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Biomedical subjects

M F Levy

Publications and source records attributed to M F Levy.

At least 19 recordsLinked to original sources

MELD scores do not predict patient morbidity while on the liver transplant waiting list.

The goals of this study were to assess waitlist morbidity in terms of the frequency of health care services utilized by patients while on the liver transplant (LTX) waiting list and to determine whether that utilization can be predicted by the Model for End-Stage Liver Disease (MELD). Sixty-three noncomatose subjects were followed from waitlist placement until death, change in status, LTX, or study discontinuance. Health care events included doctor/clinic visits, labs, outpatient/inpatient tests and procedures, and hospital/intensive care unit days. Listing MELD scores and LTX MELD scores were examined against the number of health care event occurrences within 60 days of listing and 60 days of LTX, respectively, as were changes in MELD scores between listing and LTX and differences in the number of occurrences between the two time points. The only significant correlations noted were between LTX MELD scores and number of hospital days near LTX (r = .360, P = .046) and between LTX MELD scores and the sum total number of occurrences near LTX (r = .370, P = .044). These results suggest that MELD scores do not appear to predict morbidity in terms of health care utilization in patients awaiting LTX. Developing a system capable of predicting waitlist morbidity may lead to the implementation of medical interventions aimed at circumventing foreseeable complications and/or crises in patients awaiting LTX.

Humans↗

Sirolimus conversion after liver transplantation: improvement in measured glomerular filtration rate after 2 years.

METHODS: We reviewed our prospectively maintained database of 2005 liver transplantations. Therapy was either started de novo or converted from calcineurin inhibitors (CNIs) to sirolimus as the main immunosuppressive agent for nephrotoxicity or rejection. Glomerular filtration rate (GFR) was determined with iodine 125-labeled sodium isthalamate (Glofil-125), and serum creatinine concentration was obtained before and 3 months after transplantation, and yearly in both groups. Sirolimus levels were 10 to 15 ng/mL in patients at less than 3 months after transplantations and 5 to 10 ng/mL in the remaining patients. All patients received mycophenolate mofetil as maintenance therapy. RESULTS: Data for 29 patients in the de novo group and 35 in the conversion group were reviewed. Patients in the de novo group demonstrated an acute cellular rejection rate of 17.2%, 40% of which were steroid resistant. In this group, 48.2% discontinuation of sirolimus was necessary because of adverse effects. Patients in the conversion group demonstrated an acute cellular rejection rate of 2.8% and a 34.3% rate of sirolimus discontinuation. Seventeen (56.7%) patients at 1 year and 8 (44.4%) patients at 2 years demonstrated continued improvement in GFR. In the conversion group, case-control analysis did not demonstrate a significant difference in GFR and serum creatinine concentration (P > .05) at 1 and 2 years after conversion. At the time of review, no patients in the conversion group required hemodialysis. CONCLUSIONS: Conversion to sirolimus therapy is an effective strategy in improving renal function in patients with CNI-induced nephrotoxicity and can be done without increased rejection. Most of our patients (65.7%) tolerated sirolimus conversion. Of these, 56.7% and 44.4% demonstrated continued increase in GFR with the CNI-free regimen at 1 and 2 years, respectively. Long-term, large-population, prospective, randomized, controlled studies should further validate these results.

Creatinine↗

End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.

BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.

Adult↗

Renal replacement therapy and orthotopic liver transplantation: the role of continuous veno-venous hemodialysis.

BACKGROUND: The need for renal replacement therapy (RRT) either before or after orthotopic liver transplant (OLTX) has been reported to be a poor prognostic indicator for survival. Use of continuous veno-venous hemodialysis (CVVHD) for RRT has been reported in three series of OLTX patients with high 90-day mortality rates of 57-60%. We have examined our patient population to determine the effect of necessity and type of RRT on patient survival after OLTX. METHODS: We analyzed 1535 OLTX that were performed at our institution from 1985 through 1999, 1037 from 1985 to 1995 (period I) and 498 from 1996 to 1999 (period II). Combined liver-kidney transplants were excluded from analysis. Hospital dialysis unit records and a prospectively maintained database on all OLTX patients served as the source of data. Patients were classified into groups defined on whether or not they received RRT, when they received RRT, and the type of RRT. Groups were compared for preoperative intensive care unit status, time on the waiting list, laboratory variables, 90-day postoperative mortality, 1-year patient survival, and absolute survival. RESULTS: Use of RRT increased from 8.29% in period I to 12.45% in period II, along with increased median waiting times. In period I, patients receiving preoperative RRT had a 90-day mortality (0%) and a 1-year survival (89.5%) almost identical to those patients who never required RRT (1.7% and 90.6%). Patients who developed acute renal failure postoperatively requiring RRT, however, had a 90-day mortality of 28.6% and a 1-year survival of 55%. In period II, patients requiring RRT had a 90-day mortality of 39.7% and a 1-year actuarial survival of 54.5% compared with 6.9% and 88.6% in patients never requiring RRT. Patients treated with CVVHD had a 90-day mortality of 42% compared with 25% in patients treated with hemodialysis alone. However, patients receiving CVVHD both pre- and postoperatively had a 90-day mortality of 27.7% vs. 50% in those patients who only received CVVHD postoperatively. Patients who developed acute renal failure postoperatively, which required RRT, regardless of therapy, had a 1-year survival of only 41.0% compared with a 1-year survival of 73.6% in those patients started on RRT preoperatively, P=0.03. CONCLUSIONS: The need for RRT has increased along with waiting time in OLTX patients. Patients developing the need for RRT postoperatively have an increased 90-day mortality and lower 1-year survival with the highest being present in patients receiving CVVHD, which was started postoperatively. These findings may reflect a trend toward a sicker population awaiting OLTX and emphasize the negative impact of renal failure on survival after OLTX.

Acute Kidney Injury↗

Cannulation of the aorta in organ donors with infrarenal aortic pathologies.

Retrograde embolization of atherosclerotic arterial plaque remains a threat at the time of organ perfusion in elderly donors. In order to circumvent this potential procurement complication, we describe a technique with two variations. This technique allows for perfusion with UW solution without having to cannulate through severely atherosclerotic distal aortic walls.

Adenosine↗

Post-transplant lymphoproliferative syndrome in the pediatric liver transplant population.

Post-transplant lymphoproliferative disease remains a complication with a high morbidity and mortality. The present study examined 291 pediatric liver transplants performed in 263 children from October 1984 to December 1999. Post-transplant lymphoproliferative disease has an overall incidence of 12%. Tacrolimus and cyclosporine had a similar incidence of post-transplant lymphoproliferative disease. Fifty-six per cent of patients who developed post-transplant lymphoproliferative disease were Epstein-Barr virus negative at the time of transplantation. Mean time of conversion to Epstein-Barr virus positivity was 1.1 years after liver transplantation. Ten per cent of those who developed post-transplant lymphoproliferative disease never had Epstein-Barr virus detected. Mean time from Epstein-Barr virus positivity to detection of post-transplant lymphoproliferative disease was 2.68 years, and 3.13 years from liver transplantation (OLTx) to post-transplant lymphoproliferative disease. There was a 35% incidence of mortality. Deaths occurred a mean of 0.76 years after diagnosis of post-transplant lymphoproliferative disease. Most cases of post-transplant lymphoproliferative disease had extranodal location. There was one recurrence in 10% of patients, and two in 3%. All recurrent cases were seen in recipients who became Epstein-Barr virus positive after transplantation. There has been a decrease in the incidence of post-transplant lymphoproliferative disease from 15% to 9% to 4%. Post-transplant lymphoproliferative disease should be diagnosed promptly and treated aggressively. The best treatment, however, seems to be prevention, starting in the immediate postoperative period. Survivors should be monitored for both recurrence of post-transplant lymphoproliferative disease and acute cellular rejection.

Adolescent↗

The elderly liver transplant recipient: a call for caution.

OBJECTIVE: To determine whether liver transplantation is judicious in recipients older than 60 years of age. SUMMARY BACKGROUND DATA: The prevailing opinion among the transplant community remains that elderly recipients of liver allografts fare as well as their younger counterparts, but our results have in some cases been disappointing. This study was undertaken to review the results of liver transplants in the elderly in a large single-center setting. A secondary goal was to define, if possible, factors that could help the clinician in the prudent allocation of the donor liver. METHODS: A retrospective review of a prospectively maintained single-institution database of 1,446 consecutive liver transplant recipients was conducted. The 241 elderly patients (older than 60 years) were compared with their younger counterparts by preoperative laboratory values, illness severity, nutritional status, and donor age. Survival data were stratified and logistic regression analyses were conducted. RESULTS: Elderly patients with better-preserved hepatic synthetic function or with lower pretransplant serum bilirubin levels fared as well as younger patients. Elderly patients who had poor hepatic synthetic function or high bilirubin levels or who were admitted to the hospital had much lower survival rates than the sicker younger patients or the less-ill older patients. Recipient age 60 years or older, pretransplant hospital admission, and high bilirubin level were independent risk factors for poorer outcome. CONCLUSIONS: Low-risk elderly patients fare as well as younger patients after liver transplantation. However, unless results can be improved, high-risk patients older than 60 years should probably not undergo liver transplantation.

Age Factors↗

Readmission to the intensive care unit after liver transplantation.

OBJECTIVE: We undertook this study to understand the factors at our transplant center that contribute to patients' return to the ICU after their liver transplant and their initial discharge from that unit. Patients who, after liver transplantation, fail discharge from the Intensive Care Unit (ICU) and must be readmitted to that unit may well utilize many more resources than those patients who are well enough to stay out of the ICU. DESIGN: A retrospective review of a prospectively maintained liver transplant research database followed by a retrospective review of (a subgroup) patient charts and contemporaneous controls. SETTING: A large metropolitan tertiary care center and adult liver transplant center. PATIENTS: A total of 1,197 consecutive adult patients who underwent their initial liver transplantation from 1984 to 1996. INTERVENTION: Readmission to the intensive care unit after adult liver transplantation and discharge from that unit. MAIN RESULTS: Only recipient age, pretransplant synthetic function labs (protime and albumin), bilirubin levels, and intraoperative blood product requirements could be statistically linked to the group requiring ICU readmission. The primary etiology for ICU readmission was cardiopulmonary deterioration. Readmission was associated with significantly lower patient and graft survivals. A detailed review of 23 patients transplanted from October 1994 to June 1996 was made, with special emphasis on cardiopulmonary status (hemodynamics, respiratory variables, and chest radiograph findings). This subgroup was compared with 30 temporally matched controls who were not readmitted to the ICU. Intravascular fluid overload and lower inspiratory capacity were significant factors related to ICU readmission. Readmitted patients had a longer hospitalization with higher hospital charges than the control group. CONCLUSIONS: We conclude that the most important means of preventing ICU readmission in liver transplantation patients is to optimize cardiopulmonary function and status. Close monitoring of fluid balance to avoid hypervolemia is essential. Readmitted patients have a greater resource utilization and have lower survival rates.

Adult↗

Liver allotransplantation after extracorporeal hepatic support with transgenic (hCD55/hCD59) porcine livers: clinical results and lack of pig-to-human transmission of the porcine endogenous retrovirus.

BACKGROUND: Whole organ extracorporeal perfusion of a genetically modified humanized (transgenic) pig liver has been proposed as a technology that may sustain patients with severe liver failure while awaiting human liver transplantation. METHODS: We report on two cases of successful extracorporeal perfusion of a transgenic pig liver in patients awaiting transplantation for fulminant hepatic failure. The pig livers used were transgenic for human CD55 (decay-accelerating factor) and human CD59. These transgenic modifications are designed to reduce or eliminate the hyperacute rejection inherent in pig-to-primate xenotransplants. We also report on the results of serial surveillance testing for presence of the porcine endogenous retrovirus (PoERV) in these two patients. RESULTS: Extracorporeal perfusion in two patients was performed for 6.5 and 10 hr, respectively, followed by the successful transplantation of a human liver and resultant healthy patients (18 and 5 months later as of this writing). The porcine livers showed evidence of synthetic and secretory function (decreasing protime and bilirubin, bile production). Serial polymerase chain reaction analysis of these patients' peripheral blood mononuclear cells has failed to show presence of PoERV DNA sequences. CONCLUSIONS: The CD55/CD59 transgenic porcine liver appears capable of safely "bridging" a patient to liver transplantation. Human PoERV infection from these livers has yet to be demonstrated.

Adolescent↗

Comparing quality of life following liver transplantation for Laennec's versus non-Laennec's patients.

The overall success of orthotopic liver transplantation (OLTX) includes not only survival, but quality of life (QOL) as well. We studied one controversial group of OLTX recipients, patients transplanted for alcoholic liver disease (Laennec's), to determine if their post-OLTX QOL was similar to that of patients transplanted for non-alcoholic liver disease (non-Laennec's). Over a 10-yr period, patients undergoing OLTX at our institution were asked to complete a QOL questionnaire addressing a wide range of topics from demographics and employment to symptom distress/frequency, activities of daily living, and effect of loss of health on daily life. Twenty-four Laennec's and 100 non-Laennec's OLTX recipients completed the questionnaire at both their 2- and 5-yr follow-up visits at our institution. Both groups were well-matched in age, race, and patient location status at the time of OLTX. No significant differences could be detected between Laennec's and non-Laennec's scores regarding overall QOL, including one's ability to function, health perception, and self-perception at 2 and 5 years post-OLTX, and between 2 and 5 years post-OLTX. Although not between groups, a significant difference was noted regarding patients' satisfaction with life, with less satisfaction reported at the 5-yr versus the 2-yr time point post-OLTX. Rates of current/recent employment between both groups were also similar at 2 years post-OLTX, and again at 5 years post-OLTX. We conclude that overall QOL and employment levels appear similar between patients transplanted for alcoholic and non-alcoholic liver disease. This similarity appears to extend to 5 years post-OLTX.

Activities of Daily Living↗

Liver transplantation for hepatitis C: recurrence and disease progression in 300 patients.

The time progression of allograft damage in patients with recurrent hepatitis C after orthotopic liver transplantation (OLT) is not precisely determined. The aim of this analysis is to study the progression of disease recurrence and its impact on patient and graft survival. Data for 300 patients who underwent OLT for hepatitis C were analyzed regarding the incidence of histological recurrence, risk factors, immunosuppressive regimen, rejection episodes, and survival. For patients with histological recurrence, the timing and risks for disease progression were analyzed. Data for 30 patients who underwent retransplantation were studied. Histological recurrence occurred in 40.3% of patients, 27.2% of whom progressed to bridging fibrosis or cirrhosis. Eighty-seven percent of the patients experienced recurrence of disease within 24 months of OLT. Patients with histological recurrence within 6 months of OLT had an increased risk for progression to cirrhosis compared with patients with recurrence later than 6 months (risk ratio, 2.3). Recurrence within 1 year was associated with decreased patient and graft survival rates at 1 and 5 years (65.1% and 56.4% versus 80.6% and 78.4%; P =.004 and P =.0008, respectively). Patients with histological recurrence had a greater incidence of acute cellular rejection, as well as multiple episodes of rejection, steroid-resistant rejections, and greater cumulative doses of corticosteroids. Histological recurrence after OLT for hepatitis C is common and usually occurs within 2 years of OLT. Early recurrence negatively affects patient and graft survival. Host factors impacting on recurrence need further study. A relation between the hepatitis C virus, allograft rejection, and immunosuppression exists and needs investigation.

Adult↗

Animal organs for human transplantation: how close are we?

Solid organ transplantation has been, by most measures, a phenomenal success. Nonetheless, the field is plagued by extreme shortages of available organs from a very limited number of donors. One potential solution to this organ availability crisis is the use of animals as organ donors for humans (xenotransplantation). Though the concept remains theoretical, significant advances are being made in the field of genetics and in our understanding of the immunological barriers to xenotransplantation. With these advances also comes increased knowledge about the potential risks of xenotransplants, especially disease transmission. The eventual clinical application of animal-to-human transplants will require a careful, balanced appraisal of these issues.

Journal Article↗

Randomized, placebo-controlled, double-blind, multicenter trial of efficacy and safety of granulocyte colony-stimulating factor in liver transplant recipients.

BACKGROUND: Infection and rejection are two common complications after liver transplants. In a preliminary study, administration of granulocyte colony-stimulating factor (G-CSF) to liver transplant recipients was associated with a decrease in sepsis episodes, sepsis-related deaths, and rejection compared with a historical control group of patients. The purpose of this study was to evaluate further the efficacy of G-CSF in liver transplant patients in a randomized, placebo-controlled, double-blind, multicenter trial. METHODS: Adult patients with a United Network Organ Sharing classification of 1 or 2 were randomized to receive a placebo, 100 microg/day of G-CSF or 300 microg/day of G-CSF. The study drug was started preoperatively and then continued after the transplant for a maximum of 21 days. Patients were evaluated for microbiologically-documented infection, biopsy-proven rejection, number of treatments for rejection, length of stay in the intensive care unit and hospital, graft survival, death, and adverse events. RESULTS: During the first 30 days after the transplant, the median peak white blood cell count was 16.5x10(9)/L, 34.6x10(9)L, and 54.8x10(9)/L for the placebo, low-dose G-CSF, and high-dose G-CSF patients, respectively. The incidence of infection was 30% in G-CSF patients (34 of 114 patients) and 34% in placebo patients (20 of 58 patients). Except for more nosocomial pneumonias in the G-CSF patients (7 in 114 patients vs. 0 in 58 patients, P=0.056), the types of infections and causative organisms were also similar in both treatment groups. Although the number of treatments for clinically suspected or proven rejection was similar in the G-CSF and placebo patients, biopsy-proven rejection occurred more often in G-CSF patients (34 of 114 patients or 30%) than placebo patients (11 of 58 patients or 19%) (P=0.093). There were no cases of graft loss caused by rejection. G-CSF had no effect on length of stay in the intensive-care unit or hospital. There were 22 G-CSF patients (18%) and 10 placebo patients (15%) who died within 120 days after the transplant. No serious adverse events were attributed to G-CSF. CONCLUSION: Despite producing substantial increases in the white blood cell count after the transplant, G-CSF had no beneficial effects on infection, rejection, or survival in this study. Biopsy-proven rejection and nosocomial pneumonias were more common in patients treated with G-CSF compared with those taking the placebo. No serious adverse events were attributed to G-CSF.

Adolescent↗

A simple model to estimate survival after retransplantation of the liver.

To formulate a model predicting survival after liver retransplantation, we analyzed in detail the last 150 cases of hepatic retransplantation at UCLA. Cox proportional hazards regression analysis identified five variables that demonstrated independent simultaneous prognostic value in estimating patient survival after retransplantation: (1) age group (pediatric or adult), (2) recipient requiring preoperative mechanical ventilation, (3) donor organ cold ischemia > or =12 hr, (4) preoperative serum creatinine, and (5) preoperative serum total bilirubin. The Cox regression equation that predicts survival based on these covariates was simplified by assigning individual patients a risk classification based on a 5-point scoring system. We demonstrate that this system can be employed to identify a subgroup of patients in which the expected outcome is too poor to justify retransplantation. These findings may assist in the rational selection of patients suitable for retransplantation.

Adult↗

Quality of life before and after liver transplantation for cholestatic liver disease.

Liver transplantation (LT) is an established therapy for patients with end-stage primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). In this report, we describe the health status and quality of life (QOL) in patients with these cholestatic liver diseases before and after LT. A QOL questionnaire was completed by 157 adult patients with PBC or PSC before and 1 year after liver transplantation at the Mayo Clinic or Baylor University Medical Center. This questionnaire measured four aspects of QOL, including symptoms; physical, social, and emotional functioning; health perceptions; and overall QOL. Changes in these QOL parameters before and after LT were described, and regression analysis was used to assess the relationships between clinical and QOL factors. There were no differences in QOL parameters between patients with PBC and PSC. QOL following transplantation was substantially better than before transplantation. This was observed in all four aspects of QOL. The degree of improvement as measured by effect size (difference in mean scores divided by the pretransplantation standard deviation) was 0.53 for symptoms (P <.01), 1.16 for function (P <.01), 2.37 for health satisfaction (P <.01), and 1.16 for overall QOL (P <.01). Patients' overall QOL before transplantation was significantly related to subjective and objective health status indicators and clinical factors such as ascites and renal dysfunction. QOL at 1-year follow-up, however, could not be adequately predicted by the pretransplantation subjective health status and clinical factors. Patients with end-stage cholestatic disease undergoing LT experience substantial improvement in all aspects of QOL addressed in this study. The patients' QOL 1 year after LT could not be predicted by pretransplantation variables used in this study.

Adult↗