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Biomedical subjects

Michael R Lucey

Publications and source records attributed to Michael R Lucey.

At least 19 recordsLinked to original sources

Hepatitis C in transplant recipients of solid organs, other than liver.

Hepatitis C virus (HCV) infection is prevalent in candidates for, and recipients of, solid organ transplants. HCV infection can lead to diminished patient and allograft survival in the long-term in recipients of kidney transplants. Outcomes in recipients of other solid organ transplants (lung, heart, small bowel, pancreas, pancreas-kidney) are not well established. Large, well-designed, prospective studies are needed to answer these questions. Interferon therapy for HCV before transplantation can lead to improved outcomes. Therefore, transplant candidates should be considered for and offered interferon therapy before embarking on organ transplantation. Posttransplant interferon therapy can be complicated by acute allograft rejection and is not recommended, except with advanced liver disease.

Disease Transmission, Infectious↗

Liver transplantation: an update.

PURPOSE OF REVIEW: Recent attention in liver transplantation has focused on equity in organ allocation and management of post-transplant complications. RECENT FINDINGS: Adoption of the model for end-stage liver disease (MELD) for liver allocation has been successful in implementing a system based on medical urgency rather than waiting time. Refinements are being studied in reducing geographic disparities and improving transplant benefit by balancing pre-transplant mortality and post-transplant survival. With hepatocellular carcinoma becoming a bigger proportion of liver transplants since MELD, emerging literature is examining expansion of the current criteria for transplantation of hepatocellular carcinoma. Hepatitis C virus infection is associated with worse patient and graft survival post-transplantation than other liver diseases. The optimal timing and delivery of current antiviral therapy and immunosuppressive strategies in reducing the severity of hepatitis C virus recurrence post-transplantation are discussed. Chronic renal dysfunction after liver transplantation is a source of considerable morbidity. Nephron-sparing immunosuppression regimens are emerging with encouraging results. SUMMARY: Organ allocation tends to evolve under MELD with a focus on reducing geographic disparities and maximizing transplant benefit. Hepatitis C virus, hepatocellular carcinoma and chronic renal dysfunction are a major challenge and continued research in these areas will undoubtedly lead to better outcomes for transplant recipients.

Humans↗

Self-organizing maps can determine outcome and match recipients and donors at orthotopic liver transplantation.

BACKGROUND: There is a relative lack of donor organs for liver transplantation. Ideally, to maximize the utility of those livers that are offered, donor and recipient characteristics should be matched to ensure the best possible posttransplant survival of the recipient. METHODS: With prospectively collected data on 827 patients receiving a primary liver graft for chronic liver disease, we used a self-organizing map (SOM) (one form of a neural network) to predict outcome after transplantation using both donor and recipient factors. The SOM was then validated using a data set of 2622 patients undergoing transplantation in the United Kingdom at other centers. RESULTS: SOM analysis using 72 inputs and two survival intervals (3 and 12 months) yielded three neurons with either higher or lower probabilities of survival. The model was validated using the independent data set. With 20 patients on the waiting list and 10 sequential donor livers, it was possible to demonstrate that the model could be used to identify which potential recipients were likely to benefit most from each liver offered. CONCLUSIONS: With this approach to matching donor livers and recipients, it is possible to inform transplant clinicians about the optimum use of donor livers and thereby effectively make the best use of a scarce resource.

Comorbidity↗

Liver transplantation for HELLP syndrome.

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a rare complication of pregnancy that is associated with preeclampsia and may result in rupture of the liver. Although there have been case reports of liver transplantation for HELLP syndrome, the outcomes of transplantation for this rare indication have not been reported. Furthermore, the optimal management of complicated HELLP syndrome and indications for liver transplantation are unclear. Our objective was to review the national experience with liver transplantation for HELLP syndrome and to develop a comprehensive algorithm for the management of liver complications of HELLP syndrome, including indications for transplantation. A recent case from our institution is reported and the literature is reviewed. The results of liver transplantation for HELLP syndrome were analyzed from the United Network for Organ Sharing database. Between October 1987 and November 2003 there have been 8 deceased donor liver transplants performed for complications related to HELLP syndrome. As of the most recent follow-up, 6 of the 8 patients are alive, with both deaths occurring within 1 month of transplantation, and 2 patients have required retransplantation. This review supports that good results can be obtained with liver transplantation for patients with complicated HELLP syndrome that have either ongoing, uncontrolled hemorrhage or liver necrosis and failure. Patients with complicated HELLP syndrome are best managed at a center with expertise in liver transplantation.

Adult↗

Neuroimaging in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a poorly defined, complex neuropsychological disorder that often accompanies portal hypertension. Although the mechanisms underlining HE and the characterization of HE are still under investigation, the information derived from functional neuroimaging of patients with HE complemented by laboratory investigation and neuropsychological and neurophysiological studies have clarified much of the neuroanatomical defects. In this review, we have provided an outline of the understood mechanisms of HE and the associated findings on neuroimaging.

Ammonia↗

Liver transplantation in alcoholic patients.

Alcoholic liver disease is one of the most common causes of cirrhosis and indications for orthotopic liver transplantation in Europe and North America. The reluctance to transplant alcoholics stems in part from the view that alcoholics bear responsibility for their illness. There is also the perception that the alcoholic person is likely to relapse into alcohol use after transplantation and thereby damage the allograft. In this review, we considered the evaluation for and outcome of liver transplantation in alcoholics with special attention to the specific risks of alcohol relapse, to show that alcoholism should be considered like other co-morbid states rather than as a moral flaw.

Acute Disease↗

A comparison of tacrolimus and cyclosporine in liver transplantation: effects on renal function and cardiovascular risk status.

A retrospective chart review of 1065 consecutive liver allograft recipients in 11 centers from January 1997 to September 1998 was performed. Patients were followed for 3 years or until graft loss. Patients received either tacrolimus (n = 594), cyclosporine (n = 450) or no calcineurin inhibitor (n = 21). Model for end-stage liver disease (MELD) scores at time of transplant were similar between the two groups. During follow-up, more patients switched from cyclosporine to tacrolimus (26.7%) than from tacrolimus to cyclosporine (12.8%; p < 0.0001). Patient and graft survival were equivalent. Corticosteroid use was more common in cyclosporine-treated patients (p < 0.00001). Patients receiving tacrolimus experienced lower serum creatinine levels at months 3 through 36 (p < 0.0001). Systolic blood pressure was lower in patients receiving tacrolimus (p < 0.001) despite a reduced requirement for anti-hypertensive agents (p < 0.0001). In addition, tacrolimus was associated with lower total cholesterol and triglyceride levels for months 3 through 24 and 3 through 12, respectively (p < 0.01), despite a reduced requirement for anti-hyperlipidemic agents. The incidence of new-onset diabetes mellitus was similar in both groups. While both calcineurin inhibitors were associated with excellent patient and graft survival, renal function, blood pressure and serum lipid levels were significantly better with tacrolimus treatment.

Adolescent↗

Infected bilomas in liver transplant recipients: clinical features, optimal management, and risk factors for mortality.

BACKGROUND: Infected hepatic fluid collections (bilomas) are a major infectious complication of liver transplantation. Limited data exist on management and outcome of biloma. METHODS: We report a cohort study of 57 liver transplant recipients with posttransplantation bilomas undertaken to identify the clinical features of biloma, management strategies, and outcome. RESULTS: Fever (44%) and abdominal pain (40%) were the most common presenting symptoms, but one-third of patients were asymptomatic; 79% had elevated hepatic enzyme levels. Patients without hepatic artery thrombosis (HAT) had the highest rates of resolution with percutaneous drainage and anti-infective therapy (64%). Retransplantation was necessary in 64% of patients with HAT and biloma. Independent predictors of resolution with nonsurgical therapy were absence of HAT (odds ratio [OR] 7.69; P=.01) and absence of Candida (OR, 9.09; P=.02) or enterococcal infection (OR, 7.69; P=.03). Patients with bilomas had significantly greater mortality (Cox proportional hazard ratio [HR], 2.38; P=.008, by log rank test) and graft loss (HR, 4.31; P<.0001). Predictors of mortality by multivariable analysis included renal insufficiency (OR, 12.51; P=.02) or infection with Candida species (OR, 4.93; P=.03) or gram-negative bacilli (OR, 9.12; P=.01). CONCLUSION: Posttransplantation biloma should be suspected in patients with fever or abdominal pain or abnormalities of hepatic enzymes, and it can be confirmed by computerized tomography and radiographically guided aspiration. Bilomas are most likely to be successfully treated nonsurgically in patients without HAT and without Candida or enterococcus infection.

Candida↗

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

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.

Bacterial Infections↗

Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era. December 8, 2003, Washington, DC, USA.

A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document.

Adult↗

How will patients be selected for transplantation in the future?

1. The model for end-stage liver disease has become a selection tool for recipients for liver transplantation. 2. The present selection / allocation system does not recognize distinctions in "donor organ quality." 3. Many studies have shown that donor factors such as age, gender, fat content, and heart beating versus non-heart beating status influence outcome of the liver transplantation. 4. Efforts to increase organ donation are likely to provide more "expanded-criteria donors." 5. Future selection practices may attempt to match specific recipients to specific donors.

Adult↗

Model for end stage liver disease score predicts mortality across a broad spectrum of liver disease.

BACKGROUND/AIMS: The utility of the model for end stage liver disease (MELD) score in non-transplant patients, particularly in those with less severe chronic liver disease remains uncertain. We studied and compared the predictive abilities of the MELD score and the Child-Turcotte-Pugh (CTP) score for intermediate (1-year) and long-term (5-year) mortality. METHODS: One thousand six hundred and eleven patients with chronic liver disease were studied. Observed and predicted survival curves were plotted to evaluate the predictive ability of the MELD score for survival. Receiver operating characteristic (ROC) curves was used to compare the MELD and CTP score. A multivariable model was constructed to examine predictors of mortality. RESULTS: The MELD score was a good predictor of 1-year mortality in chronic liver disease (c-statistics for all subgroups >/=0.75) and of 3- and 6-month mortality in alcoholic hepatitis (c-statistic >/=0.83). The CTP score had similar predictive abilities as the MELD. Hepatic encephalopathy was a strong independent predictor of death (Hazard ratio-2.8, P<0.0001). CONCLUSIONS: The MELD score is a valid prognostic score for intermediate term mortality in a heterogeneous population with chronic liver disease although the CTP score is equivalent in predicting survival. Inclusion of hepatic encephalopathy adds additional prognostic value to the MELD score.

Female↗

The prevalence of alcohol-induced liver disease and hepatitis C and their interaction in a tertiary care setting.

BACKGROUND & AIMS: We examined the prevalence and clinical characteristics of alcohol-induced liver disease (ALD) in patients referred to a tertiary care center and examined the interaction between ALD and hepatitis C virus (HCV) in a longitudinal survival model. METHODS: A total of 1611 patients with chronic liver disease referred to a tertiary care center between 1994 and 2001 were analyzed. The survival of ALD, HCV, and the combination of the 2 (ALD + HCV) was compared in cirrhotic and precirrhotic patients by using Kaplan-Meier estimates. A Cox proportional hazards model was used to examine the independent effects of predictors on survival. RESULTS: ALD comprised 31% of the cohort, ALD + HCV comprised 14%, HCV comprised 22%, and the rest comprised 33%. The survival of precirrhotic patients with HCV was significantly better than the survival of those with ALD (hazard ratio, 0.27; P = 0.0006) over long-term and 1-year (hazard ratio, 0.24; P = 0.016) follow-up periods. There was no difference in survival between patients with ALD and ALD + HCV ( P = 0.62). In patients with cirrhosis, survival did not differ by cause; decompensated liver disease (hazard ratio, 1.67; P = 0.004) and continued alcohol abuse (hazard ratio, 2.19; P = 0.002) predicted worse survival in this group. CONCLUSIONS: ALD with HCV remains a prevalent cause of chronic liver disease in patients referred to a U.S. tertiary care center. In patients with ALD, the addition of HCV does not change survival, suggesting alcoholism is the driving force for mortality in patients coming to clinical attention. In patients with cirrhosis, ongoing excessive alcohol use and complications of end-stage liver disease drive mortality, irrespective of the underlying cause of chronic liver disease.

Age Factors↗

Immunosuppression: practice and trends.

Over the past decade, immunosuppression therapy has undergone striking changes in the scale and pace by which new immunosuppressive molecules and antibodies have become incorporated into daily transplant medicine. An organ-by-organ review of data reveals several trends. The highest use of induction therapy (over 70% of patients) was reported for simultaneous pancreas kidney (SPK) and pancreas after kidney (PAK) transplants in 2002; use of induction therapy was less common in liver transplants (only 18%). Corticosteroids served as discharge maintenance immunosuppression in over 87% of the recipients of kidney, SPK, PAK and thoracic transplants, and in over 70% of pancreas transplant alone (PTA) recipients. Corticosteroid use in intestine transplants was reported in 64% of recipients in 2002. A shift in the calcineurin inhibitor used for maintenance immunosuppression from cyclosporine to tacrolimus for the majority of patients had occurred for kidney, PAK, SPK, PTA, liver, lung, and heart-lung by 2001. For heart transplants, cyclosporine remained the calcineurin inhibitor of choice; tacrolimus remained the predominant calcineurin inhibitor agent for intestine (since 1994). Use of antibody treatment for rejection during the first post-transplant year for most organs declined. Short-term outcomes have improved, based on the observation that rates of rejection within the first year post-transplant have diminished.

Graft Rejection↗