Dilip Moonka

Henry Ford Hospital, Detroit, Michigan, United States

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Publications (59)238.78 Total impact

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    ABSTRACT: Sirolimus (SRL) is an immunosuppressant often used in liver transplantation (LT) to mitigate renal insufficiency associated with calcineurin inhibitors. Sirolimus can cause hyperlipidemia, but its association with coronary artery disease (CAD) and cerebrovascular accidents (CVAs) is unclear. The purpose of this study was to assess the risk of CAD and CVAs with the use of SRL in LT recipients. We retrospectively reviewed all of our LT recipients from 2000 to 2011. Patients with multiorgan transplant, multiple liver transplants, everolimus therapy, or survival <3 months were excluded. The 803 remaining patients were divided into 3 groups: 1) 134 patients who received and tolerated SRL; 2) 604 patients who never received SRL; and 3) 65 patients who started but discontinued SRL. The primary outcome was the development of CAD or CVA beyond 4 months after transplantation with the use of time-dependent Kaplan-Meier analysis. In group 1, there were 6 CAD and 2 CVA events; in group 2, 27 CAD and 16 CVA events; and in group 3, 10 CAD and 2 CVA events. The event-free survival for CAD/CVA at 1, 3, and 5 years was 100%, 98.1%, and 97.2% respectively for group 1; 99.7%, 98.4%, and 96.1% for group 2; and 92.3%, 92.3%, and 85.6% for group 3. On an unadjusted basis, compared with group 2, there was no difference in CAD/CVA rates in group 1 (hazard ratio [HR] 0.92; not significant), but there was an increase in group 3 (HR 2.94; P = .0019). However, on multivariate analysis, only age at transplantation (HR 1.06; P = .001) and diabetes before transplantation (P = .011) were associated with increased CAD/CVA risk. Our analysis showed that patients receiving SRL after LT had no increased risk of CAD/CVA events compared with patients maintained on a calcineurin inhibitor. The risk of CAD/CVA should not be a factor in avoiding SRL. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · Transplantation Proceedings
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    Full-text · Dataset · Feb 2015
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    Full-text · Dataset · Feb 2015
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    Full-text · Dataset · Feb 2015
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    ABSTRACT: Background & aims: Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward. Methods: In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation. Results: Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%). Conclusions: Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844.
    Full-text · Article · Sep 2014 · Gastroenterology
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    ABSTRACT: Unlabelled: Although experimental evidence has indicated that ischemia-reperfusion (I/R) injury of the liver stimulates growth of micrometastases and adhesion of tumor cells, the clinical impact of I/R injury on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has not been fully investigated. To study this issue, we conducted a retrospective review of the medical records of 391 patients from two transplant centers who underwent LT for HCC. Ischemia times along with other tumor/recipient variables were analyzed as risk factors for recurrence of HCC. Subgroup analysis focused on patients with HCC who had pathologically proven vascular invasion (VI) because of the associated increased risk of micrometastasis. Recurrence occurred in 60 patients (15.3%) with median time to recurrence of 0.9 years (range, 40 days-4.6 years). Cumulative recurrence curves according to cold ischemia time (CIT) at 2-hour intervals and warm ischemia time (WIT) at 10-minute intervals showed that CIT>10 hours and WIT>50 minutes were associated with significantly increased recurrence (P=0.015 and 0.036, respectively). Multivariate Cox's regression analysis identified prolonged cold (>10 hours; P=0.03; hazard ratio [HR]=1.9) and warm (>50 minutes; P=0.003; HR=2.84) ischemia times as independent risk factors for HCC recurrence, along with tumor factors, including poor differentiation, micro- and macrovacular invasion, exceeding Milan criteria, and alpha-fetoprotein>200 ng/mL. Prolonged CIT (P=0.04; HR=2.24) and WIT (P=0.001; HR=5.1) were also significantly associated with early (within 1 year) recurrence. In the subgroup analysis, prolonged CIT (P=0.01; HR=2.6) and WIT (P=0.01; HR=3.23) were independent risk factors for recurrence in patients with VI, whereas there was no association between ischemia times and HCC recurrence in patients with no VI. Conclusion: Reducing ischemia time may be a useful strategy to decrease HCC recurrence after LT, especially in those with other risk factors.
    Full-text · Article · Aug 2014 · Hepatology

  • No preview · Article · Aug 2014 · Liver Transplantation
  • W.chacra · A.Weick · A.Kuchipudi · M.Elbatta · G.Divine · C.Barth · D.Moonka
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    ABSTRACT: Sirolimus (SRL) is an immunosuppressive agent used in liver transplantation (LT), in part, to mitigate renal insuffi ciency associated with calcineurin inhibitors (CIs). SRL can cause hyperlipidemia but its association with coronary artery disease (CAD) and cerebrovascular accidents (CVA) is unclear. The purpose of this study is to assess the risk of CAD and CVA associated with the use of SRL in LT recipients. We conducted a chart review of 1053 patients who received a LT at our program between the years 2000 and 2011. Patients with combined liver-kidney transplant, multiple liver transplants, everolimus therapy or post-transplant survival < 3 months were excluded. The remaining 803 patients were divided into 3 groups; 1) 134 patients (16.7%) who received and tolerated SRL; 2) 604 patients (75.2%) who did not receive SRL at any point; and 3) 65 patients (8.1%) who were initiated on SRL but did not tolerate it or discontinued it. The primary composite outcome was the development of CAD or CVA occurring beyond 4 months post-transplant using time dependent Kaplan-Meier analysis. Demographic and transplant data were used to perform multivariate cox regression modeling of signifi cant factors. In Group 1, there were a total of 6 CAD and 2 CVA events, in Group 2, 27 CAD and 16 CVA events, and in Group 3 there were 10 CAD and 2 CVA events. The time dependent event free survival for CAD/CVA at 1, 3 and 5 years was 100%, 98.1% and 97.2% respectively for Group 1; 99.7%, 98.4% and 96.1% for Group 2; and 92.3%, 92.3% and 85.6% for Group 3. On an unadjusted basis, compared to Group 2, there was no difference in CAD/CVA rates in Group 1 (HR 0.92; NS) but there was an increase in CAD/CVA in Group 3 (HR 2.94: p=0.0019). However, on multivariate analysis, the only variables associate with an increase risk of CAD/CVA after LT was age at transplant (HR 1.06; p=0.001) and diabetes prior to transplant (p=0.011). Our analysis shows that patients receiving SRL after LT had no increased risk of CAD/CVA events when compared to patients maintained on a CI. The risk of CAD/CVA should not be a factor in avoiding SRL. Donor age and diabetes prior to transplant are risk factors for CAD/CVA and these patients may warrant closer scrutiny and intervention.
    No preview · Article · Jun 2014 · American Journal of Transplantation
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    Full-text · Article · Mar 2014 · Transplantation
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    Full-text · Dataset · Mar 2014
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    ABSTRACT: To help decrease mortality on the liver transplant waitlist, transplant centers are using living donors (LD) and high risk donors (HRD) in addition to standard risk donors (SRD). HRD is defined as having a donor risk index score higher than 1.6, which suggests a great risk of graft failure. Recent studies have examined survival rates between HRD and SRD recipients; however, little is known about outcomes other than survival, specifically psychosocial outcomes. The purpose of this preliminary, prospective study was to compare post-transplant psychosocial and recovery outcomes between SRD and LD and HRD liver recipients. These outcomes include cognitive functioning, psychological distress, quality of life, and self-reported and objective measures of recovery. Eighty-four patients provided baseline and 6 month post-transplant data. There were generally no statistically significant differences at baseline or the 6 month follow-up suggesting that patients receiving HRD livers have similar outcomes to those who receive SRD livers. However, some effect sizes suggest potential advantages for LD recipients compared to SRD recipients. Transplant centers may be more willing to encourage patients to accept HRD or LD livers knowing that they may have comparable outcomes to SRD recipients, which also has implications for the transplant waitlist.This article is protected by copyright. All rights reserved.
    No preview · Article · Mar 2014 · Clinical Transplantation
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    ABSTRACT: Unlabelled: Lymphocytes play an active role in natural immunity against hepatitis C virus (HCV). We hypothesized that a lower absolute lymphocyte count (ALC) may alter HCV outcome after liver transplantation (LT). The aim of this study was to investigate the impact of peritransplant ALC on HCV recurrence following LT. A total of 289 LT patients between 2005 and 2011 were evaluated. Peritransplant ALC (pre-LT, 2-week, and 1-month post-LT) and immunosuppression were analyzed along with recipient and donor factors in order to determine risk factors for HCV recurrence based on METAVIR fibrosis score. When stratifying patients according to pre- and post-LT ALC (<500/μL versus 500-1,000/μL versus >1,000/μL), lymphopenia was significantly associated with higher rates of HCV recurrence with fibrosis (F2-4). Multivariate Cox regression analysis showed posttransplant ALC at 1 month remained an independent predictive factor for recurrence (P = 0.02, hazard ratio [HR] = 2.47 for <500/μL). When peritransplant ALC was persistently low (<500/μL pre-LT, 2-week, and 1-month post-LT), patients were at significant risk of developing early advanced fibrosis secondary to HCV recurrence (F3-4 within 2 years) (P = 0.02, HR = 3.16). Furthermore, severe pretransplant lymphopenia (<500/μL) was an independent prognostic factor for overall survival (P = 0.01, HR = 3.01). The use of rabbit anti-thymocyte globulin induction (RATG) had a remarkable protective effect on HCV recurrence (P = 0.02, HR = 0.6) despite its potential to induce lymphopenia. Subgroup analysis indicated that negative effects of posttransplant lymphopenia at 1 month (<1,000/μL) were significant regardless of RATG use and the protective effects of RATG were independent of posttransplant lymphopenia. Conclusion: Peritransplant ALC is a novel and useful surrogate marker for prediction of HCV recurrence and patient survival. Immunosuppression protocols and peritransplant management should be scrutinized depending on peritransplant ALC.
    Full-text · Article · Jan 2014 · Hepatology
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    ABSTRACT: Absolute lymphocyte count (ALC) is considered a surrogate marker for the level of immunosuppression and nutritional status of patients and a prognostic factor for survival and recurrence in several cancers. The aim of this study was to investigate the prognostic value of peritransplant ALC for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). HCC patients who underwent LT between 2000 and 2010 were evaluated. Exclusion criteria were combined HCC and cholangiocarcinoma. Peritransplant ALCs (before LT and 2 weeks and 1 month after LT) were analyzed along with tumor, operative, and donor characteristics to identify risk factors for the recurrence of HCC. HCC developed in 27 of the 173 LT patients investigated for risk factors (15.6%). The median time to recurrence was 1.14 years. Low ALCs before and after LT were associated with a higher recurrence rate in a continuous manner (before LT: hazard ratio=1.12, P=0.003; 2 weeks after LT: hazard ratio=1.14, P=0.008; 1 month after LT: hazard ratio=1.06, P=0.055) (increased risk per 100/μL down). On multivariate Cox regression analysis, peritransplant persistent lymphopenia (<1000/μL before LT and <500/μL at 2 weeks and 1 month after LT) was an independent risk factor for cancer recurrence (hazard ratio=7.05, P<0.001), along with tumor characteristics. Peritransplant lymphopenia is a powerful prognostic factor for the recurrence of HCC after LT, which suggests that maintaining ALCs in LT patients might improve cancer outcome.
    Full-text · Article · Nov 2013 · Transplantation
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    ABSTRACT: There has been little research examining the effects of mental health prior to liver transplantation on quality of life and recovery after transplant. Therefore, the purpose of the current study was to examine how pre-transplant depression and anxiety affect mental health, quality of life, and recovery after transplant. Eighty-two transplant recipients completed data when they were listed for transplant and six months post-transplant. Pre-transplant anxiety predicted post-transplant anxiety (p <.001) and there was a trend in predicting post-transplant depression (p =.06). Pre-transplant depression predicted post-transplant depression (p =.03), and there was a trend in predicting post-transplant anxiety (p =.06). Additionally, pre-transplant anxiety predicted post-transplant quality of life for several domains including body pain, role limitations due to emotional problems, mental health, and the mental health composite score (p <.05). However, pre-transplant depression independently predicted outcomes for more domains of quality of life than anxiety, which included physical functioning, role limitations due to physical problems, general health, vitality, social functioning, and the physical composite score (p <.05). Patients with depression at baseline were more likely to report an incomplete recovery 6 months after transplantation (p <.001). With regards to baseline anxiety, there was a trend suggesting that these patients were also more likely to report an incomplete recovery (p =.09). These findings highlight the importance of evaluating transplant candidates both pre- and post-transplant for anxiety and depressive symptoms. Once patients with these symptoms are identified, they can be referred to treatment, which may lead to better post-transplant outcomes for mental health, quality of life, and recovery. Liver Transpl , 2013. © 2013 AASLD.
    Preview · Article · Nov 2013 · Liver Transplantation
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    ABSTRACT: Mycophenolate mofetil (MMF) and sirolimus (SRL) have been used for calcineurin inhibitor (CNI) minimization to reduce nephrotoxicity after liver transplantation. In this prospective, open-label, multicenter study, patients undergoing transplantation from July 2005 to June 2007 who were maintained on MMF/CNI were randomized 4 to 12 weeks after transplantation to receive MMF/SRL (n = 148) or continue MMF/CNI (n = 145). The primary efficacy endpoints were the mean percentage change in the calculated glomerular filtration rate (GFR) and a composite of biopsy-proven acute rejection (BPAR), graft loss, death, and loss to follow-up 12 months after transplantation. Patients were followed for a median of 519 days after randomization. MMF/SRL was associated with a significantly greater renal function improvement from the baseline with a mean percentage change in GFR of 19.7 ± 40.6 (versus 1.2 ± 39.9 for MMF/CNI, P = 0.002). The composite endpoint demonstrated the noninferiority of MMF/SRL versus MMF/CNI (16.4% versus 15.4%, 90% confidence interval = -7.1% to 9.0%). The incidence of BPAR was significantly greater with MMF/SRL (12.2%) versus MMF/CNI (4.1%, P = 0.02). Graft loss (including death) occurred in 3.4% of the MMF/SRL-treated patients and in 8.3% of the MMF/CNI-treated patients (P = 0.04). Malignancy-related deaths were less frequent with MMF/SRL. Adverse events caused withdrawal for 34.2% of the MMF/SRL-treated patients and for 24.1% of the MMF/CNI-treated patients (P = 0.06). The use of MMF/SRL is an option for liver transplant recipients who can benefit from improved renal function but is associated with an increased risk of rejection (but not graft loss). Liver Transpl, 2013. © 2013 AASLD.
    Preview · Article · Jul 2013 · Liver Transplantation
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    ABSTRACT: Background: Venous thromboembolism (VTE) is a potentially fatal complication of major abdominal operations. Liver transplantation is carried out as a treatment for end-stage liver disease (ESLD). It is not well studied whether this population is at increased or decreased risk of a VTE event after a liver transplantation. This study was to determine the frequency of VTE in this population and identify possible predictors. Methods: Retrospective review of 917 patients over 15 years at a single tertiary center was conducted. Liver transplant recipients with symptomatic VTE occurring up to 1 year after liver transplantation were included. Upper and lower extremities deep vein thrombosis (DVT) was identified. The diagnosis of DVT and pulmonary embolism (PE) was made by appropriate diagnostic imaging. Data regarding known risk factors of VTE such as thrombophilia, recent hospitalization, malignancy, and other comorbid conditions were collected. Results: Among 917 patients, a total of 45 events occurred in 42 (4.58%) patients. Twelve had PE and 33 had DVT events. On Cox regression analysis the absence of an alcoholism diagnosis (Hazard Ratio [HR], -0.33; 95% confidence interval [CI], 0.13-0.83), the presence of diabetes (HR, -3.36; 95% CI, 1.76-6.42), a history of VTE (HR, -8.06; 95% CI, 3.37-19.3), and the presence of end-stage renal disease (ESRD; HR, 3.68; 95% CI, 1.34-10.01) were significant predictors of a VTE outcome. No particular diagnosis, history of malignancy, or presence of thrombophilia were associated with increased risk of VTE. Conclusion: The 4.58 % incidence of VTE is comparable with the reported incidence after major abdominal procedures (5%-10%). This data also shows that there is increased risk of VTE in transplant recipients with comorbid conditions of diabetes, previous VTE, and ESRD. This study suggests that a more aggressive strategy for prophylaxis of VTE should be used in liver transplant recipients as with other major abdominal procedures.
    No preview · Article · Sep 2012 · Transplantation Proceedings
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    ABSTRACT: Non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis (CC) are increasing indications for orthotopic liver transplantation (OLT). The aim of this study is to describe our outcomes and delineate predictors of recurrence of NASH and CC after OLT. This is a retrospective study from 1996 to 2008. Donor and recipient demographics, metabolic profile, insulin and steroid intake, immunosuppression regimen, operative factors, outcomes, and pathologies were reviewed. Fisher's exact test, Cox regression models, and Kaplan-Meier plots were used. A total of 83 patients were included. Recurrence occurred in 20 patients. Thirty-four percent of the patients with metabolic syndrome (MS) had recurrence of NASH or CC compared with 13% of the patients without MS (p = 0.05). Recurrence also occurred in 32% of the patients with hypertension (HTN) vs. 12% in those without HTN (p = 0.05). Thirty-seven percent of those on insulin had recurrence vs. 6% of those not on insulin (p = 0.05). Five-yr survival probability for patients with MS, HTN, and insulin use was 52%, 61%, and 58%, respectively. Higher recurrence of NASH and CC was associated with presence of MS, HTN and insulin use. Recurrence should be further evaluated in larger studies, with special emphasis on management of MS and prevention strategies.
    No preview · Article · Sep 2012 · Clinical Transplantation
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    ABSTRACT: Transjugular intrahepatic portosystemic shunt (TIPS) has been fairly effective in managing portal hypertension in the setting of cirrhosis. The aim is to study the safety and efficacy of TIPS in liver transplant (LT) recipients. Fifteen patients underwent TIPS insertion following LT. Indications were refractory ascites (12), hepatic hydrothorax (2), and bleeding esophageal varices (1). Seven patients (46.6%) had complete (C) resolution of ascites, while eight (53.4%) had partial or no (PN) resolution. Portal pressure and portal-right atrial pressure gradients post-TIPS were comparable. Ammonia levels were significantly higher in the PN group. Encephalopathy occurred in two patients (PN group). Four patients required re-transplantation and seven patients expired. The five-yr survival probability was 60.0% for the C group and 66.7% for the PN group. Currently, six patients are alive without clinical evidence of ascites. Two patients are alive but require re-transplantation. TIPS is a safe and effective method to control refractory ascites after LT. Portal pressure changes did not seem to correlate with resolution of ascites. Earlier allograft dysfunction is more likely with PN resolution of ascites after TIPS, and thus early re-transplantation should be considered. Re-transplantation in the context of organ dysfunction and graft failure should be a priority when considering TIPS.
    No preview · Article · Feb 2012 · Clinical Transplantation
  • K.A. Brown · M. Ann Huang · M. Kazimi · D. Moonka

    No preview · Article · Mar 2011
  • M Moeller · A Zalawadia · A Alrayes · G Divine · K Brown · D Moonka
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    ABSTRACT: Several studies have demonstrated mixed results regarding the influence of donor race on patient and graft survival in patients infected with hepatitis C virus (HCV) after liver transplant. However, few studies have looked at the impact of donor race on recurrent HCV. This study is a retrospective analysis of the influence of patient and donor race on the severity of recurrent HCV at a single center. Of patients transplanted at our center between 2000 and 2006, 222 were infected with HCV. Of these, 165 were eligible to be evaluated for recurrent HCV after transplant. We excluded those with patient and graft loss within 1 year that was not related to recurrent HCV, patients with advanced fibrosis from other causes, those who did not undergo posttransplant liver biopsy, and those lost to follow-up. Patients were given a recurrent HCV score of 1, 2, or 3. A score of 1 was assigned if the patient had no more than mild portal fibrosis at 1 year and no bridging fibrosis at any point. A score of 2 was defined as moderate portal fibrosis or focal bridging fibrosis at 1 year or bridging fibrosis or cirrhosis after 3 years. A score of 3 was defined as bridging fibrosis, cirrhosis, or graft loss from HCV within 3 years. Baseline characteristics including donor and recipient age, race, sex, body mass index, ischemia time, hypertension, and diabetes were recorded. Analysis was performed with ordinal multivariate logistic regression modeling. Of the 165 patients with a recurrent HCV score, 105 (64%) had a score of 1, 29 patients (17%) had a score of 2, and 31 patients (19%) had a score of 3. In all, 132 recipients (80%) had white donors, and 26 (16%) had African American donors, 115 patients (70%) were white and 40 (24%) were African American. The mean recurrent HCV scores for the patient donor and recipient race combinations are as follows: white donor and white recipient, 1.54; white donor and African American recipient, 1.89; African American donor and white recipient, 1.18; and African American donor and African American recipient, 1.23. Having a white donor also significantly associated with a higher recurrent HCV score regardless of recipient race (odds ratio 2.93, P = .044) in African American patients, having a white donor had an odds ratio of 4.62 (P = .046). After adjusting for donor age and sex and patient age and sex, having a white donor was still found to be associated with a higher recurrent HCV score (4.48, P = .0275) on multivariate analysis. For all 222 patients, donor race was not associated with overall patient and graft survival. Patients receiving white donor grafts had significantly worse recurrent HCV than those receiving grafts from African American donors regardless of recipient race. This difference was especially marked in African American recipients and persisted on multivariate analysis. These data suggest a graft from a white donor is potentially one more important variable in identifying patients at risk for more aggressive recurrent HCV after orthotopic liver transplant.
    No preview · Article · Dec 2010 · Transplantation Proceedings

Publication Stats

307 Citations
238.78 Total Impact Points

Institutions

  • 1999-2015
    • Henry Ford Hospital
      • • Department of Internal Medicine
      • • Surgery
      Detroit, Michigan, United States
  • 2009-2014
    • Henry Ford Health System
      • Division of Gastroenterology
      Detroit, Michigan, United States
  • 2007
    • Case Western Reserve University
      Cleveland, Ohio, United States