Michael G Hughes

Medical University of South Carolina, Charleston, South Carolina, United States

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Publications (4)17.12 Total impact

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    ABSTRACT: We examined the long-term outcome of transplantation for alpha 1-antitrypsin deficiency (A1ATD). Data were reviewed on 42 transplants in 35 children with A1ATD over 42 yr and compared with 129 transplants in 116 children with biliary atresia (BA). Over 50% of patients were followed up for >10 yr. A1ATD were older than BA at transplantation, median age, 6.0 vs. 1.0 yr (p < 0.0001), and transplanted earlier in the course of liver failure (total bilirubin, 2.7 mg/dL [1.4-6.9] vs. 9.7 mg/dL [2.9-15.4], p = 0.005). Patient survival was greater in A1ATD than BA: one-yr post-transplant, 82.7% vs. 67.9%; five yr, 76.5% vs. 60.2%; and 10 yr, 76.5% vs. 55.9% (p = 0.03). Death-censored graft survival was similar: one-yr post-transplant, 68.4% vs. 66.2%; five yr, 68.4% vs. 55.8%; and 10 yr, 68.4% vs. 52.5% (p = 0.2). Deaths were from infection, hemorrhage, and graft failure <6 months post-transplant. Patient survival improved at five yr from 33.3% pre-cyclosporine (CSA) (1969-1984) (n = 6) to 76.5% in the CSA era (1985-1994) (n = 17) and 100% with tacrolimus (1995-2006) (n = 12) (p = 0.007). The age at transplantation and the degree of liver dysfunction were related to the differences in graft and patient survival between A1AT and BA.
    Clinical Transplantation 11/2010; 25(5):731-6. DOI:10.1111/j.1399-0012.2010.01371.x · 1.49 Impact Factor
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    ABSTRACT: Hepatitis C Virus (HCV) is a major public health concern, with no effective vaccines currently available and 3% of the world's population being infected. Despite the existence of both B- and T-cell immunity in HCV-infected patients, chronic viral infection and HCV-related malignancies progress. Here we report the identification of a novel HCV TCR from an HLA-A2-restricted, HCV NS3:1073-1081-reactive CTL clone isolated from a patient with chronic HCV infection. We characterized this HCV TCR by expressing it in human T cells and analyzed the function of the resulting HCV TCR-transduced cells. Our results indicate that both the HCV TCR-transduced CD4(+) and CD8(+) T cells recognized the HCV NS3:1073-1081 peptide-loaded targets and HCV(+) hepatocellular carcinoma cells (HCC) in a polyfunctional manner with cytokine (IFN-gamma, IL-2, and TNF-alpha) production as well as cytotoxicity. Tumor cell recognition by HCV TCR transduced CD8(-) Jurkat cells and CD4(+) PBL-derived T cells indicated this TCR was CD8-independent, a property consistent with other high affinity TCRs. HCV TCR-transduced T cells may be promising for the treatment of patients with chronic HCV infections.
    PLoS Pathogens 07/2010; 6(7):e1001018. DOI:10.1371/journal.ppat.1001018 · 8.06 Impact Factor
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    ABSTRACT: Cytomegalovirus (CMV) is a significant cause of morbidity, mortality, and cost in solid organ transplant recipients. This study was conducted to measure both the clinical efficacy and the pharmacoeconomic impact of implementing, as standard of care, an abbreviated preemptive monitoring strategy compared with universal prophylaxis in a large teaching hospital. This prospective observational study included only recipients at moderate risk for CMV infection, specifically recipients who were CMV seropositive before transplant. Recipients transplanted between February 2006 and December 2006 received prophylactic valganciclovir for 90 days after transplant, and those transplanted between January 2007 and December 2007 were enrolled in a preemptive monitoring strategy that included no anti-CMV prophylaxis but instead used serial CMV polymerase chain reactions in weeks 4, 6, 8, 10, 12, 16, 20, and 24 to monitor the development of CMV DNAemia. Costs were analyzed from a societal perspective. A total of 130 patients were included in this study. Baseline and transplant demographics are well matched between groups. CMV syndrome occurred in three patients in each group, and one patient in the preemptive group developed CMV disease. Thirty-seven percent of patients in the preemptive group developed CMV DNAemia, 68% of these patients received antiviral therapy. Personnel and laboratory monitoring costs were significantly higher in the preemptive group, whereas medication cost was significantly higher in the prophylaxis group. Although outcomes and the overall cost of (1) universal prophylaxis and (2) preemptive monitoring are similar, universal prophylaxis places the cost burden on the patient whereas preemptive monitoring shifts the cost burden to the healthcare system.
    Transplantation 05/2010; 89(10):1218-23. DOI:10.1097/TP.0b013e3181d54ba6 · 3.78 Impact Factor
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    Michael G Hughes, Hugo R Rosen
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    ABSTRACT: Hepatitis C is a leading etiology of liver cancer and a leading reason for liver transplantation. Although new therapies have improved the rates of sustained response, a large proportion of patients (approximately 50%) fail to respond to antiviral treatment, thus remaining at risk for disease progression. Although chimpanzees have been used to study hepatitis C virus biology and treatments, their cost is quite high, and their use is strictly regulated; indeed, the National Institutes of Health no longer supports the breeding of chimpanzees for study. The development of hepatitis C virus therapies has been hindered by the relative paucity of small animal models for studying hepatitis C virus pathogenesis. This review presents the strengths of human liver transplantation and highlights the advances derived from this model, including insights into viral kinetics and quasispecies, viral receptor binding and entry, and innate and adaptive immunity. Moreover, consideration is given to current and emerging antiviral therapeutic approaches based on translational research results.
    Liver Transplantation 11/2009; 15(11):1395-411. DOI:10.1002/lt.21866 · 3.79 Impact Factor