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Biomedical subjects

R H Wiesner

Publications and source records attributed to R H Wiesner.

At least 55 records · Page 3Linked to original sources
PubMed1999

Human herpesvirus 6 seronegativity before transplantation predicts the occurrence of fungal infection in liver transplant recipients.

BACKGROUND: Invasive fungal infection has a major impact on the morbidity and mortality of liver transplant recipients. Human herpesvirus (HHV)-6 infection after transplantation is associated with an immunosuppressive state and the development of cytomegalovirus disease. Because cytomegalovirus infection is a risk factor for invasive fungal infection after transplantation, we have examined whether HHV-6 and fungal infection are associated after transplantation. METHODS: Pretransplantation sera from 247 consecutive liver transplant recipients were analyzed for IgG to HHV-6. Thirty-three (13%) HHV-6-seronegative recipients were identified. Six of 33 (18%) seronegative recipients experienced fungal infection as compared with 15 of 214 (7%) seropositive recipients (P=0.034). RESULTS: In a univariate analysis of risk factors for fungal infection, pretransplantation seronegativity to HHV-6 (P=0.034), intraoperative cryoprecipitate requirements greater than the 75th percentile (P=0.035), reoperation (P=0.005), biliary stricturing postoperatively (P=0.046), and gastrointestinal or vascular complications postoperatively (P=0.030) were identified as significant risk factors. Moreover, in pairwise multivariate analysis, pretransplantation HHV-6 seronegativity remained a significant variable even in the presence of each of the other variables. CONCLUSIONS: These results suggest that HHV-6 seronegativity before transplantation is a valuable clinical marker that identifies patients at risk for developing fungal infection after transplantation.

Disease-Free Survival↗
PubMed1999

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↗
PubMed1999

Recurrent and new hepatitis C virus infection after liver transplantation.

Chronic infection with the hepatitis C virus (HCV) is the most common reason for liver transplantation. We examined the results of laboratory tests for HCV on a cohort of patients who received a liver transplant between 1990 and 1994 at three large centers. Seven hundred twenty-two recipients and 604 donors were tested for antibody to HCV (anti-HCV) using a second-generation enzyme-linked immunoassay (EIA-2), followed by recombinant immunoblot (RIBA-2) and HCV RNA confirmation by reverse-transcription polymerase chain reaction (RT-PCR) (with genotyping and viral quantification). Diagnosis of posttransplantation infection required detection of serum HCV RNA that could be genotyped by sequencing or was repeatedly positive despite being unsequenceable. Twenty-five percent of transplantation candidates were seropositive for anti-HCV. Approximately 86% of anti-HCV-positive, 93% of RIBA-positive, and 97% of HCV RNA-positive candidates developed infection after transplantation. Pretransplantation HCV RNA was superior to RIBA-2 for predicting posttransplantation infection. Whereas HCV genotype was identified in nearly all candidates and changed little after transplantation, serum viral levels rose markedly after transplantation. Fifteen donors were either anti-HCV- or HCV RNA-positive. Recipients of grafts from donors with HCV RNA all developed infection, whereas infection was not detected in recipients of grafts from donors with anti-HCV but without detectable HCV RNA. The rate of new infection fell significantly (P =.02) after the introduction of EIA-2 screening of blood. Donor and candidate markers for HCV predict posttransplantation infection.

Cohort Studies↗
PubMed1999

Recurrence of primary sclerosing cholangitis following liver transplantation.

Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been suggested; however, it has not been fully defined because of numerous complicating factors and the lack of diagnostic criteria. In the present study, we investigated the recurrence of PSC by developing strict criteria and applying them to a large cohort of PSC patients who underwent liver transplantation. Between March 1985 and June 1996, 150 PSC patients underwent liver transplantation at the Mayo Clinic; mean follow up was 55 months. The incidence of nonanastomotic biliary strictures and hepatic histologic findings suggestive of PSC were compared between patients transplanted for PSC and a non-PSC transplant control group. Our definition of recurrent PSC was based on characteristic cholangiographic and histologic findings that occur in nontransplant PSC patients. By using strict criteria, 30 patients with other known causes of posttransplant nonanastomotic biliary strictures were excluded leaving 120 patients for analysis of recurrence of PSC. We found evidence of PSC recurrence after liver transplantation in 24 patients (20%). Of these, 22 out of 24 patients showed characteristic features of PSC on cholangiography and 11 out of 24 had compatible hepatic histologic abnormalities with a mean time to diagnosis of 360 and 1,350 days, respectively. Both cholangiographic and hepatic histologic findings suggestive of PSC recurrence were seen in nine patients. The higher incidence and later onset of nonanastomotic biliary strictures in patients with PSC compared with a non-PSC control group is supportive of the fact that PSC does recur following liver transplantation. We were unable to identify specific clinical risk factors for recurrent PSC, and the overall patient and graft survival in patients with recurrent PSC was similar to those without evidence of recurrence. Our observations provide convincing evidence that PSC frequently recurs in the hepatic allograft using strict inclusion and exclusion criteria.

Adult↗
PubMed1999

The relative role of the Child-Pugh classification and the Mayo natural history model in the assessment of survival in patients with primary sclerosing cholangitis.

The Child-Pugh classification is a simple, convenient prognostic measure in patients with liver cirrhosis. We investigated the relative role of the Child-Pugh classification and the Mayo model in the assessment of survival in patients with primary sclerosing cholangitis (PSC). Of the 173 patients described in the original Mayo PSC natural history model, 147 patients had sufficient information in the medical record to allow computation of the Child-Pugh score. We used our most recent modification of the Mayo model to compute the risk score, based on patient's age, serum levels of bilirubin, albumin, and aspartate aminotransferase and history of variceal bleeding. Using the risk score (R), patients were divided into the low- (R < 0), intermediate- (0 </= R < 2), and high-risk (R >/= 2) groups. Kaplan-Meier estimates and proportional hazards analysis were used to evaluate the two prognostic models. Although there was a statistically significant correlation between the Child-Pugh and Mayo risk scores, two-thirds of the patients had a Child-Pugh score of 5 or 6 and a relatively wide range of risk scores (-1.1-4.3). The probability of survival for 7 years in patients in the low-, intermediate-, and high-risk groups was 92%, 74%, and 40% for Child-Pugh class A (n = 96) and 100%, 62%, and 28% for Child-Pugh class B patients (n = 44), respectively. There were only a small number (n = 7) of Child-Pugh class C patients. In our age-adjusted multivariate analysis, each unit increase in the Mayo risk score was associated with a 2.5-fold increase in the risk of death (95% confidence interval: 1.8-3.4, P <.01), whereas Child-Pugh classification had no significant impact on survival (Child-Pugh B vs. A: risk ratio = 1.1 [95% confidence interval: 0.6-2.0]; Child-Pugh C versus A: risk ratio = 0.6 [95% confidence interval: 0. 2-1.8]). In contrast to the Child-Pugh classification, which was developed for advanced liver cirrhosis, the Mayo model provides valid survival information, particularly in patients early in the course of PSC.

Adult↗
PubMed1999

Hepatic retransplantation in cholestatic liver disease: impact of the interval to retransplantation on survival and resource utilization.

The aim of our study was to quantitatively assess the impact of hepatic retransplantation on patient and graft survival and resource utilization. We studied patients undergoing hepatic retransplantation among 447 transplant recipients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) at 3 transplantation centers. Cox proportional hazards regression analysis was used for survival analysis. Measures of resource utilization included the duration of hospitalization, length of stay in the intensive care unit, and the duration of transplantation surgery. Forty-six (10.3%) patients received 2 or more grafts during the follow-up period (median, 2.8 years). Patients who underwent retransplantation had a 3.8-fold increase in the risk of death compared with those without retransplantation (P <.01). Retransplantation after an interval of greater than 30 days from the primary graft was associated with a 6.7-fold increase in the risk of death (P <.01). The survival following retransplantations performed 30 days or earlier was similar to primary transplantations. Resource utilization was higher in patients who underwent multiple consecutive transplantations, even after adjustment for the number of grafts during the hospitalization. Among cholestatic liver disease patients, poor survival following hepatic retransplantation is attributed to late retransplantations, namely those performed more than 30 days after the initial transplantation. While efforts must be made to improve the outcome following retransplantation, a more critical evaluation may be warranted for late retransplantation candidates.

Adult↗
PubMed1999

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension.

Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as "portopulmonary hypertension." Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension. Using right-heart catheterization, we evaluated the acute pulmonary hemodynamic effects of intravenous epoprostenol in patients with moderate to severe pulmonary hypertension (mean pulmonary artery pressure [MPAP] >/=35 mm Hg) associated with clinical manifestations of portal hypertension. Effects of long-term infusion of epoprostenol were also evaluated. We studied 15 consecutive patients with portopulmonary hypertension; 14 underwent acute administration of epoprostenol, and no significant side effects were noted. Ten patients received continuous epoprostenol (range, 8 days-30 months). Acute changes in PVR (-34% +/- 18%), MPAP (-16% +/- 10%), and cardiac output (CO) (+21 +/- 18%), were statistically significant (P <.01). Long-term use of epoprostenol further lowered PVR (-47% +/- 12% from baseline and -31% +/- 22% from the acute change; P <.05) in the 6 patients restudied by right-heart catheterization. Death occurred in 6 of 10 (60%) of those receiving long-term epoprostenol. In moderate to severe portopulmonary hypertension, intravenous epoprostenol resulted in a significant improvement (both acute and long-term) in PVR, MPAP, and CO. Potential adverse effects on portal hypertension and implications for orthotopic liver transplantation (OLT), however, require further study.

Adult↗
PubMed1999

Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis.

Liver transplantation is the only effective therapeutic option for patients with end-stage liver disease due to primary sclerosing cholangitis (PSC). In this study, we analyzed a single center's experience with 150 consecutive PSC patients who received 174 liver allografts. Mean follow-up was 55 months. Actuarial patient survival at 1, 2, 5, and 10 years was 93.7%, 92.2%, 86.4%, and 69.8%, respectively, whereas graft survival was 83.4%, 83.4%, 79.0%, and 60. 5%, respectively. The main indication for retransplantation was hepatic artery thrombosis, and the major cause of death was severe infection. Patients with PSC had a higher incidence of acute cellular and chronic ductopenic rejection compared to a non-PSC control group. Chronic ductopenic rejection adversely affected patient and graft survival. Biliary strictures, both anastomotic and nonanastomotic, were frequent and occurred in 16.2% and 27.2% of patients, respectively. The incidence of recurrent PSC was 20%. A negative impact on patient survival was not seen in patients with either postoperative biliary strictures or recurrence of PSC. Six patients (4%) had cholangiocarcinoma and 1 patient died related to recurrence of malignant disease. Seventy-eight percent of PSC patients had associated inflammatory bowel disease, most commonly chronic ulcerative colitis, which did not adversely impact patient outcome posttransplantation. Nine patients required proctocolectomy after liver transplantation; 5 because of intractable symptoms related to inflammatory bowel disease and 4 due to the development of colorectal carcinoma/high-grade dysplasia. Our data show that liver transplantation provides excellent long-term patient and graft survival for patients with end-stage PSC.

Cause of Death↗
PubMed1999

CD40L (CD154) expression in human liver allografts during chronic ductopenic rejection.

The CD40-CD40L (CD154) interaction plays a pivotal role in the effector mechanisms of allograft rejection. Blockade of the CD40/CD40L costimulatory pathway prevents the development of chronic allograft rejection in several animal transplant models. The relevance of in situ CD40 and CD40L expression in human liver allografts was assessed by immunohistochemistry during ductopenic chronic rejection (CR). In CR allograft specimens (n = 8), marked CD40L expression was detected on Kupffer cells (KCs) and sinusoidal macrophages with a unique centrilobular distribution (P <.001). The CD40L+ KCs and macrophages were shown to be CD68+ after immunohistochemical analysis of serial sections with anti-CD68 monoclonal antibody. Moderate staining of vascular and sinusoidal endothelial cells and mononuclear infiltrates was observed in some CR cases. These findings were in contrast to the absence of CD40L expression in controls (n = 11) consisting of stable liver allograft and normal liver tissue specimens. Only occasional CD40 expression in some cases of CR and controls was observed. In CR, CD40L (CD154) expression is manifested on KCs and macrophages. The present novel data show another important cellular source of CD40L expression and suggest a potential role of KCs/macrophages and CD40/CD40L costimulatory interactions in the pathogenesis of chronic rejection ductopenic liver allograft.

CD40 Antigens↗
PubMed1999

Preoperative hepatic artery chemoembolization followed by orthotopic liver transplantation for hepatocellular carcinoma.

In our experience, the primary obstacle precluding the widespread use of orthotopic liver transplantation (OLT) for definitive therapy of hepatocellular carcinoma (HCC), even for early-stage disease, is preventing tumor recurrence. Chemoembolization is an attractive strategy to minimize tumor progression before OLT because of its shown antitumor effect, ability to be repeated, and minimal systemic toxicity. Thus, this pilot study was undertaken to determine the tolerability and treatment outcomes of pretransplantation chemoembolization of HCC followed by OLT. Between 1992 and 1997, 27 patients with HCC who had cirrhosis, no extrahepatic metastasis, less than three tumor nodules of less than 5 cm each, and no evidence of vascular invasion on preoperative imaging studies were enrolled onto the protocol. Chemoembolization was performed using Ivalon particles with mitomycin, doxorubicin, and cisplatin. Twenty-four patients completed the protocol with chemoembolization and a liver transplant. The mean United Network of Organ Sharing waiting time was 167 days. Chemoembolization was well tolerated. On examination of the explanted liver, the majority of patients had a single lesion, mean tumor size was 3.66 cm (range, 1.5 to 6 cm), and the majority of patients had stage II disease. None of the transplant recipients has developed recurrent HCC (mean follow-up, 29.2 months; range, 9 to 55 months). The 1- and 2-year disease-free survival rates are 91% and 84%, respectively. In conclusion, chemoembolization followed by OLT is well tolerated and associated with excellent outcomes in selected patients with HCC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Late recurrence and rapid evolution of severe hepatopulmonary syndrome after liver transplantation.

Recurrence of hepatopulmonary syndrome (HPS) after orthotopic liver transplantation (OLT) in an adult has never been reported. We describe a 23-year-old woman who initially underwent OLT because of debilitating and severe HPS associated with nonalcoholic steatohepatitis (NASH). Although the clinical resolution of HPS was well documented day 117 post-OLT, the reappearance of NASH was documented by liver biopsy. Severe hypoxemia because of recurrent HPS rapidly evolved beginning approximately day 700 post-OLT. Retransplantation was attempted, but the patient died post-OLT of sepsis and/or multiorgan failure.

Acute Disease↗
PubMed1999

Evolving concepts in the diagnosis, pathogenesis, and treatment of chronic hepatic allograft rejection.

Chronic hepatic allograft rejection is characterized by the histological findings of ductopenia and a decreased number of hepatic arteries in portal tracts in the presence of foam cell (obliterative) arteriopathy. Recent studies have extended the histological spectrum of chronic rejection to include the presence of biliary epithelial atrophy or pyknosis involving the majority of small ducts present in the liver biopsy specimen. Overall, the incidence of chronic rejection in adults appears to be decreasing and is currently approximately 4%. However, the incidence of chronic rejection in pediatric liver transplant recipients has been more stable and ranges from 8% to 12% in most studies. Clinical risk factors associated with chronic rejection include: underlying liver disease, HLA donor-recipient matching, positive lymphocytotoxic cross-match, cytomegalovirus infection, recipient age, donor-recipient ethnic origin, male donor into female recipient, number of acute rejection episodes, histological severity of acute rejection episodes, low cyclosporine trough levels, and retransplantation for chronic rejection. Chronic rejection, once diagnosed, frequently leads to graft failure; however, a number of reports indicated 20% to 30% of the patients with this diagnosis may respond to additional immunosuppressive therapy or even resolve spontaneously receiving baseline immunosuppression. Newer immunosuppressive agents, such as tacrolimus and mycophenolate, may successfully reverse chronic rejection, particularly when it is diagnosed in its early histological stages.

Adult↗
PubMed1999

Etiology and natural history of primary sclerosing cholangitis.

The etiology of primary sclerosing cholangitis remains unknown. Bacteria, toxins, viral infections, and immunological and genetic factors have all been proposed as etiological agents. Portal bacteremia, toxins absorbed from the diseased colon in inflammatory bowel disease, and cytomegalovirus and reovirus infections have been implicated by various investigators but there is little evidence to support these hypotheses. The close association between primary sclerosing cholangitis and various human leukocyte antigen haplotypes is now well established and lends support to the theory that immunologic and genetic mechanisms may be involved in its pathogenesis. Patients with primary sclerosing cholangitis may have elevated levels of circulating immune complexes, immunoglobulins, and non-organ specific autoantibodies. The association between ulcerative colitis and primary sclerosing cholangitis remains unexplained and both groups of patients have a high prevalence of antibodies to the perinuclear cytoplasmic antigen. The long-term prognosis in primary sclerosing cholangitis is tempered by the development of cholangiocarcinoma in 6%-30% of patients when followed over long periods of time. Detecting cholangiocarcinoma early in a patient with primary sclerosing cholangitis is one of the most frustrating problems faced by a clinician while caring for these patients. The long-term outlook for patients with primary sclerosing cholangitis and cholangiocarcinoma remains dismal, whatever the treatment modality employed. However, the development of a multivariate statistical survival model from long-term survival data from the Mayo Clinic and other centers has been a major step in identifying individual primary sclerosing cholangitis patients at low, moderate, and high risk of dying. Such models have been useful for stratifying patients in therapeutic trials, for in patient counseling, and in patient selection and timing of liver transplantation.

Cholangitis, Sclerosing↗
PubMed1999

Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery.

BACKGROUND: Patients with cirrhosis have a reduced life expectancy. Anesthesia and surgery have been associated with clinical decompensation in patients with cirrhosis. METHODS: The authors retrospectively reviewed the records of all patients with the diagnosis of cirrhosis who underwent any surgical procedure under anesthesia at their institution between January 1980 and January 1991 (n = 733). Univariate and multivariate analyses were used to identify the variables associated with perioperative complications and short- and long-term survival. RESULTS: The perioperative mortality rate (within 30 days of surgery) was 11.6%. The perioperative complication rate was 30.1%. Postoperative pneumonia was the most frequent complication. Multivariate factors that were associated with perioperative complications and mortality included male gender, a high Child-Pugh score, the presence of ascites, a diagnosis of cirrhosis other than primary biliary cirrhosis (especially cryptogenic cirrhosis), an elevated creatinine concentration, the diagnosis of chronic obstructive pulmonary disease, preoperative infection, preoperative upper gastrointestinal bleeding, a high American Society of Anesthesiologists physical status rating, a high surgical severity score, surgery on the respiratory system, and the presence of intraoperative hypotension. CONCLUSION: Risk factors have been identified for patients with cirrhosis who undergo anesthesia and surgery.

Adolescent↗
PubMed1999

The clinical significance of simultaneous infection with hepatitis G virus in patients with chronic hepatitis C.

OBJECTIVES: Hepatitis G virus (HGV) is a recently discovered member of the flavivirus family that has been associated with acute and chronic hepatitis. HGV infection has been reported to coexist in 10-20% of patients with chronic hepatitis C. The significance of simultaneous infection with HGV and hepatitis C virus (HCV) remains to be clarified, as do the effects on HGV of therapeutic interventions such as interferon treatment or liver transplantation. THE AIMS OF OUR STUDY WERE: 1) to examine the frequency of HGV infection in the settings of liver transplantation and interferon therapy for hepatitis C; and 2) to compare HGV RNA levels before and after liver transplantation or interferon treatment. METHODS: Pre-treatment sera were available in 65 patients with chronic hepatitis C treated with interferon; pretransplant sera were available in 49 patients transplanted for end stage liver disease associated with chronic hepatitis C. Information collected included age, sex, risk factors for hepatitis, concurrent liver disease, patient and allograft survival, biochemical response to interferon, histological activity index, and degree of fibrosis/cirrhosis. HCV genotyping was performed by sequencing the NS-5 region. HGV quantitation was performed using a research-based branched DNA (bDNA) assay with a set of probes directed at the 5' untranslated region. RESULTS: HGV was detected in 10 of 49 patients (20%) before transplant and in 13 of 65 patients (20%) treated with interferon. There was a female predominance among HGV-positive compared with HGV-negative transplant patients (80% vs 20%; p < 0.01), but such a difference was not observed in the interferon-treated group. Hepatic iron concentration was lower in hepatic explants from patients who were HGV-positive than in those who were HGV-negative (318 +/- 145 microg/g dry weight vs 1497 +/- 2202 microg/g dry weight; p = 0.02). HCV exposure after 1980 was more common in the HGV-positive patients than in those who were HGV-negative for the entire study population (10 of 20 [50%] vs 16 of 66 [24%]; p = 0.03), as well as for the nontransplant subgroup (8 of 12 [67%] vs 12 of 39 [31%]; p = 0.03). HGV RNA levels declined at 1 yr after transplant in seven of eight patients. Among nine patients tested during or after interferon treatment, HGV RNA levels declined from pretreatment levels in all and disappeared in three. CONCLUSIONS: Among patients with chronic hepatitis C treated with either interferon or liver transplantation, the frequency of coinfection with HGV is about 20%. HGV may be a more recent virus in the US than HCV. Coinfection with HGV does not appear to affect the likelihood of response to interferon in patients with hepatitis C. Finally, HGV RNA levels appear to decline after both liver transplantation and interferon therapy, suggesting possible suppression by increased HCV replication in the former case, and a possible drug treatment effect in the latter.

Adult↗
PubMed1999

Methods to estimate and analyze medical care resource use. An example from liver transplantation.

This paper describes a method to construct a standardized health care resource use database. Billing and clinical data were analyzed for 916 patients who received liver transplantations at three medical centers over a 4-year period. Data were checked for completeness by assessing whether each patient's bill included charges covering specified dates and for specific services, and for accuracy by comparing a sample of bills to medical records. Detailed services were matched to a standardized service list from one of the centers, and a single price list was applied. For certain services, clinical data were used to estimate service use or, if a match was not possible, adjusted charges for the services were used. Twenty-three patients were eliminated from the database because of incomplete resource use data. There was very good correspondence between bills and medical records, except for blood products. Direct matches to the standardized service list accounted for 69.3% of services overall; 9.4% of services could not be matched to the standardized service list and were thus adjusted for center and/or time period. Clinical data were used to estimate resource use for blood products, operating room time, and medications; these estimations accounted for 21.3% of services overall. A database can be constructed that allows comparison of standardized resource use and avoids biases due to accounting, geographic, or temporal factors. Clinical data are essential for the creation of such a database. The methods described are particularly useful in studies of the cost-effectiveness of medical technologies.

Accounting↗
PubMed1998

A long-term comparison of tacrolimus (FK506) versus cyclosporine in liver transplantation: a report of the United States FK506 Study Group.

BACKGROUND: The long-term (5 year) efficacy and safety of tacrolimus (FK506) and cyclosporine were compared in primary liver transplant recipients who participated in a 1-year randomized, multicenter trial and a 4-year follow-up extension study. METHODS: A total of 529 patients (263 tacrolimus group, 266 cyclosporine group) were randomized to study drug. Patients were evaluated at 3-month intervals. Patient and graft survival rates, incidence of adverse events, and changes in laboratory and clinical profiles were determined. RESULTS: Cumulative 5-year patient and graft survival rates were comparable for the tacrolimus (79.0%, 71.8%) and cyclosporine (73.1%, 66.4%) groups. However, patient half-life survival was longer for tacrolimus-treated patients (25.1+/-5.1 years versus 15.2+/-2.5 years; P=0.049). Improved patient survival with tacrolimus was also observed for hepatitis C-positive patients (78.9% tacrolimus group versus 60.5% cyclosporine group; P=0.041). Both treatments were associated with a low incidence of late acute rejection, late steroid-resistant rejection, and death or graft loss related to rejection. Both treatments demonstrated an acceptable safety profile with maintenance of adequate renal and liver function and a low incidence of malignancy/lymphoproliferative disease and serious infections. CONCLUSIONS: Tacrolimus is a safe and effective long-term maintenance immunosuppressive agent in primary liver transplantation.

Adolescent↗