPLANTATION, Issue 10 2009
Kirsten Schaffer
Among solid organ transplant (SOT) recipients, donor-seropositive/recipient-seronegative (D+/R,) cytomegalovirus (CMV) status is associated with the highest risk of ganciclovir-resistant CMV disease, which has been reported for patients receiving oral ganciclovir but not valganciclovir prophylaxis. We report a case of CMV breakthrough infection in a D+/R, liver transplant patient while he was receiving oral valganciclovir. Forty samples collected over 6 months were analyzed for the CMV viral load, lymphocyte counts, cytokine levels, and lymphocyte differentiation status. Genotypic resistance testing of the viral UL97 gene was performed when the patient failed to respond. CMV viremia occurred on day 50 post-transplant, and 5 samples taken between days 50 and 85 showed the wild-type UL97 genotype. The appearance of deletion 594-595 was observed from day 114 post-transplant. Viral loads declined when foscarnet was commenced and remained below 10,000 copies/mL when the lymphocyte count was greater than 1000/,L (P = 0.02). T cell responses revealed significant expansion of CD8+ terminal effector memory cells. CD4+ cells were largely populations of naïve and central memory cells. Circulating interleukin 10 (IL-10) levels correlated with the viral load (P < 0.0001). Seroconversion occurred on day 230. The CMV viral load in combination with lymphocyte counts and IL-10 may be a predictive marker for the risk of development of resistant CMV disease in D+/R, SOT patients. Liver Transpl 15:1199,1203, 2009. © 2009 AASLD. [source]

Cure of Acanthamoeba cerebral abscess in a liver transplant patient

LIVER TRANSPLANTATION, Issue 3 2008
Konrad Tang-Tat Fung
Acanthamoeba-related cerebral abscess and encephalitis are rare but usually fatal, being caused by free-living amoebic infections usually occurring in immunocompromised patients. In patients receiving transplants, a literature review showed that the infection is universally fatal. The diagnosis is often missed despite appropriate investigations including lumbar puncture, computerized tomography, and brain biopsy. We present the first reported liver transplant patient with Acanthamoeba cerebral abscess. The diagnosis was made in brain tissue removed at decompressive frontal lobectomy. He was successfully treated with a 3-month course of co-trimoxazole and rifampicin. There was no recurrence of the disease after 11 years of follow-up. Liver Transpl 14:308,312, 2008. © 2008 AASLD. [source]

Long-term management of the liver transplant patient

LIVER TRANSPLANTATION, Issue 11B 2001
Michael F. Sorrell MD
[source]

Long-term Management of the Liver Transplant Patient: Recommendations for the Primary Care Doctor

Nephrogenic Systemic Fibrosis Among Liver Transplant Recipients: A Single Institution Experience and Topic Update

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2006
M. Maloo
Nephrogenic systemic fibrosis (NSF) is a recently characterized systemic fibrosing disorder developing in the setting of renal insufficiency. NSF's rapidly progressive nature resulting in disability within weeks of onset makes early diagnosis important. Two reports of NSF after liver transplantation are known of. We present three cases of NSF developing within a few months after liver transplantation and review the current literature. Loss of regulatory control of the circulating fibrocyte, its aberrant recruitment, in a milieu of renal failure and a recent vascular procedure appear important in its development. Known current therapies lack consistent efficacy. Only an improvement in renal function has the greatest likelihood of NSF's resolution. Delayed recognition may pose a significant barrier to functional recovery in the ubiquitously deconditioned liver transplant patient. Early recognition and implementation of aggressive physical therapy appear to have the greatest impact on halting its progression. [source]

Relationships of tacrolimus pharmacokinetic measures and adverse outcomes in stable adult liver transplant recipients

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2006
C. Dansirikul PhD
Summary Background and objectives:, Alternative measures to trough concentrations [non-trough concentrations and limited area under the concentration,time curve (AUC)] have been shown to better predict tacrolimus AUC. The aim of this study was to determine if these are also better predictors of adverse outcomes in long term liver transplant recipients. Methods:, The associations between tacrolimus trough concentrations (C0), non-trough concentrations (C1, C2, C4, C6/8), and AUC0,12 and the occurrence of hypertension, hyperkalaemia, hyperglycaemia and nephrotoxicity were assessed in 34 clinically stable liver transplant patients. Results and discussion:, The most common adverse outcome was hypertension, prevalence of 36%. Hyperkalaemia and hyperglycaemia had a prevalence of 21% and 13%, respectively. A sequential population pharmacokinetic/pharmacodynamic approach was implemented. No significant association between predicted C0, C1, C2, C4, C6/8 or AUC0,12 and adverse effects could be found. Tacrolimus concentrations and AUC measures were in the same range in patients with and without adverse effects. Conclusions:, Measures reported to provide benefit, preventing graft rejection and minimizing acute adverse effects in the early post-transplant period, were not able to predict adverse effects in stable adult liver recipients whose trough concentrations were maintained in the notional target range. [source]

Elevated levels of soluble fibrin or D-dimer indicate high risk of thrombosis

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2006
H. WADA
Summary.,Background:,Fibrin-related markers such as soluble fibrin (SF) and D-dimer are considered useful for the diagnosis of thrombosis. However, the evidence for diagnosis of thrombosis by fibrin-related markers is not well-established. Objective:,To evaluate the cutoff values of D-dimer and SF in the diagnosis of thrombosis. Patients and Methods:,Plasma concentrations of SF and D-dimer were measured in 784 inpatients suspected of having thrombosis between 1 August 2003 and 31 December 2004, and then correlated with thrombosis. Results and Conclusions:,Plasma concentrations of D-dimer and SF were significantly higher in patients with disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT) and cerebral thrombosis, compared with those in patients without thrombosis. When cutoff values of > 3.0 ,g mL,1 for D-dimer and > 6.0 ,g mL,1 for SF were used for the diagnosis, more than 50% of patients (with the exception of liver transplant patients and postoperative patients) had thrombosis. Receiver operating characteristic analysis showed that SF was more useful than D-dimer for the diagnosis of thrombosis (i.e. DVT and DIC). The cutoff value of D-dimer (7.87 ,g mL,1) was the same for DVT and DIC, while that of SF was slightly lower for DVT (7.05 ,g mL,1) than for DIC (8.60 ,g mL,1). Our findings suggest that high levels of plasma fibrin-related markers reflect high risk for thrombosis. [source]

Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients

LIVER TRANSPLANTATION, Issue 1 2010
Sven Pischke
Hepatitis E virus (HEV) infection induces self-limiting liver disease in immunocompetent individuals. Cases of chronic hepatitis E have recently been identified in organ transplant recipients. We questioned if chronic hepatitis E plays a role in graft hepatitis after liver transplantation in a low endemic area. Two hundred twenty-six liver transplant recipients, 129 nontransplanted patients with chronic liver disease, and 108 healthy controls were tested for HEV antibodies. HEV RNA was investigated in all sera from transplanted patients. HEV antibodies were detected in 1 healthy control (1%), 4 patients with chronic liver disease (3%), and 10 liver transplant recipients (4%). Three liver transplant patients also tested positive for HEV RNA. Two of them developed persistent viremia with HEV genotype 3. The patients were anti-HEV immunoglobulin G,negative and HEV RNA,negative before transplantation and had an episode of acute hepatitis 5 or 7 months after transplantation, which led to advanced liver fibrosis after 22 months in 1 patient. Seroconversion to anti-HEV occurred not before 4 months after the first detection of HEV RNA. The possibility of reverse zoonotic transmission was experimentally confirmed by the infection of 5 pigs with a patient's serum. The pigs showed histological inflammation in the liver, and HEV RNA was detectable in different organs, including muscle. In conclusion, the prevalence of HEV infection in Central European liver transplant recipients is low; however, chronic hepatitis E may occur and needs to be considered in the differential diagnosis of graft hepatitis. The diagnosis of HEV infection should be based on HEV RNA determination in immunosuppressed patients. We suggest that immunocompromised individuals should avoid eating uncooked meat and contact with possibly HEV-infected animals. Liver Transpl 16:74,82, 2010. © 2009 AASLD. [source]

Enfuvirtide: A safe and effective antiretroviral agent for human immunodeficiency virus,infected patients shortly after liver transplantation

LIVER TRANSPLANTATION, Issue 10 2009
Elina Teicher
The aim of this study was to evaluate the impact of an enfuvirtide-based antiretroviral (ARV) regimen on the management of immunosuppression and follow-up in hepatitis C virus (HCV)/hepatitis B virus (HBV)/human immunodeficiency virus (HIV),coinfected liver transplant patients in comparison with a lopinavir/ritonavir-based ARV regimen. Tacrolimus and cyclosporine trough concentrations were determined at a steady state during 3 periods: after liver transplantation without ARV treatment (period 1), at the time of ARV reintroduction (period 2), and 2 to 3 months after liver transplantation (period 3). The findings for 22 HIV-coinfected patients were compared (18 with HCV and 4 with HBV); 11 patients were treated with enfuvirtide and were matched with 11 lopinavir/ritonavir,exposed patients. During period 1, tacrolimus and cyclosporine A doses were 8 and 600 mg/day, respectively, and the trough concentrations were within the therapeutic range in both groups. In period 2, the addition of lopinavir/ritonavir to the immunosuppressant regimen enabled a reduction in the dose of immunosuppressants required to maintain trough concentrations within the therapeutic range (to 0.3 mg/day for tacrolimus and 75 mg/day for cyclosporine). Immunosuppressant doses were not modified by the reintroduction of enfuvirtide, there being no change in the mean trough concentrations over the 3 periods. CD4 cell counts remained at about 200 cells/mm. The HIV RNA viral load remained undetectable. Both groups displayed signs of mild cytolysis and cholestasis due to the recurrence of HCV, whereas no renal insufficiency was observed. Enfuvirtide is an attractive alternative to standard ARV therapy, facilitating the management of drug-drug interactions shortly after liver transplantation. Moreover, the lack of liver toxicity renders this drug valuable in the event of a severe HCV recurrence. Liver Transpl 15:1330,1335, 2009. © 2009 AASLD. [source]

Worse recent efficacy of antiviral therapy in liver transplant recipients with recurrent hepatitis C: Impact of donor age and baseline cirrhosis,

LIVER TRANSPLANTATION, Issue 7 2009
Marina Berenguer
We hypothesized that antiviral efficacy [sustained virologic response (SVR)] has improved in recent years in the transplant setting. Our aim was to assess whether the efficacy of pegylated interferon (PegIFN),ribavirin (Rbv) has improved over time. One hundred seven liver transplant patients [74% men, 55.5 years old (range: 37.5,69.5), 86% genotype 1a or 1b] were treated with PegIFN-Rbv for 355 (16,623) days at 20.1 (1.7,132.6) months after transplantation. Tacrolimus was used in 61%. Sixty-seven percent had baseline F3,F4 (cirrhosis: 20.5%). Donor age was 49 (12,78) years. SVR was achieved in 39 (36.5%) patients, with worse results achieved in recent years (2001,2003: n = 27, 46.5%; 2004: n = 23, 43.5%; 2005: n = 21, 35%; 2006 to January 2007: n = 36, 24%; P = 0.043). Variables associated with SVR in the univariate analysis included donor age, baseline viremia and cirrhosis, bilirubin levels, rapid virologic response and early virologic response (EVR), premature discontinuation of PegIFN or Rbv, and accumulated Rbv dose. In the multivariate analysis, the variables in the model were EVR [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.016,0.414, P = 0.002] and donor age (OR: 1.039, 95% CI: 1.008,1.071, P = 0.01). Variables that had changed over time included donor age, baseline viremia, disease severity (cirrhosis, baseline bilirubin, and leukocyte and platelet counts), interval between transplantation and therapy, and use of growth factors. In the multivariate analysis, variables independently changing were donor age (OR: 1.041, 95% CI: 1.013,1.071, P = 0.004), duration from transplantation to antiviral therapy (OR: 1.001, 95% CI: 1.000,1.001, P = 0.013), and baseline leukocyte count (OR: 1.000, 95% CI: 1.000,1.000, P = 0.034). In conclusion, the efficacy of antiviral therapy with PegIFN-Rbv has worsened over time, at least in our center. The increase in donor age and greater proportion of patients treated at advanced stages of disease are potential causes. Liver Transpl 15:738,746, 2009. © 2009 AASLD. [source]

Graft rejection occurring in post,liver transplant patients receiving cytotoxic chemotherapy: A case series

LIVER TRANSPLANTATION, Issue 6 2009
Hui-Hui Tan
Liver transplant recipients are known to be at increased risk for the development of de novo neoplasms or the recurrence of preexisting malignancies, and this is possibly related to the use of immunosuppressive medication. Little is known about the effects of cytotoxic chemotherapy on graft function after transplantation. A retrospective chart and pathology database review was undertaken to identify post,liver transplant patients developing rejection during chemotherapy. All liver biopsies were reviewed by a hepatopathologist. Three patients were identified. All patients were diagnosed with cancer within 7 years of liver transplantation; two-thirds died soon after the diagnosis of malignancy. Rejection occurred soon after chemotherapy was started. All patients were receiving prednisone and tacrolimus (trough levels: 2.1-4.8 ng/mL). One patient developed plasma cell hepatitis (de novo autoimmune hepatitis). There was no histologic evidence of hepatotoxicity due to the chemotherapeutic agents. Cytotoxic chemotherapy should be used in liver transplant recipients with caution, and immunosuppressant doses should be maintained at therapeutic levels, as patients may be at risk for allograft rejection. Treatment of rejection or plasma cell hepatitis in this setting should be undertaken in a timely and aggressive fashion to prevent chronic ductopenic rejection. Liver Transpl 15:634,639, 2009. © 2009 AASLD. [source]

Health-related quality of life and employment status of liver transplant patients

LIVER TRANSPLANTATION, Issue 1 2009
Fredrik Åberg
Health-related quality of life (HRQoL) is one preferable outcome measure of medical interventions such as liver transplantation (LT). The aim of this study was to compare HRQoL of LT patients with that of the general population and to assess the employment status of LT patients. HRQoL was measured with the 15D instrument, a validated, non,disease-specific, 15-dimensional, self-administered HRQoL instrument. The questionnaire was sent to all adult LT patients in Finland (401 patients) alive in June 2007. The response rate was 89% (353 patients). The results were compared to those of 6050 age-standardized and gender-standardized controls from the general population. LT patients (mean age, 55 years; range, 20-82) had slightly worse HRQoL scores than the general population (mean 15D score, 0.889 versus 0.907; P < 0.002). Survival time and retransplantation did not affect HRQoL significantly in age-adjusted and gender-adjusted analyses. HRQoL decreased with increasing age (P < 0.0001). Patients transplanted for acute liver failure (ALF) or chronic liver disease (CLD) had significantly worse HRQoL than the general population (P = 0.014 and P = 0.040). Forty-four percent of working-age patients were employed at the time of the study. Persons that were employed had significantly better HRQoL than those unemployed (15D scores, 0.934 versus 0.859; P < 0.0001). Eighty-seven percent of patients experienced improved working capacity after LT. Early retirement was the most common cause of unemployment (56% of unemployed patients), and those patients presented with worse HRQoL than patients unemployed for other reasons. In conclusion, HRQoL of LT patients is very close to that of the general population. Older age, CLD, and ALF impair HRQoL. Employment is an indicator of HRQoL. Liver Transpl 15:64,72, 2009. © 2008 AASLD. [source]

Reducing coronary artery disease events in liver transplant patients: Moving toward identifying the vulnerable patient,

LIVER TRANSPLANTATION, Issue 12 2008
Christopher P. Appleton
[source]

Liver transplantation and subsequent risk of cancer: Findings from a Canadian cohort study,

LIVER TRANSPLANTATION, Issue 11 2008
Ying Jiang
Characterization of the long-term cancer risks among liver transplant patients has been hampered by the paucity of sufficiently large cohorts. The increase over time in the number of liver transplants coupled with improved survival underscores the need to better understand associated long-term health effects. This is a cohort study whose subjects were assembled with data from the population-based Canadian Organ Replacement Registry. Analyses are based on 2034 patients who received a liver transplant between June 1983 and October 1998. Incident cases of cancer were identified through record linkage to the Canadian Cancer Registry. We compared site-specific cancer incidence rates in the cohort and the general Canadian population by using the standardized incidence ratio (SIR). Stratified analyses were performed to examine variations in risk according to age at transplantation, sex, time since transplantation, and year of transplantation. Liver transplant recipients had cancer incidence rates that were 2.5 times higher than those of the general population [95% confidence interval (CI) = 2.1, 3.0]. The highest SIR was observed for non-Hodgkin's lymphoma (SIR = 20.8, 95% CI = 14.9, 28.3), whereas a statistically significant excess was observed for colorectal cancer (SIR = 2.6, 95% CI = 1.4, 4.4). Risks were more pronounced during the first year of follow-up and among younger transplant patients. In conclusion, our findings indicate that liver transplant patients face increased risks of developing cancer with respect to the general population. Increased surveillance in this patient population, particularly in the first year following transplantation, and screening for colorectal cancer with modalities for which benefits are already well recognized should be pursued. Liver Transpl 14:1588,1597, 2008. © 2008 AASLD. [source]

Recipient and donor factors influence the incidence of graft-vs.-host disease in liver transplant patients

LIVER TRANSPLANTATION, Issue 4 2007
Edie Y. Chan
Acute cellular graft-vs.-host disease (GVHD) following liver transplantation has an incidence of 1 to 2% and a mortality rate of 85%. Our aim was to identify a patient population at high risk for developing GVHD using a large clinical database to study both recipient and donor factors. We compared our liver transplant patients who developed GVHD to those that did not for recipient and donor factors and combinations of factors. For 2003,2004 we had 205 first-time liver transplant patients surviving >30 days. From this group, 4 (1.9%) developed GVHD. Compared to the control group, there were no significant differences in recipient age, recipient gender, donor age, donor gender, total ischemia time, donor-recipient human leukocyte antigen (HLA) mismatch, or donor-recipient age difference. Percentages of liver disease etiologies among the patients who developed GVHD were as follows: 16% (1/6) autoimmune hepatitis (AIH) (P = 0.003), 5.6% (3/54) alcoholic liver disease (ALD) (P = 0.057), and 7.1% (3/42) hepatocellular carcinoma (HCC) (P = 0.026). The incidence of GVHD in patients with glucose intolerance (either Type I or Type II diabetes mellitus [DM]) was significant (P = 0.022). Focusing on patients only with high-risk factors for GVHD during the years 2003,2005, we had 19 such patients. Four of these high-risk patients developed GVHD. Three of these 4 patients had received a donor liver with steatosis of degree ,mild compared to only 2 of the 15 high-risk patients who did not develop GVHD (P = 0.037). In conclusion, we have identified liver transplant patients with AIH or the combination of ALD, HCC, and glucose intolerance who receive a steatotic donor liver as being at high risk for developing GVHD. Liver Transpl 13:516,522, 2007. © 2007 AASLD. [source]

12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus,,

LIVER TRANSPLANTATION, Issue 10 2006
Gary Levy
The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C,positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 ± 50 days) than with tacrolimus (70 ± 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 ,mol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline. Liver Transpl 12:1464,1472, 2006. © 2006 AASLD. [source]

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients presenting gastrointestinal disorders: A pilot study

LIVER TRANSPLANTATION, Issue 9 2006
Jérôme Dumortier
Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in liver transplant patients presenting GI side-effects Since January 2003, stable liver transplant patients receiving MMF and presenting GI disorders, without evidence of other origin than MMF were enrolled. Conversion was performed without a washout period at an equimolar daily dosage. Thirty-six patients were included after a median delay of 45 months after liver transplantation (LT) (16 women and 20 men, median age of 47 years). Diarrhoea was the main clinical symptom (n = 28, 77.7%). At the time of inclusion, patients were treated with MMF since 18 months (range 3-28) and GI disorders were known for 9 months (range 3-12). After a median follow-up of 12 months after conversion, GI disorders were resolved in 20 patients (55%), improved in 6 patients (17%) and not modified or worsened in 10 patients (28%). Our results strongly suggest that conversion from MMF to EC-MPS in liver transplant patients can improve gastrointestinal disorders in a majority of the patients, and therefore might be considered as the best therapeutic option. Liver Transpl 12:1342-1346, 2006. © 2006 AASLD. [source]

Cyclosporine exposure and calcineurin phosphatase activity in living-donor liver transplant patients: Twice daily vs. once daily dosing

LIVER TRANSPLANTATION, Issue 2 2006
Masahide Fukudo
We have compared the pharmacokinetics and pharmacodynamics of cyclosporine between once- and twice-daily dosing regimens in de novo patients of living-donor liver transplantation (LDLT). A total of 14 patients were enrolled in this study, who had received cyclosporine microemulsion (Neoral) twice a day (BID, n = 5) or once daily in the morning (QD, n = 9) after transplantation. On postoperative day (POD) 6, the QD regimen significantly increased cyclosporine exposure; the blood concentration at 2 hours postdose (C2) and area under the concentration-time curve (AUC) for 4 hours (AUC0,4), compared with the BID regimen. Moreover, the area under the calcineurin (CaN) activity in peripheral blood mononuclear cells time-curve (AUA) for 12 hours (AUA0,12) and 24 hours (AUA0,24) were decreased by approximately 42 and 25% with the QD regimen relative to the BID regimen, respectively. The C2 level was significantly correlated with the AUC0,4 (r2 = 0.95), which was negatively related to the AUA0,12 with a large interindividual variability (r2 = 0.59). However, a significant correlation was found between the AUA0,12 or AUA0,24 and CaN activity at trough time points. According to a maximum inhibitory effect attributable to the drug (Emax) model, the mean estimates of Emax and the Cb value that gives a half-maximal effect (EC50) for CaN inhibition were not significantly different between the 2 groups, respectively. These findings suggest that a once daily morning administration of cyclosporine may improve oral absorption and help to provide an effective CaN inhibition early after LDLT. Furthermore, CaN activity at trough time points would be a single surrogate predictor for the overall CaN activity throughout dosing intervals following cyclosporine administration. Liver Transpl 12:292,300, 2006. © 2006 AASLD. [source]

How common is delayed cyclosporine absorption following liver transplantation?

LIVER TRANSPLANTATION, Issue 2 2005
Silvina E. Yantorno
The mean time to peak absorption of cyclosporine (CsA) in liver transplant patients is approximately 2 hours, but in some patients the peak occurs later. The goal of this study was, therefore, to investigate the incidence of delayed absorption in 27 de novo liver transplant recipients receiving CsA ,10 mg/kg/day (C2 monitoring) and in 15 maintenance patients. Patients were categorized as ,normal' absorbers (C2 exceeding C4 and C6) or ,delayed' absorbers (C4 or C6 exceeding C2), and as ,good' (>800 ng/mL at C0, C2, C4, or C6) or ,poor' absorbers (C0, C2, C4 and C6 <800 ng/mL) on the day of study. Among de novo patients, 15 (56%) had ,normal' CsA absorption and 12 (44%) ,delayed' absorption. Good CsA absorption occurred in 16 patients (59%) and poor absorption in 11 (41%). The proportion of poor absorbers was similar in patients with normal (6 / 15, 40%) or delayed (5 / 12, 42%) absorption. Among the 12 delayed absorbers, 11 had peak CsA concentration at C4. Mean C0 level was significantly higher in delayed absorbers (282 ± 96 ng/mL) than in normal absorbers (185 ± 88ng/mL; P = .01). Delayed absorbers reverted to normal absorption (C2 > C4) after a median of 6 days from the day of study, and no cases of delayed absorption were found among maintenance patients. In conclusion, almost 50% of the patients had delayed CsA absorption early posttransplant; around half of these exhibited normal CsA exposure. Measurement of C4 in addition to C2 differentiates effectively between delayed and poor absorbers of CsA such that over- or underimmunosuppression can be avoided. (Liver Transpl 2005;11:167,173.) [source]

Factors that identify survival after liver retransplantation for allograft failure caused by recurrent hepatitis C infection

LIVER TRANSPLANTATION, Issue 12 2004
Guy W. Neff
Hepatitis C virus (HCV) is becoming the most common indication for liver retransplantation (ReLTx). This study was a retrospective review of the medical records of liver transplant patients at our institution to determine factors that would identify the best candidates for ReLTx resulting from allograft failure because of HCV recurrence. The patients were divided into 2 groups on the basis of indication for initial liver transplant. Group 1 included ReLTx patients whose initial indication for LTx was HCV. Group 2 included patients who received ReLTx who did not have a history of HCV. We defined chronic allograft dysfunction (AD) as patients with persistent jaundice (> 30 days) beginning 6 months after primary liver transplant in the absence of other reasons. HCV was the primary indication for initial orthotopic liver transplantation (OLT) in 491/1114 patients (44%) from July 1996 to February 2004. The number of patients with AD undergoing ReLTx in Groups 1 and 2 was 22 and 12, respectively. The overall patient and allograft survival at 1 year was 50% and 75% in Groups 1 and 2, respectively (P = .04). The rates of primary nonfunction and technical problems after ReLTx were not different between the groups. However, the incidence of recurrent AD was higher in Group 1 at 32% versus 17% in Group 2 (P = .04). Important factors that predicted a successful ReLTx included physical condition at the time of ReLTx (P = .002) and Child-Turcotte-Pugh score (P = .008). In conclusion, HCV is associated with an increased incidence of chronic graft destruction with a negative effect on long-term results after ReLTx. The optimum candidate for ReLTx is a patient who can maintain normal physical activity. As the allograft shortage continues, the optimal use of cadaveric livers continues to be of primary importance. The use of deceased donor livers in patients with allograft failure caused by HCV remains a highly controversial issue. (Liver Transpl 2004;10:1497,1503.) [source]

The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: A systematic review and meta-analysis,

C2 monitoring of cyclosporine in de novo liver transplant recipients: The clinician's perspective

LIVER TRANSPLANTATION, Issue 5 2004
Federico Villamil
Adjusting cyclosporine (CsA) dose based on blood concentration at 2 hours after dose (C2) has been shown in prospective clinical trials to reduce the risk of rejection compared with conventional trough monitoring. In addition, it provides equivalent efficacy to tacrolimus in liver transplant patients, with a favorable safety profile. Target C2 should be defined on an individual basis depending on adjunctive therapy and the level of exposure required. It appears less critical to achieve target C2 in the first few days after liver transplantation than was previously believed. Achieving target C2 exposure in the initial period after transplant requires that changes in the proportion of cyclosporine absorbed from the gut be taken into account to avoid risk of overexposure. In addition, if a starting dose of 10,15 mg/day is used, it is advisable to delay increasing the dose until a trend in C2 level indicates this to be necessary. Immediate dose reduction is required if C2 exceeds target range. In patients with low C2 values, cyclosporine concentration at a later time point should be measured to establish whether the patient is a poor absorber or a delayed absorber of C2, and dose adjustments should be undertaken accordingly. In conclusion, this more flexible approach to C2 monitoring allows the dose of cyclosporine to be individualized effectively for each patient, which results in significant efficacy benefits while minimizing the risk of toxicity. (Liver Transpl 2004;10:577,583.) [source]