Validation of cardiovascular risk scores in a liver transplant population.

Increased prevalence of cardiovascular risk factors has been acknowledged in liver transplant recipients, and an increased incidence of cardiovascular events has been suspected. Individual risk determination, however, has not yet been established. Outpatient charts of 438 primary liver transplants have been reviewed, and suspected cardiovascular risk factors were correlated with cardiovascular events observed during a follow-up period of 10 yr. Receiver operation characteristics curve (ROC) analysis was performed to validate established cardiovascular risk scores. For calibration, the Hosmer-Lemeshow test was performed. A total of 303 of 438 patients were available for risk factor analysis at 6 months and demonstrated complete follow-up data (175 male, 128 female). A total of 40 of those 303 patients experienced fatal or nonfatal cardiovascular events (13.2%). In univariate analysis, age (P < 0.001), gender (P = 0.002), body mass index (P = 0.018), cholesterol (P = 0.044), creatinine (P = 0.006), diabetes mellitus (P = 0.017), glucose (0.006), and systolic blood pressure (P = 0.043), but not cyclosporine A (P = 0.743), tacrolimus (P = 0.870), or steroid medication (P = 0.991), were significantly associated with cardiovascular events. Multivariate analysis, however, identified only age, gender, and cholesterol as independent predictors. In ROC analysis, corresponding areas under the curve for Systematic Coronary Risk Evaluation Project (SCORE), Prospective Cardiovascular Münster Study (PROCAM), and Framingham risk scores (FRSs) were calculated with 0.800, 0.778, and 0.707, respectively. Calibration demonstrated an improved goodness of fit for PROCAM compared to SCORE risk calculations. In conclusion, SCORE and PROCAM proved to be valuable in discriminating our liver transplant recipients for their individual risk of cardiovascular events. Furthermore, calibrated PROCAM risk estimates are required to calculate the number of patients needed to treat in the setup of prospective intervention trials.     

Nonhepatitis B-associated liver disease in a renal transplant population

The spectrum of liver disease in a population of 293 patients receiving 353 renal transplants (1971-1984) was reviewed. This study looked retrospectively at the histological features of liver disease in this population, and prospectively at the clinical and biochemical features of liver disease associated with renal transplantation. In all patients, infection with hepatitis B was excluded. Six deaths, primarily attributable to hepatic failure have occurred: one, acute herpes simplex infection; one, subacute massive hepatic necrosis of uncertain etiology; two, pretransplant liver disease; and two, posttransplantation cirrhosis of uncertain etiology. Review of the hepatic histology of 26 patients with known liver disease following transplantation revealed a wide range of pathologies with few specific correlations with their clinical status or biochemical tests of liver function. The prevalence of hepatic dysfunction following transplantation in our patient population was assessed by prospective biochemical screening of 111 transplant recipients over a 6-month interval. During this time period, 27 patients (24%) displayed biochemical evidence of hepatic dysfunction. Liver disease was known to have predated transplantation in only three of 27. Episodes of abnormal liver function occasionally occurred during an identifiable acute illness (six of 27), although the majority (21 of 27) had chronic hepatic dysfunction. Transplant recipients with abnormal liver function could not be differentiated from a cohort with normal liver function on the basis of age, sex, duration of graft function, or alcohol/drug intake. The possible etiologies of nonhepatitis B liver dysfunction following renal transplantation are discussed, and the high prevalence of biochemical evidence of hepatic dysfunction in this population free of hepatitis B infection is emphasized.     

Dietary supplements and herbal preparations in renal and liver transplant recipients

Background

Dietary supplements (DS) and herbal preparations (HP) are advertised to be safe and have therapeutic potential. They are sold over the counter. Therefore, a considerable increase in the frequency of their use has been observed; for example in the United States one in four persons taking medicines uses DS. The use of DS and HP in renal and liver transplant recipients remains unknown.

Objectives

The aim of our study was to determine the proportion of patients who used DS or HP, as well as to assess their awareness of the benefits and risks related to ingestion of these products.

Methods

We enrolled 100 renal, liver, or combined renal and heart transplant patients into the study. They underwent a survey consisting of 14 multiple-choice questions, concerning demographic features, transplant-related data, and information about the use of DS and HP, including the frequency of use, the reasons for the purchase, the knowledge of risks and benefits, as well as the sources of information about these products.

Results

Among the 58 (58%) patients who admitted their use of DS and/or HP, 20 (34.5%) ingested more than one preparation. Among liver patients, 51%, and among renal, 44%, of patients took these products for a variety of indications. Vitamins, minerals, diuretics, gastrointestinal tract-regulating, and sedative herbs were chosen most frequently. While 27% of respondents alleged to have obtained the information on DS and HP from a physician, 14% were from a pharmacist, 9% from a friend, acquaintance or neighbor, 8% from an attached leaflet, 4% from an advertisement, and 4% from the internet.

Conclusions

A high proportion of patients use DS and HP. Most preparations were taken without medical consultation. Awareness of their toxicity or drug interactions was low. Therefore, a tailored education program should be proposed for this group of patients.     

Disseminated histoplasmosis in a liver transplant recipient.

A 61-yr-old liver transplant recipient presented with abdominal cramping and nonbloody diarrhea resulting in orthostasis. Multiple ulcerations throughout the colon were seen during endoscopy, and biopsies from the ulcer edges revealed histoplasmosis. Treatment with a course of itraconazole improved the diarrhea. The patient later presented with pericarditis and symptomatic pleural effusions, the latter of which was confirmed to be a result of disseminated histoplasmosis. Treatment with amphotericin B led to resolution. Histoplasmosis should be considered in liver transplant patients with diarrhea and large ulcers in the colon. The presence of disseminated histoplasmosis should be ruled out once colonic histoplasmosis has been diagnosed.     

Endoscopic retrograde cholangiography in post-orthotopic liver transplant population with Roux-en-Y biliary reconstruction.

Endoscopic retrograde cholangiography (ERC) is a well-established modality for diagnostic and therapeutic maneuvers in pancreaticobiliary disorders. However, it is technically more challenging in patients with postsurgical anatomy like Roux-en-Y anastomoses. Its effectiveness in post-orthotopic liver transplantation (OLT) patients with Roux-en-Y biliary reconstruction has not been reported. We sought to assess the efficacy and safety of ERC in this patient population. A total of 132 OLTs with Roux-en-Y biliary reconstruction were performed at our institution from June 1998 to August 2005. Data from consenting patients who underwent ERC were reviewed once they were identified through computerized medical index system. Of 132 OLT patients with Roux-en-Y biliary reconstruction, 31 patients (9 female and 22 male subjects ranging in age from 11 months to 70 years) underwent ERC. The indication for liver transplant was end-stage liver disease or occurrence of cholangiocarcinoma from primary sclerosing cholangitis in 28 patients and a case each of chronic hepatitis C, alcoholic liver disease, and metastatic islet cell carcinoma. A variable-stiffness pediatric colonoscope was used in most cases. ERC indications were both diagnostic and therapeutic and included the following: evaluation of increased liver biochemistries and fever in 12 patients, dilation of anastomotic biliary strictures in 10 patients, removal of fractured biliary tube or retained biliary stent in 6 patients, and in 1 patient each, biliary stone removal, management of bile leak, and jejunal tube extension placement for nutritional purpose. ERC was successful in 22 patients (71%). There were no postprocedural complications. Although ERC is technically more difficult and time-consuming in OLT patients with Roux-en-Y anastomoses, these data suggest that ERC is an effective and safe diagnostic and therapeutic modality with few or no complications when performed by experienced endoscopists. ERC was successful in most patients and allowed therapeutic interventions that obviated the need for percutaneous radiological intervention or surgery.     

Orthopaedic referrals from a cardiothoracic transplant population.

In this study we audited the orthopaedic referrals from the cardiothoracic transplant population at Wythenshawe Hospital, South Manchester. A total of 33 referrals in 29 patients were made during the period of study. The referrals represented 10.3% (33/321) of the transplant population. However, the rate of referral per postoperative year was 37.9/1000, which was of a similar order to that of the general population. The diagnosis at referral was activity related in 24 (72.7%) referrals, with one-half of these being related to some form of sporting activity. Complications of immunosuppression may have contributed in up to 15 (45.4%) of referrals. We believe that musculoskeletal problems after cardiothoracic transplantation do not place an excessive burden on our orthopaedic department and that the pattern of referrals indicates that the transplant programme is a success.     

Dermatologic lesions in a transplant population

Many authors have reported an increase in the incidence of skin neoplasia in renal transplant patients. Two hundred and twenty-three patients, who received a renal transplants between 1965 and 1984, were examined for the presence of skin lesions. There was a high incidence of simple warts (24%) and hyperkeratoses (21%). Frank malignancy had developed in 9 patients; this is more than 4 times the expected incidence for the population of Northern Ireland.     

Graft involvement by Legionella in a liver transplant recipient.

Legionella pneumophila, serogroup 1, was identified by direct immunofluorescence in the lung and liver graft from a 2 1/2-month-old infant who underwent orthotopic liver transplantation because of fulminant hepatic failure secondary to neonatal hepatitis. The patient died of respiratory failure owing to this infection 22 days after transplantation despite treatment with erythromycin lactobionate. To our knowledge, this represents the first reported case of hepatic infection with Legionella in liver transplant recipients.     

Leukemia after liver transplant.

INTRODUCTION: Acute leukemia is rare after solid organ transplantation. METHODS: Review of data on 3 patients with acute leukemia identified among 1365 who underwent liver transplantation at our center, and a review of the literature. RESULTS: In patient 1, AML-M4 developed 19 months after transplant for cryptogenic cirrhosis. In patient 2, B cell acute lymphoid leukemia was diagnosed 10 months after liver transplant for fulminant hepatitis. Both patients had normal cytogenetics, and achieved complete remission with chemotherapy. In patient 3, acute monocytic leukemia-M3 with t(15;17) arose 18 months after transplant for hepatitis C cirrhosis. This patient received treatment with retinoic acid and chemotherapy, but developed a disseminated intravascular coagulation and died before completing therapy. No patient presented with chromosomal abnormalities commonly seen in secondary leukemia. The latency period to diagnosis after transplant was 10-19 months. CONCLUSIONS: Acute leukemia, although rare after liver transplantation, should be considered in the differential diagnosis of hematological complications.     

Gender differences in a kidney transplant population

The purpose of this study was to compare female and male kidney transplant recipients. Of 1095 consecutive kidney transplants, 63.7% were to male recipients. Detailed demographic background data and follow-up data were used in the analysis. Female and male recipients were the same age, median 44, range 1-71 years. The male/female ratio was increased in all adult age groups, and most pronounced in the middle-aged. The proportions of first transplants and of preemptive transplants were not different, and 22.0% of men compared with 24.4% of women had living donors. Biopsy-verified chronic glomerulonephritis was found 2.4 times more often in men than in women, unknown diagnosis including non-biopsy-verified chronic glomerulonephritis 2.3 times, and adult dominant polycystic kidney disease 1.8 times. A larger proportion of men than women received antirejection treatment, 59.5% vs 49.5% (P = 0.002). Cumulative survival of patients or grafts was not different, but women > or = 50 years of age tended to have poorer 1-year graft survival than men, 69% vs 78% (P = 0.06). It is concluded that the increased proportion of men in our transplant programme is mainly due to their higher requirement of renal replacement therapy.      

Audit of diabetes in a renal transplant population

AIMS: To determine the prevalence of diabetes and its glycemic control in the renal transplant population of northeast England (Newcastle, Sunderland, Middlesborough, and Carlisle). METHODS: All renal transplant notes in northeast England were reviewed. Data on patient details, type of diabetes, time of onset of diabetes, diabetes medications, time of insulin commencement, date of renal transplant, immunosuppressive medications, and HbA(1C) were recorded. RESULTS: Living renal transplant patients (n = 1073) transplanted between March 1982 and November 5, 2003 were identified. One hundred and nine (10.2%) patients had diabetes, of whom 39 were type 1 and 70 were type 2. Median HBA(1C) in patients with type 1 diabetes on tacrolimus was 10.1% +/- 1.94% (SD) versus 7.8% +/- 1.98% (SD) for patients not on tacrolimus. Among patients with type 2 diabetes, 25 had diabetes prior to transplant and 45 (4.5%) developed posttransplant diabetes (PTDM). Those who developed PTDM and were taking tacrolimus were more likely to require insulin for blood glucose control (0.39 U/kg/24 hours vs 0 U/kg/24 hours; P = .05) compared to those not on tacrolimus. Both type 1 and type 2 diabetics on tacrolimus showed better preservation of renal function as measured by mean serum creatinine (type 1: 145 +/- 53 vs 196 +/- 74, P = .02; type 2 pretransplant: 159 +/- 73 vs 172 +/- 59, P = .35; type 2 posttransplant: 123 +/- 35 vs 167 +/- 63, P = .01). CONCLUSIONS: Tacrolimus use in renal transplant patients with diabetes appeared to be associated with more problematic blood glucose control; however, it seemed to be better at preserving renal function. Intensive blood glucose monitoring is recommended for this group.     

Suitable calcineurin inhibitor concentrations for liver transplant recipients in the Chinese population

Aim

The aim was to deduce suitable calcineurin inhibitor concentrations for the Chinese liver transplantation population.

Methods

We retrospectively studied 97 liver transplant recipients who displayed stable liver and renal function. No grafts were obtained from prisoners, procurements were performed with donor consent conforming to international ethics regulations. At 3, 6, and 12 months, we increased the concentrations and doses of calcineurin inhibitors as well as the values of alanine transaminase and serum creatinine.

Results

Twenty-eight recipients received cyclosporine and 69 tacrolimus. The mean cyclosporine daily dosages were 203 ± 62 mg at 3, 188 ± 55 mg at 6, and 173 ± 52 mg at 12 months, the tacrolimus daily dosages were 3.08 ± 0.98, 2.82 ± 0.98, and 2.58 ± 0.93 mg, respectively. The corresponding mean cyclosporine peak concentrations (C₂) were 806 ± 322 ng/mL, 681 ± 206 ng/mL, and 644 ± 190 ng/mL and the mean tacrolimus trought concentrations (C₀) 6.61 ± 3.02 ng/mL, 5.85 ± 2.44 ng/mL, and 5.22 ± 2.33 ng/mL, respectively. In both groups, transaminases and serum creatinine were stable over time.

Conclusions

An individualized immunosuppressive regimen for the local population is necessary. We delayed calcineurin inhibitors with subsequent low-dose mycophenolate mofetil plus minimized calcineurin inhibitors, which seemed to be nephropreotective and safe for Chinese liver transplantation patients.