Christopher Hughes

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (6)41.61 Total impact

  • Mi Li · Yang Zhao · Abhinav Humar · Amit D. Tevar · Christopher Hughes · Raman Venkataramanan
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    ABSTRACT: Introduction: Limited information is available on the pharmacokinetics of drugs in the donors and recipients following adult living donor liver transplantation (LDLT). Given that both the donors and recipients receive multiple drug therapies, it is important to assess the pharmacokinetics of drugs used. Areas covered: Pathophysiological changes that occur post-surgery and regulatory factors that may influence pharmacokinetics of drugs, especially hepatic drug metabolism and transport in both LDLT donors and the recipients are discussed. Pharmacokinetic data in animals with partial hepatectomy are presented. Clinical pharmacokinetic data of certain drugs in LDLT recipients are further reviewed. Expert opinion: It takes up to six months for the liver volume to return to normal after LDLT surgery. In the LDLT recipients, drug exposure generally is higher with lower clearance during early period post-transplant; lower initial dosages of immunosuppressants are used than deceased donor liver transplant recipients during the first six months post-transplantation. In animals, the activities of hepatic drug metabolizing enzymes and transporters are known to be altered differentially during liver regeneration. Future studies on actual hepatic function with reference to drug metabolism and transport, and the biliary secretory function in both LDLT patient populations are required.
    No preview · Article · Jan 2016 · Expert Opinion on Drug Metabolism & Toxicology

  • No preview · Article · Apr 2015 · Gastroenterology

  • No preview · Article · Apr 2015 · Gastroenterology
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    ABSTRACT: In the setting of liver transplantation, mycophenolate mofetil (MMF) may be used as an adjuvant therapy for immunosuppression to prevent graft rejection; however, its use may be limited due to severe gastrointestinal (GI) side-effects. In contrast, enteric-coated mycophenolate sodium (EC-MPS) may be associated with less severe side-effects and hence, better tolerability. We compared the side-effects of EC-MPS to MMF in liver transplant patients in a de novo study (Study I—randomized, prospective, double-blinded) and a conversion study (Study II). In both studies, the severity of GI symptoms was assessed at various time points using the Gastrointestinal Symptoms Rating Scale (GSRS) survey, a validated survey of GI symptoms (abdominal pain, reflux, indigestion, diarrhea, and constipation). In Study I, the symptoms of 30 recipients receiving EC-MPS (n=15) were compared to 15 recipients receiving MMF. A multivariate analysis of variance (MANOVA) of the total GSRS scores and symptom syndrome sub-scores revealed no significant difference (p>0.05) between the two medications over time. A conversion study (Study II) with 29 participants, however, showed that over time, all GI symptoms improved significantly (p<0.001) when the patients were treated with EC-MPS instead of MMF.This article is protected by copyright. All rights reserved.
    No preview · Article · Apr 2014 · Clinical Transplantation
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    ABSTRACT: Posttransplant lymphoproliferative disorder (PTLD) is a well-established complication of immunosuppression. The involvement of the gastrointestinal (GI) tract occurs in 25% of all cases of PTLD. Fortunately, surgical intervention is seldom required. We report our experience of surgical treatment of complicated GI-PTLD after liver transplantation (LTx). A retrospective analysis of 5677 adult patients who underwent LTx between 1983 and 2009 was conducted. Thirty-six patients presented with GI-PTLD. Sixteen patients presented with complications associated with GI-PTLD requiring emergency surgery. The average (SD) time from LTx to GI surgery was 7.9 (5.8) years (range, 4 months to 17 years). Indications for surgical intervention were small bowel obstruction (seven cases), perforation (six cases), and GI bleeding (three cases). Most GI-PTLD occurred in the small bowel or right colon (81%). In addition to the surgery, treatment of PTLD consisted of reduction of immunosuppression, use of rituximab (n=10), and systemic chemotherapy (n=7). Overall mortality was 69%, with most of the deaths occurring within 8 months after emergency laparotomy. GI bleeding and perforation were associated with higher mortality (>66%). Despite higher early mortality in the surgical group, no differences on long-term outcome were observed between patients with GI-PTLD who required surgery and those who did not (P=0.371). In summary, GI-PTLD requiring surgical intervention is an extremely rare condition with high early mortality. Most of the cases are monoclonal, present a late onset, and involve the lower GI tract. Intestinal obstruction is the main indication for surgical intervention and is associated with better prognosis.
    No preview · Article · Jul 2012 · Transplantation
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    ABSTRACT: As with other programs across the country, at the University of Pittsburgh liver transplantation continues to evolve after three decades. The shortage of organs represents the biggest problem in the field, and in response there has been an increase in the number of expanded-criteria-donor transplants and other methods to expand the donor pool such as live-donor, domino, and split-liver transplants. As the program has matured, we have seen an increasing number of recipients needing re-transplantation because--unlike with kidney transplants--recurrence of disease represents a significantly greater problem than immunologic graft failure. Modern immunosuppression, especially with agents such as tacrolimus, have significantly reduced the immunologic problems associated with liver transplantation. But as survival rates have improved and patients are living longer after transplant, the problems associated with long-term immunosuppression have become increasingly important. Our program, along with others, continues to look at methods to minimize the overall amount of long-term immunosuppression to which patients are exposed.
    No preview · Article · Jan 2011 · Clinical transplants