***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND The long-term complications of immunosuppressive therapy such as diabetes , hypercholesterolemia , and hypertension are a major source of morbidity in liver transplant recipients . In this prospect i ve , r and omized , open-label study we completely withdrew prednisone ( PRED ) 14 days after liver transplantation in an effort to decrease these metabolic complications . Patients were maintained on mycophenolate mofetil ( MMF ) in combination with either cyclosporine ( CsA ; Neoral formulation ) or tacrolimus ( TAC ) . Thus , we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy , toxicity , and effect on posttransplant metabolic complications . METHODS A total of 71 patients were r and omized to receive either TAC-MMF ( n=35 ) or CsA-MMF ( n=36 ) after liver transplantation and were analyzed for patient and graft survival .  Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes , hypertension , and hypercholesterolemia . RESULTS The 6-month patient survival rates were 94.4 % for CsA-MMF and 88.6 % for TAC-MMF . Corresponding 6-month graft survival rates were 88.7 % and 85.71 % with no immunologic graft losses in either group . The incidence of biopsy-proven acute rejection was 46 % for CsA-MMF and 42.3 % for TAC-MMF . Six patients were converted from CsA to TAC ( four for recurrent rejection ) and seven patients were converted from TAC to CsA ( four for neurotoxicity ) . Only one patient ( in the TAC-MMF group ) developed new-onset posttransplant diabetes . In contrast , four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant . The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group ( 145.2+/-41.8 mg/dl and 190.3+/-62.2 , respectively ; P<0.001 ) and the incidence of hypertension was lower in the TAC-MMF group ( 12 % vs. 30.3 % in the CsA-MMF group , P<0.01 ) . Both groups had a lower incidence of metabolic complications compared with a historical group ( n=100 ) maintained on CsA and PRED ( 10 mg/day at 6 months ) . CONCLUSIONS MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses . Early PRED withdrawal decreases posttransplant diabetes , hypercholesterolemia , and hypertension , but patients maintained on TAC  have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients BACKGROUND Results of studies in adult recipients of liver allograft suggest that tacrolimus is more efficacious than ciclosporin microemulsion in the prevention of acute rejection . We aim ed to compare these drugs in children undergoing liver transplantation . METHODS This 12-month multicentre , open-label , parallel-group , r and omised study compared a dual tacrolimus regimen ( tacrolimus/corticosteroids , n=93 ) with a triple ciclosporin microemulsion regimen ( ciclosporin microemulsion/corticosteroids/azathioprine , n=92 ) in children who had had liver transplants ( age < or = 16 years , bodyweight < or = 40 kg ) . Initial oral daily doses were 0.30 mg/kg for tacrolimus and 10 mg/kg for ciclosporin microemulsion . Primary endpoint was the incidence of and time to first histologically proven acute rejection .  We excluded patients from analysis if they did not receive the study drug , or were given incorrect medication . Otherwise patients were analysed in accordance with their r and om treatment allocation , irrespective of whether they switched medication during the trial . FINDINGS Median age was 22 months ( IQR 9 - 56 ) in the tacrolimus group and 17 months ( 9 - 54 ) in the ciclosporin microemulsion group . We noted no difference between treatment groups with respect to patient survival ( 93.4 % vs 92.2 % ; p=0.77 ) or graft survival ( 92.3 % vs 85.4 % ; p=0.16 ) at month 12 after transplant . The acute rejection free rate at study end ( Kaplan-Meier method ) was 55.5 % for patients on tacrolimus and 40.2 % for patients on ciclosporin microemulsion ( p=0.0288 ) . The Kaplan-Meier estimate of patients free from corticosteroid-resistant acute rejection at study end was 94.0 % for tacrolimus-treated patients and 70.4 % for ciclosporin-microemulsion-treated patients ( p<0.0001 ) . Overall , incidence of adverse events did not differ between groups . INTERPRETATION Tacrolimus is a safe and effective treatment for the prevention of rejection after liver transplantation in children OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND Calcineurin inhibitors are the most commonly used immunosuppressive drugs in liver transplantation , but the optimum initial immunosuppression regimen is not known . The aim of our study was to compare tacrolimus with microemulsified ciclosporin , in a regimen with st and ardised concomitant immunosuppressive therapy . METHODS In all liver transplant centres in the UK and Republic of Irel and , 606 patients undergoing a first orthotopic liver transplantation were r and omly assigned open-label tacrolimus or microemulsified ciclosporin . Primary outcome was the combined frequency ( whichever occurred first ) of death , retransplantation , or treatment failure for immunological reasons , analysed by intention to treat . FINDINGS 96 % of patients received the treatment allocated to them . The primary outcome was reached in 62 ( 21 % ) of 301 patients in the tacrolimus group versus 99 ( 32 % ) of 305 allocated microemulsified ciclosporin ( relative risk 0.63 [ 95 % CI 0.48 - 0.84 ] , p=0.001 ; time-to-event analysis log-rank test p=0.002 ) : deaths ( 50 [ 17 % ] vs 72 [ 24 % ] ) ; retransplantations ( 11 [ 4 % ] vs 31 [ 10 % ] ) treatment failure for immunological reasons ( 6 [ 2 % ] vs 12 [ 4 % ] ) . The relative risk for the composite outcome was in favour of tacrolimus . The main causes of death in both trial groups were sepsis and multiple organ failure ( 31 [ 10 % ] vs 30 [ 10 % ] ) , and the main cause for retransplantation was hepatic artery thrombosis ( 6 [ 2 % ] vs 17 [ 6 % ] ) . Renal dysfunction and the need for antihypertensive therapy were much the same in both groups . Tacrolimus was more diabetogenic . INTERPRETATION Clinical outcome at 1 year was better with tacrolimus-based immunosuppression than with microemulsified ciclosporin during the first year after liver transplantation . Tacrolimus should be the first choice of calcineurin inhibitor for patients receiving their first liver graft Abstract : Background : This is a 4‐yr follow‐up of a trial using mycophenolate mofetil ( MMF ) induction in orthotopic liver transplantation ( OLT ) . The goal of this study was to evaluate a multidrug approach that would reduce both early and long‐term morbidity related to immunosuppression while maintaining an acceptable freedom from rejection BACKGROUND Immunosuppression in patients with hepatitis C virus ( HCV ) following orthotopic liver transplantation can lead to significant increases in serum viral loads . Our aim was to analyze the effect of a r and omized study of two immunosuppressive agents ( tacrolimus vs. microemulsion cyclosporine ) on the outcome of HCV patients following orthotopic liver transplantation . METHODS From December 1995 to September 1996 , 50 adult patients transplanted for HCV cirrhosis were r and omly assigned to receive  tacrolimus ( Prograf ) ( group 1 , 25 patients ) or microemulsion cyclosporine ( Neoral ) ( group 2 , 24 patients ) . All patients received alpha-interferon after transplantation , and the overall steroid doses were no different between the groups . Serum RNA levels were measured by signal amplification of Chiron . Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens . RESULTS There were more episodes of rejection in the Neoral group , but there were no differences in bacterial and viral infections , nor in the rate of HCV recurrence between the two groups . There were seven deaths in group 1 and eight in group 2 . Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68 % and 67 and 64 % , respectively . CONCLUSIONS ( a ) Both immunosuppression regimens had similar HCV recurrence rates ; ( b ) there were no differences in bacterial or opportunistic infections ; and ( c ) patient and graft survival was similar between the two groups Hepatitis C virus (HCV)-induced cirrhosis is the commonest indication for orthotopic liver transplantation , but HCV recurrence is nearly universal and may worsen patient / graft outcomes . The frequency and severity of HCV recurrence has apparently increased in recent years , raising concern about a possible role for newer immunosuppression regimens in this increase , including potentially tacrolimus . We r and omized 79 patients to receive tacrolimus or cyclosporine as primary immunosuppressant posttransplantation . A pathologist blinded to treatment review ed serial liver biopsies . Month 12 cumulative probabilities of histological hepatitis C recurrence for tacrolimus- and cyclosporine-treated patients were .38 and .54 ( P = .19 ) and failure / death were .25 and .28 , respectively ( P = .789 ) . Although cyclosporine-treated patients had significantly larger increases in median serum HCV RNA levels ( months 1 , 6 , and 12 ) , no significant differences were observed between the two treatment arms in histologically-diagnosed HCV recurrence / survival rates . In conclusion , choice of calcineurin inhibitors does not impact severity of recurrent HCV BACKGROUND Many reports of successful early withdrawal of regular maintenance steroids in transplant recipients have appeared in recent years . The question now arises whether , in the current age of powerful nonsteroidal immunosuppressants such as Neoral and Tacrolimus , routine administration of steroids posttransplant is necessary at all . This single center pilot study reports on the feasibility , safety , and efficacy of single agent immunosuppression " ab initio " with either Neoral or Tacrolimus , and no routine or maintenance steroids . METHODS A total of 64 adult patients receiving first liver grafts for a variety of indications were r and omized to receive either Neoral 5 mg/kg BDS or Tacrolimus 0.05 mg/kg BDS orally . Liver biopsies were performed on postoperative days 5 and 10 , and whenever else clinical ly indicated . Rejection episodes were treated with 1.0 g of Methylprednisolone daily for 3 consecutive days . A further episode of rejection after two courses 
    Output:
    
Tacrolimus is superior to cyclosporin in improving survival ( patient and graft ) and preventing acute rejection after liver transplantation , but it increases the risk of post-transplant diabetes .