***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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    ***EXAMPLES*** 
    Input: Efficacy and safety of protein kinase C inhibitor sotrastaurin ( STN ) with tacrolimus ( TAC ) was assessed in a 24‐month , multicenter , phase II study in de novo liver transplant recipients . A total of 204 patients were r and omized ( 1:1:1:1 ) to STN 200 mg b.i.d . + st and ard‐exposure TAC ( n = 50 ) or reduced‐exposure TAC ( n = 52 ) , STN 300 mg b.i.d . + reduced‐exposure TAC ( n = 50 ) , or mycophenolate mofetil ( MMF ) 1 g b.i.d . + st and ard‐exposure TAC ( control , n = 52 ) ; all with steroids .  Owing to premature study termination , treatment comparisons were only conducted for Month 6 . At Month 6 , composite efficacy failure rates ( treated biopsy‐proven acute rejection episodes of Banff grade ≥1 , graft loss , or death ) were 25.0 % , 16.5 % , 20.9 % and 15.9 % for STN 200 mg + st and ard TAC , STN 200 mg + reduced TAC , STN 300 mg + reduced TAC and control groups , respectively . Median estimated glomerular filtration rates were 84.0 , 83.3 , 81.1 and 75.3 mL/min/1.73 m2 , respectively . Gastrointestinal events ( constipation , diarrhea , and nausea ) , infection , and tachycardia were more frequent in STN groups . More patients in STN groups experienced serious adverse events compared with the control group ( 62.3–70.8 % vs. 51.9 % ) . STN‐based regimens were associated with a higher efficacy failure rate and higher incidence of adverse events with no significant difference in renal function between the groups BACKGROUND Tacrolimus ( Tac ) and mycophenolate mofetil ( MMF ) are newly approved immunosuppressive agents . However , the safety and efficacy of the combination of MMF and Tac in primary liver transplantation has not been determined . METHODS An Institutional Review Board-approved , open-label prospect i ve r and omized protocol was initiated to study the efficacy and toxicity of Tac and steroids ( double-drug therapy ) versus Tac , steroids , and MMF ( triple-drug therapy ) in primary adult liver transplant recipients . Both groups of patients began on the same doses of Tac and steroids .  Patients r and omized to triple-drug therapy also received 1 g of MMF twice a day . RESULTS Between August 1995 and January 1997 , 200 patients were enrolled , 99 in double-drug therapy and 101 in triple-drug therapy . All patients were followed until May 1997 , with a mean follow-up of 12.7 months . During the study period , 28 of 99 patients in double-drug therapy received  MMF  to control ongoing acute rejection , nephrotoxicity , and /or neurotoxicity . On the other h and , 61 patients in triple-drug therapy discontinued MMF for infection , myelosuppression , and /or gastrointestinal disturbances . By an " intention-to-treat analysis , " the actuarial 1-year patient survival rate was 85.1 % in double-drug therapy and 83.1 % in triple-drug therapy ( P=0.77 ) . The actuarial 1-year graft survival rate was 80.2 % for double-drug therapy and 79.2 % for triple-drug therapy ( P=0.77 ) . Forty-one patients ( 41.4 % ) in double-drug therapy and 32 ( 31.7 % ) in triple-drug therapy had at least one episode of rejection , but this was not statistically significant ( P=0.15 ) . The mean maintenance dose of corticosteroids was slightly lower in triple-drug compared with double-drug therapy . CONCLUSION Patient and graft survival rates were similar in both groups . There was a trend to a lower incidence of rejection , reduced nephrotoxicity , and a lesser amount of maintenance corticosteroids in triple-drug therapy compared with double-drug therapy Although steroid withdrawal has been successfully performed in heart and kidney transplant recipients , no controlled studies of SW have been carried out in liver transplant patients . To evaluate this possibility a prospect i ve controlled study was carried out in 46 liver transplant recipients operated on after may 1991 . They all received a sequential quadruple immunosuppression consisting of 3 mg/kg antithymocyte globulins ( RATG ) for the first 5 postoperative days , cyclosporin A ( starting from day 3 - 5 and maintaining parenteral whole-blood trough levels at 200 - 300 ng/ml during the first month and at 150 - 250 thereafter ) , azathioprine ( 1 mg/kg per day for the first month ) and steroids . Prednisone was started at a dose of 200 mg per day 1 and then tapered to 20 mg/day over the first posteroperative week ; this dose was maintained until day 90 when the patients were r and omly allocated either to long-term steroid therapy ( 0.1 mg/kg per day ) or to steroid withdrawal . Minimum follow-up after r and omization was 6 months ( 6 - 27 months ) . Liver biochemistry was checked at regular intervals throughout the follow-up period . Liver biopsies were performed whenever clinical ly indicated and also in the first 19 patients during readmission for annual review . The incidence ot acute and chronic rejection 90 days from liver transplantation was 2.5 % in patients maintained on long-term therapy . No patient in the steroid-withdrawal group had experienced either an acute or a chronic rejection episode so far . Steroid-related complications did not differ significantly between the two groups . The most recent interim analysis showed that steroid withdrawal is a safe undertaking in liver transplant recipients and may be successfully accomplished in almost all patients We studied the outcome of 345 liver transplant patients who received tacrolimus‐based immunosuppressive therapy either as a dual regimen ( with corticosteroids  , n=172 ) or as a triple regimen ( with corticosteroids and azathioprine , n=173 ) for 3 months after transplantation ( 3‐month cohort ) . A further analysis was conducted for the first 195 patients r and omised ( dual n=100 , triple n=95 ) who were followed up for 12 months after transplantation ( 12‐month cohort ) . For the 3‐month cohort , patient survival was 90.7 % ( dual ) and 91.9 % ( triple ) , graft survival after 3 months was 88.4 % ( dual therapy ) and 89.6 % ( triple therapy ) . Acute rejections were experienced by 67/172 , 39.0 % of patients on dual therapy and by 60/173 , 34.7 % of patients on triple therapy ; corticosteroid‐resistant rejections were reported in 9 patients ( 5.2 % ) in either treatment group . The overall safety profile was similar for the two treatment groups . Significant differences , however , were found for thrombocytopenia ( dual 13/172 , 7.6 % , triple 37/173 , 21.4 % , p<0.001 ) and leukopenia ( dual 4/172 , 2.3 % , triple 24/173 , 13.9 % , p<0.001 ) . For the 12‐month cohort , patient survival was 85.6 % ( dual ) and 88.4 % ( triple ) after 1 year . Graft survival was 81.7 % ( dual ) and 85.2 % ( triple ) 12 months after transplantation . Acute rejections were reported for 38/100 , 38.0 % of patients on dual therapy and 36/95 , 37.9 % of patients on triple therapy , corticosteroid‐resistant rejections were 7/100 , 7.0 % ( dual ) and 7/95 , 7.4 % ( triple ) of patients . In the 12‐month cohort , no significant differences in the safety profiles of the treatment groups were found . We conclude that both tacrolimus‐based dual and triple drug regimens  provide effective and safe immunosuppression following orthotopic liver transplantation This r and omized , prospect i ve , multicenter trial compared the safety and efficacy of steroid-free immunosuppression ( IS ) to the safety and efficacy of 2 st and ard IS regimens in patients undergoing transplantation for hepatitis C virus ( HCV ) infection . The outcome measures were acute cellular rejection ( ACR ) , severe HCV recurrence , and survival .  The patients were r and omized ( 1:1:2 ) to tacrolimus ( TAC ) and corticosteroids ( arm 1 ; n = 77 ) , mycophenolate mofetil ( MMF ) , TAC , and corticosteroids ( arm 2 ; n = 72 ) , or  MMF , TAC , and daclizumab induction with no corticosteroids  ( arm 3 ; n = 146 ) . In all , 295 HCV RNA-positive subjects were enrolled . At 2 years , there were no differences in ACR , HCV recurrence ( biochemical evidence ) , patient survival , or graft survival rates . The side effects of IS did not differ , although there was a trend toward less diabetes in the steroid-free group . Liver biopsy sample s revealed no significant differences in the proportions of patients in arms 1 , 2 , and 3 with advanced HCV recurrence ( ie , an inflammation grade ≥ 3 and /or a fibrosis stage ≥ 2 ) in years 1 ( 48.2 % , 50.4 % , and 43.0 % , respectively ) and 2 ( 69.5 % , 75.9 % , and 68.1 % , respectively ) . Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV , steroid sparing has no clear advantage in comparison with traditional IS Background . Calcineurin inhibitors ( CNIs ) play the key role in immunosuppressive protocol s yet are often associated with numerous side effects . Renal insufficiency , hypertension , hyperglycemia , and increased risk of secondary malignancy are major problems in short- and long-term follow-up of liver transplant patients .  Mycophenolate mofetil ( MMF ) has proved to be a potent immunosuppressive agent free of the CNI-associated side effects . Patients and Methods . One hundred fifty patients who received liver transplantation at our institution ( 1998–2003 ) were prospect ively r and omized : 75 patients continued CNI st and ard therapy , 75 patients were switched to MMF monotherapy , and follow-up was 5 years . Incidence of rejection , renal complication , cardiovascular , neurological and gastrointestinal adverse effects , and diabetes and malignancy development was recorded . Graft biopsies were performed every 2 to 3 years . Results . No significant difference regarding the incidence of acute rejection was detected . A trend to higher rejection frequency was apparent in the MMF monotherapy group . Chronic rejection was absent ; organ and patient survival were identical in the two groups . No significant difference occurred concerning the incidence of cardiovascular , gastrointestinal or neurological adverse effects , or the development of malignancies . Renal function improved significantly in patients with renal insufficiency when patients treated with CNI were switched to MMF monotherapy . Conclusion . MMF monotherapy may serve as safe long-term immunosuppression after liver transplantation for a subgroup of patients . Especially for patients with renal insufficiency  MMF offers immunosuppression without the risk of nephrotoxicity Hepatitis C is the most common indication for liver transplantation ( LT ) in the United States . Recurrence of hepatitis C virus ( HCV ) infection post-LT remains a problem for which there is no completely satisfactory treatment . The aim of the present study is to evaluate mycophenolate mofetil ( MMF ) , which has both immunosuppressive and antiviral properties , to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival .  Between August 1995 and May 1998 , a total of 106 patients who were HCV positive before LT were r and omized to tacrolimus ( TAC ) and prednisone versus TAC , prednisone , and MMF therapy . The rate of recurrence of HCV , patient and graft survival , incidences of rejection , and histological findings were examined . Fifty six patients were r and omized to TAC and steroid therapy ( double [ D ] drug ; group D ) , and 50 patients were r and omized to TAC , steroid , and MMF therapy ( triple [ T ] drug ; group T ) . Liver biopsies were performed when liver function was abnormal ; protocol liver biopsies were not performed . Mean follow-up was 4.3 + /- 0.8 years . Actuarial patient survivals at 4 years were 72.6 % in group D and 73.8 % in group T ( P = not significant ) . Actuarial graft survivals at 4 years were 65.6 % in group D and 65. 
    Output:
    
Based on very low- quality evidence from network meta- analysis , we found no evidence of difference between different immunosuppressive regimens .
We found very low- quality evidence from network meta- analysis and low- quality evidence from direct comparison that cyclosporine A causes more retransplantation compared with tacrolimus .