Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir.

BACKGROUND & AIMS: New interferon-free anti-HCV regimens are highly efficacious with a favorable safety profile. We assessed health-related quality of life (HRQL) and work productivity in patients with different stages of hepatic fibrosis treated with sofosbuvir+ledipasvir. METHODS: Four questionnaires [Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index:Specific Health Problem (WPAI:SHP)] were administered at baseline, during, and after treatment with sofosbuvir+ledipasvir+ribavirin or sofosbuvir+ledipasvir (ION-1,2,3 clinical trials). Metavir fibrosis stage was determined from pre-treatment liver biopsies. RESULTS: There were 1005 patients included (stage F0: n=94; F1: n=311; F2: n=301; F3: n=197; F4: n=102). At baseline, patients with more advanced fibrosis had more HRQL impairments, predominantly related to physical functioning (stage 0 vs. stage 4 by up to 0.126 on a normalized 0-1 scale p<0.0001). During and post-treatment, HRQL remained lower in patients with advanced fibrosis. After achieving sustained virologic response, significant improvements from baseline in most HRQL domains were observed regardless of fibrosis stage (by 0.024-0.103 on a 0-1 scale; all p>0.05 across fibrosis stages). In multivariate analysis, advanced fibrosis was independently associated with impairment of HRQL and work productivity (beta up to -0.056 in comparison with none-to-mild fibrosis, p<0.05). However, improvement of HRQL and work productivity after viral clearance was not related to the stage of fibrosis (all p>0.05). CONCLUSIONS: Although advanced hepatic fibrosis is associated with HRQL and work productivity impairment, viral eradication with sofosbuvir+ledipasvir leads to HRQL improvement regardless of fibrosis stage. HCV patients with early fibrosis experience similar improvement of patient reported outcomes as those with advanced fibrosis.

Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: Results from the ION-1, -2, and -3 clinical trials.

UNLABELLED: Treatment with interferon (IFN) and ribavirin (RBV) significantly impairs quality of life and other patient-reported outcomes (PROs). Patient experience with IFN- and RBV-free anti-HCV (hepatitis C virus) regimens has not been reported. We assessed PROs in patients treated with ledipasvir and sofosbuvir (LDV/SOF) with and without RBV. Four different PRO questionnaires were administered at baseline, during, and post-treatment in HCV genotype 1 patients treated with LDV/SOF±RBV (ION-1, -2, and -3). A total of 1,952 patients were enrolled to be treated for 8 (N = 431), 12 (N = 867), or 24 weeks (N = 654) with LDV/SOF (N = 1,080) or LDV/SOF+RBV (N = 872). Baseline demographics and psychiatric disorders were similar between treatment groups (all P > 0.05). Patients receiving LDV/SOF regimens showed significant improvement of PRO scores during treatment (up to +7.4%, +7.0%, and +6.7% on a normalized 0%-100% scale in the 8-, 12-, and 24-week-long treatment groups, respectively (all P < 0.0001). These PRO improvements coincided with early viral suppression after 2 weeks of treatment and maximized by the end of treatment. On the other hand, during treatment with LDV/SOF+RBV, PRO scores declined (up to -5.5% regardless of treatment duration; P < 0.0001). Receiving RBV was an independent predictor of PRO impairment in multivariate analysis (beta up to -5.9%; P < 0.0001). Patients who achieved sustained virological response at 12 weeks showed significant improvement of their PROs post-treatment (up to +8.3%; P < 0.0001). CONCLUSION: IFN- and RBV-free regimens with LDV/SOF result in early HCV suppression with simultaneous improvement in PROs that continued throughout the duration of treatment and post-treatment.

Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients Coinfected With Hepatitis C Virus and HIV: The Impact on Patient-Reported Outcomes.

BACKGROUND: Sofosbuvir-containing regimens have been approved for treatment of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients. We assessed the effect of treatment with sofosbuvir and ribavirin on patient-reported outcomes (PROs) in individuals with HIV/HCV coinfection. METHODS: HIV/HCV-coinfected patients were treated for 12 or 24 weeks with sofosbuvir and ribavirin. Matched HCV-monoinfected controls were also evaluated. All subjects completed standard PRO questionnaires before, during, and after treatment. RESULTS: Included were 497 participants from the PHOTON-1 and PHOTON-2 clinical trials. At baseline, more impairment in PRO scores was noted in HIV/HCV-coinfected patients, compared with HCV-monoinfected patients. During treatment, moderate decrements in PRO scores (change, up to -6.8% on a 0%-100% scale; P = .0053) were experienced regardless of treatment duration and were similar to those for HCV-monoinfected patients (all P > .05). In 413 HIV/HCV-coinfected patients with a virologic response sustained for 12 weeks after treatment cessation, most PRO scores improved (change, up to +7.6%; P < .0001), similar to findings for HCV-monoinfected patients. In multivariate analysis, in addition to clinico-demographic predictors, coinfection with HIV was associated with PRO impairment at baseline (beta, up to -7.6%; P < .002) but not with treatment-emergent changes in PRO scores (all P > .05). CONCLUSIONS: Patients with HIV/HCV coinfection tolerate interferon-free sofosbuvir-based anti-HCV regimens well and, despite the presence of some baseline impairment, have treatment-emergent changes in PRO scores that are similar to those of patients with HCV monoinfection. CLINICAL TRIALS REGISTRATION: NCT01667731 (PHOTON-1), NCT01783678 (PHOTON-2), NCT01604850 (FUSION), and NCT01682720 (VALENCE).

Anti-adipocyte antibody response in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: A significant number of autoantibodies have been reported in patients with non-alcoholic fatty liver disease (NAFLD) patients. In the present study, our aim was to assess the role of disease and cell-specific antibodies, namely anti-adipocyte antibodies (anti-AdAb) in patients with NAFLD and non-alcoholic steatohepatitis (NASH). METHODS: Flow cytometry was used to detect the presence of anti-AdAb (immunoglobulin M [IgM] and immunoglobulin G [IgG]) in sera from patients with biopsy-proven NAFLD (n = 98) and in controls (n = 49) without liver disease. Univariate and multivariate analysis was performed to draw associations between anti-AdAb IgM and IgG levels and the different clinical variables. RESULTS: Patients with NAFLD had significantly higher levels of anti-AdAb IgM and significantly lower levels of AdAb IgG when compared with controls (P = 0.002 and P < 0.001, respectively). Patients with NASH had significantly higher levels of anti-AdAb IgM when compared with non-NASH NAFLD patients, P = 0.04. In multivariate analysis, anti-AdAb IgM was independently associated with a higher risk for NASH (odds ratio[OR]: 2.90 [confidence interval (CI) 1.18-7.16], P = 0.02). Anti-AdAb IgM was also found to be independently associated with portal inflammation in patients with NAFLD (OR: 3.01 [CI 1.15-7.90 P = 0.02]). CONCLUSIONS: Anti-AdAb IgM was independently associated with NAFLD and NASH while anti-AdAb IgG was found to be protective against NAFLD. Anti-AdAb IgM was found specifically to be associated with the inflammatory processes in NAFLD. These findings indicate that the anti-AdAb IgM and IgG may play an immunomodulatory role in the pathogenesis of NAFLD and NASH.

Patient-reported outcomes in chronic hepatitis C patients with cirrhosis treated with sofosbuvir-containing regimens.

UNLABELLED: Whether the presence of cirrhosis influences patient-reported outcomes (PROs), including health-related quality of life, during treatment with newly available anti-HCV (hepatitis C virus) regimens is unclear. Our aim was to assess the association of cirrhosis with PROs in patients treated with sofosbuvir (SOF)-containing regimens. Four PRO questionnaires (Short Form-36 [SF-36], Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F], Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), and the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI-SHP]) were administered to subjects receiving SOF and ribavirin (RBV; FUSION trial, N=201, 34% cirrhosis; VALENCE trial: N=333, 21% cirrhosis) and SOF, RBV, and pegylated interferon (Peg-IFN; NEUTRINO trial: N=327, 17% cirrhosis). HCV patients with cirrhosis showed significant impairment of PROs before initiation of treatment. During treatment, patients with cirrhosis treated with the IFN-free regimen experienced moderate decline in their PRO scores (0.6%-5.2% on a normalized scale of the summary scores; all P>0.02). In contrast, patients with cirrhosis treated with IFN-containing regimen showed decline in PRO scores that ranged from 3.4% to 16.0% (all P<0.005). Nevertheless, by follow-up week 12, no PRO decrement from baseline was observed in patients with cirrhosis regardless of the treatment regimen. Furthermore, in patients with cirrhosis with HCV who achieved sustained virological response at 12 weeks (SVR-12), some improvement in PROs from baseline was observed. During treatment, changes in PRO scores were similar between patients with and without cirrhosis for both treatment regimens (all P>0.05). Independent predictors of lower PROs in patients with cirrhosis included baseline depression, anxiety, fatigue, high HCV viral load, female gender, and receiving IFN-containing treatment. CONCLUSIONS: Treatment with SOF+RBV with or without Peg-IFN is tolerated by HCV patients with and without cirrhosis in terms of their PRO scores. After achieving SVR-12 with the IFN-free regimen, patients with cirrhosis showed improvement in some aspects of their PROs.

Patient-reported outcomes assessment in chronic hepatitis C treated with sofosbuvir and ribavirin: the VALENCE study.

BACKGROUND & AIM: Interferon (IFN) negatively impacts patients' well-being and patient-reported outcomes (PROs). Our aim was to assess PROs during treatment with an IFN-free regimen [sofosbuvir (SOF)+ribavirin (RBV)]. METHODS: Four PRO questionnaires [Short Form-36 (SF-36), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index: Specific Health Problem (WPAI:SHP)] were administered at baseline, end-of-treatment and post-treatment to 334 HCV genotype 2 and 3 patients (naïve or treatment-experienced) enrolled in the VALENCE study. Of these, 250 genotype 3 patients were treated for 24 weeks while 73 genotype 2 and 11 genotype 3 patients received 12 weeks of treatment. RESULTS: Baseline PRO scores were similar between the two arms of the study. Throughout and after treatment, patients receiving 12 or 24 weeks had similar FACIT-F, CLDQ-HCV, SF-36 and WPAI:SHP scores (all p>0.05). Compared to their own baseline scores, patients receiving SOF+RBV experienced modest declines in some aspects of SF-36, CLDQ-HCV, fatigue and WPAI:SHP scores (p = 0.04 to <0.0001). By follow-up week 12, all PRO scores returned to the pre-treatment levels (p>0.05). In patients achieving SVR-12 (regardless of the regimen), significant improvements were noted in general health (p = 0.0004), CLDQ-HCV (p<0.0001), fatigue (p = 0.005), emotional well-being (p<0.0001) and physical component summary score of SF-36 (p = 0.0022). In multivariate analysis, baseline depression, fatigue, insomnia, cirrhosis, and treatment-related adverse events were the most consistent predictors of PRO impairment (all p<0.05). CONCLUSIONS: PROs are minimally impacted by SOF+RBV regimens. An additional 12 weeks of treatment does not substantially add to the PRO burden.

Health-related quality of life following isolated aortic valve surgery: is earlier intervention better?

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the health-related quality of life (HRQL) in conjunction with clinical outcomes following aortic valve replacement (AVR) surgery. In these times of healthcare change, quality measures of the success of a procedure go beyond clinical outcomes, with patient reports of HRQL considered important. METHODS: All patients who had undergone AVR surgery were followed prospectively through the authors' valve registry and the local Society of Thoracic Surgery (STS) database. The HRQL (Short-Form 12 and Minnesota Living with Heart Failure Questionnaire) was collected preoperatively, and at six and 12 months after surgery. RESULTS: Since 2005, a total of 459 patients have undergone isolated AVR surgery. The mean age, ejection fraction and STS risk score were 65.8 +/- 13.6 years, 57.7 +/- 11.0%, and 2.8 +/- 3.5 (range: 0.4-47.9), respectively. The median (IQR) length of hospital stay was 5 (3-7) days. Compared to the STS national norms, all clinical outcomes were excellent. A Kaplan-Meier analysis showed the two year cumulative survival as 92.0%. After 12 months the physical and mental HRQL had improved significantly, surpassing age and heart disease norms (p < 0.001 and p = 0.02, respectively). Multivariate analysis determined that a higher 12-month physical HRQL was predicted by a lower STS risk score (B = -1.3, p < 0.001) and a lower perioperative morbidity (B = -5.5, p = 0.02) after adjustment for baseline HRQL, age, and gender. In a subset of patients classified as 'symptomatic', as determined by higher MLHF scores, the HRQL scores were increased to age norms and surpassed the heart disease norms. CONCLUSION: Patients who undergo AVR can expect excellent clinical and HRQL outcomes, with greater benefits the earlier the surgery is carried out. The tracking of HRQL is valuable in understanding the success of a procedure from the patients' perspective.

Health-related quality of life after coronary artery bypass grafting surgery and the role of gender.

OBJECTIVE: Heart disease is the leading cause of death for women. Previous studies suggest that women undergoing coronary artery bypass (CABG) surgery present with a higher severity of disease and that this may be an indicator of delays in treatment preceding diagnosis thus presenting challenges for recovery. The aim of this study was to examine gender differences in CABG morbidity and reported health-related quality of life (HRQL) at baseline and six months post-surgery. It was hypothesized that female gender would be an independent predictor for lower HRQL at six months following CABG surgery. METHODS: Four hundred and ninety-six (n=496) adult patients who underwent a first-time, isolated CABG procedure with baseline and 6-month follow-up were included. Stepwise multivariate regressions were conducted to evaluate the factors predictive of 6-month HRQL scores. RESULTS: Females had more preoperative co-morbidities and scored significantly lower on HRQL compared to males at both baseline (p values<0.01) and six months (p values<0.01) on all ten domains. Gender was a significant predictor of 6-month HRQL in regression models for 8 out of 10 HRQL domains including Physical Component Summary score (B=-2.54, p=0.02). CONCLUSIONS: Female patients were at higher risk as reflected by their perioperative risk factors and baseline HRQL. These findings may reflect a delayed referral for surgery. Results indicated that female gender predicts lower HRQL 6-months post-CABG surgery, which can have an impact on recovery and outcomes. Efforts should be made to identify and treat female patients earlier to improve post-surgical outcomes.

The impact of surgical ablation for atrial fibrillation in high-risk patients.

BACKGROUND: Data reported by The Society of Thoracic Surgeons adult cardiac surgery database demonstrate that only 38% of patients with atrial fibrillation (AF) underwent a concomitant surgical ablation. Surgeons are reluctant to add complexity and potential morbidity by including an additional procedure when performing surgery in higher operative risk patients. We investigated perioperative and long-term outcomes in high-risk patients who underwent open heart surgery with or without surgical ablation for AF. METHODS: An additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) higher than 6 defined high-risk patients. Perioperative outcomes were captured prospectively, and long-term survival and quality of life were assessed. Propensity score matching using a 0.25 caliper was conducted between the surgical ablation group and the nonablation group (no history of AF). RESULTS: The propensity score matching analysis included 178 patients per group. The groups were similar on preoperative characteristics including age, ejection fraction, EuroSCORE, and surgical procedures. The perioperative outcomes were similar between groups, including length of stay, permanent stroke, renal failure, 30-day readmissions, and operative (<30 days) mortality. Cumulative survival over 5 years also did not differ between groups (74.4% versus 69.7%, p=0.34). CONCLUSIONS: The addition of an AF surgical ablation procedure did not add operative risk to patients considered high risk, and potentially improved long-term outcome for the subgroup of patients who had their AF ablated. This study suggests that the degree of surgical risk should not be the only decision factor when evaluating this challenging group of patients for surgical ablation.

Evaluation of patient safety culture: a survey of clinicians in a cardiovascular operating room.

OBJECTIVE: The aim of this study was to understand the perceived safety culture and attitudes of caregivers in a large cardiovascular operating room (CVOR) in a mid-Atlantic state where more than 1500 procedures are performed annually to include ventricular assist device placement and heart and lung transplantations. METHODS: We analyzed deidentified data obtained from a safety survey completed anonymously by frontline caregivers in the CVOR via the Safety Attitudes Questionnaire developed by Pasquel Metrics. RESULTS: The responses from the CVOR clinicians were overall positive for their perceptions of the CVOR safety climate, with the majority saying they would feel safe being treated as a patient, liked their job, and were aware of the proper channels regarding patient safety. However, many made claims of experiencing fatigue and stress due to an excessive workload and participation in emergency situations. Furthermore, the support/clinical perfusion teams were found to have experienced the greatest amount of stress and discomfort, whereas it seems the surgeons were impacted the least. CONCLUSIONS: This study suggests that reactions to different situations in the operating room are dependent on the role of the caregiver. Therefore, interventions to improve communication among the caregivers must be geared on an individual group basis.

Strict versus liberal target range for perioperative glucose in patients undergoing coronary artery bypass grafting: a prospective randomized controlled trial.

OBJECTIVE: The purpose of this study was to test the hypothesis that a liberal blood glucose strategy (121-180 mg/dL) is not inferior to a strict blood glucose strategy (90-120 mg/dL) for outcomes in patients after first-time isolated coronary artery bypass grafting and is superior for glucose control and target blood glucose management. METHODS: A total of 189 patients undergoing coronary artery bypass grafting were investigated in this prospective randomized study to compare 2 glucose control strategies on patient perioperative outcomes. Three methods of analyses (intention to treat, completer, and per protocol) were conducted. Observed power was robust (>80%) for significant results. RESULTS: The groups were similar on preoperative hemoglobin A(1c) and number of diabetic patients. The liberal group was found to be noninferior to the strict group for perioperative complications and superior on glucose control and target range management. The liberal group had significantly fewer patients with hypoglycemic events (<60 mg/dL; P < .001), but severe hypoglycemic events (<40 mg/dL) were rare and no group differences were found (P = .23). These results were found with all 3 methods of analysis except for blood glucose variability, maximum blood glucose, and perioperative atrial fibrillation. CONCLUSIONS: This study demonstrated that maintenance of blood glucose in a liberal range after coronary artery bypass grafting led to similar outcomes compared with a strict target range and was superior in glucose control and target range management. On the basis of the results of this study, a target blood glucose range of 121 to 180 mg/dL is recommended for patients after coronary artery bypass grafting as advocated by the Society of Thoracic Surgeons.

Performance of four risk algorithms in predicting intermediate survival in patients undergoing aortic valve replacement.

OBJECTIVE: : Several risk models exist to predict operative outcomes after cardiac surgery and are used in selecting patients for alternative procedures such as transcatheter valve implantation. We sought to evaluate the performance of the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) model in accurately identifying patients at high risk for aortic valve replacement (AVR). METHODS: : Three hundred and ninety four consecutive patients who underwent isolated AVR from January 1, 2001, to July 1, 2007, at a tertiary care center were analyzed using the STS database. Patients were stratified into tertiles according to operative surgical risk calculated by the four models [STS-PROM, European system for cardiac operative risk evaluation (EuroSCORE), Ambler, and Providence]. Vital status at 1 year was determined using the National Death Index and Social Security Death Index. RESULTS: : There were 310 low-risk patients, 56 intermediate-risk patients, and 28 high-risk patients with respect to the STS-PROM. The predicted risk of death for the low-risk, intermediate-risk, and high-risk groups were 2.4% ± 1.1%, 6.9% ± 1.4%, 15.8% ± 7.6% (P < 0.001) with respect to the STS-PROM model. Actual operative mortality for each respective group was 1.94%, 5.36%, 14.29% (P < 0.001) and 1-year mortality was 3.23%, 12.50%, 21.43% (P < 0.001), respectively. CONCLUSIONS: : High-risk patients have significantly high mortality after AVR. The STS-PROM accurately predicts operative mortality and can be used to predict 1-year survival as well. This risk model may be preferentially used instead of the EuroSCORE.

The effect of previous coronary artery stenting on short- and intermediate-term outcome after surgical revascularization in patients with diabetes mellitus.

OBJECTIVES: Percutaneous intervention for coronary revascularization is associated with an increased risk of repeat revascularization, especially in patients with diabetes mellitus. In this study we sought to examine the effect of previous percutaneous intervention on the rate of adverse perioperative outcome and intermediate-term survival in patients undergoing coronary artery bypass surgery. METHODS: Between January 1, 2001, and December 31, 2006, 1758 consecutive patients with diabetes mellitus who underwent first-time isolated coronary artery bypass surgery were identified. Survival and major perioperative complications for 1537 patients who did not have prior percutaneous intervention (group 1) were compared with those in 221 patients with prior percutaneous intervention (group 2) after adjusting for baseline risk factors. Vital status was determined by using the National Death Index and Social Security Death Index. Age-adjusted survival at 2 years' follow-up was calculated with the Cox singular proportional hazards model. RESULTS: At baseline, group 2 patients had higher incidences of hypercholesterolemia and myocardial infarction. Compared with group 1 patient, group 2 patients had significantly higher operative mortality (adjusted odds ratio, 4.05; 95% confidence interval, 1.41-11.63), perioperative major adverse cardiac events (adjusted odds ratio, 2.72; 95% confidence interval, 1.08-6.85), and atrial fibrillation (adjusted odds ratio, 1.97; 95% confidence interval, 1.29-3.01). Group 2 patients had worse age-adjusted survival at 2 years' follow-up (93.4% vs 87.4%, P < .017). CONCLUSIONS: Patients with diabetes mellitus and a history of percutaneous coronary stenting before coronary artery bypass surgery were found to have an increased risk of operative death, increased perioperative complications, and decreased age-adjusted survival at 2 years' follow-up.

Survival and quality of life following elective open-heart surgery.

Eight hundred thirty-six patients who had open-heart surgery were available for analysis of health-related quality of life (HRQL) data and survival at the 1-year follow-up. Elective open-heart surgery patients with decreasing HRQL at 1 year following surgery may experience a survival disadvantage in comparison with those patients experiencing positive gains. Clinical care should extend beyond the immediate postoperative period.

The association between early outcome, health-related quality of life, and survival following elective open-heart surgery.

We investigated the impact of perioperative complications on patients' health-related quality of life (HRQL) and intermediate-term survival after cardiac surgery. Improved results for cardiac surgery are well demonstrated in low rates of operative mortality and morbidity. However, the association between perioperative morbid events, HRQL at 1 year, and survival is unclear. We performed a prospective study among 836 elective cardiac surgery patients to assess the impact of perioperative outcomes on survival and HRQL at 1 year. Health-related quality of life was generated using the 20-item short-form questionnaire. Kaplan-Meier and life-table estimates were used to examine the relationship of HRQL at 1-year and intermediate-term survival. All HRQL domains were statistically improved at 1 year, with the highest gains in general health perception (+19.4%) and the least gains in social (+5.1%) and mental (+5.1%) domains. Patients experiencing 1 or more perioperative complication or increased length of stay reported similar HRQL scores as patients with no complications. Patients with negative changes in social (94.5% vs 99.2%, P < .001) and general health perception (99.4% vs 95.5%, P < .001) domains showed a reduced survival compared with patients with positive HRQL gains at 2 to 5 years after surgery. Perioperative complications had minimal or no effect on HRQL at 1 year after cardiac surgery.

Two-dose daclizumab induction therapy in 209 liver transplants: a single-center analysis.

BACKGROUND: Patient and graft survival after liver transplantation are adversely affected by early posttransplant renal dysfunction. Therefore, our immunosuppressive strategies should be as "renal sparing" as possible. This is the largest published series to date using daclizumab induction therapy in a renal-sparing regimen. METHODS: This is a retrospective, nonrandomized study comparing 209 adult liver transplants with daclizumab induction to 115 transplants with no induction. RESULTS: Patient and graft survival were similar, despite higher pretransplant acuity of illness and older age in the induction group. Acute rejection within the first 6 months occurred less commonly in the induction group (25.4% vs. 39.1%, P=0.01), despite significantly delayed initiation and lower doses of a calcineurin inhibitor. Mycophenolate mofetil was used more commonly in induction patients, but the efficacy of daclizumab in preventing rejection was independent of this. Patients with a pretransplant creatinine concentration 1.5 mg/dL or less had less rejection if they received induction. Renal function worsened in noninduction patients but showed sustained improvement throughout follow-up in induction patients with a pretransplant creatinine concentration greater than 1.5 mg/dL. Induction therapy provided better rejection prophylaxis among those requiring temporary calcineurin inhibitor cessation because of renal dysfunction. The incidences of histologic hepatitis C recurrence and cytomegalovirus infection were similar in each group. CONCLUSIONS: Liver recipients with and without pretransplant renal dysfunction have less acute rejection with daclizumab induction therapy. This is not associated with an increased risk of over-immunosuppression. Sustained renal improvement in recipients with pretransplant renal dysfunction is possible with daclizumab induction.

"High-risk" renal transplantation: evolving definitions at a single center.

Characterization of renal transplant recipients as "high-risk" originated in the 1970's, although attributes that defined this category, such as diabetes mellitus, are no longer applicable. The changing paradigm of risk after renal transplantation reflects the impact of nonspecific advances in clinical care, specific interventions that address previously defined problems, changing demographics, and new issues that have arisen as a consequence of changes in clinical practice. In the current era, diabetes, retransplantation, and presensitization are no longer considered risk factors for poor outcomes after kidney transplantation. Significant risk factors influencing intermediate-term graft survival now include donor and recipient age over 60 years, DR mismatching (only in kidneys from deceased donors), time awaiting transplantation, and African-American race. Current clinical approaches to care of the renal transplant candidate/recipient focus on minimizing the impact of identified risk factors rather than avoiding transplantation altogether. For most ESRD patients, the greatest risk lies in not receiving a transplant.