James F Trotter

Baylor University, Waco, Texas, United States

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Publications (172)969.45 Total impact

  • No preview · Article · Dec 2015 · Liver Transplantation
  • J.G. O'Leary · James F. Trotter

    No preview · Article · Dec 2015

  • No preview · Article · Apr 2015 · Journal of Hepatology
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    ABSTRACT: Transplant recipients have elevated cancer risk, perhaps partly due to direct carcinogenic effects of immunosuppressive medications. Experimental evidence indicates that calcineurin inhibitors given to transplant recipients increase cellular expression of transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF), which could promote cancer. To assess the potential role of these pathways in the transplantation setting, we conducted a case-control study nested in a cohort of liver recipients. Cases had nonmelanoma skin cancer (N = 84), cancer of the lung (N = 29), kidney (N = 20), or colorectum (N = 17), or melanoma (N = 3). We selected N = 463 recipients without cancer as controls. TGF-β1 and VEGF levels were measured in sera obtained, on average, approximately 3 years before case diagnosis/control selection. We also measured platelet factor 4 (PF4), a marker of ex vivo platelet degranulation, because TGF-β1 and VEGF can be released from platelets, and we developed a statistical model to isolate the platelet-derived fraction from the remaining circulating component. Compared with controls, lung cancer cases had higher levels of TGF-β1 (median 22.8 vs. 19.4 ng/mL, P = 0.02) and VEGF (277 vs. 186 pg/mL, P = 0.02). However, lung cancer cases also had higher platelet counts (P = 0.08) and PF4 levels (P = 0.02), while residual serum levels of TGF-β1 and VEGF, after accounting for PF4, were unassociated with lung cancer (P = 0.40 and P = 0.15, respectively). Associations were not seen for other cancers. In conclusion, TGF-β1 and VEGF levels were increased in association with lung cancer among transplant recipients, which may be explained by increased platelet counts and platelet degranulation in lung cancer cases. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
    Full-text · Article · Apr 2015 · Cancer Medicine
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    ABSTRACT: Antiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis. The LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir- or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were SVR at 12 weeks (SVR12) and safety. Forty-five patients with advanced fibrosis and 9 with cholestatic hepatitis (74% men, 57% genotype 1a, 63% previous nonresponders) were included. SVR12 occurred in 51% with advanced fibrosis and 44% with cholestatic hepatitis. Extended rapid virologic response was highly predictive of SVR12. Hispanic ethnicity (odds ratio, 0.16; P = 0.03), previous null/partial response (0.24; P = 0.02), IL28B genotype CC (7.0; P = 0.02), albumin (3.87; P = 0.03), platelet count (1.01; P = 0.02), and steroid use (0.21; P = 0.03) were associated with SVR12. Six (11%) patients died, and hepatic decompensation occurred in 22% with advanced fibrosis and 33% with cholestatic hepatitis. Albumin (0.02; P = 0.001), encephalopathy (12.0; P = 0.04) and Hispanic ethnicity (odds ratio, 6.17; P = 0.01) were associated with death or decompensation. For LT recipients with recurrent advanced HCV and at greatest need of cure, protease inhibitor-based triple therapy achieved approximately 50% SVR12. However, there is significant risk of serious adverse events, arguing for earlier intervention. The availability of treatments with better efficacy and safety is of particular importance for posttransplant patients with advanced disease.
    Full-text · Article · Feb 2015 · Transplantation
  • James F Trotter · Luis Lizardo-Sanchez
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    ABSTRACT: Purpose of review: In this review, we discuss the mechanism of action, side-effects, and role of everolimus (EVR) in liver transplant, specifically the most recent de-novo (within 1 month of transplant) and conversion (months to years after transplant) trials in the literature. Recent findings: Everolimus was recently approved by the Food and Drug Administration for use in liver transplantation. Its primary benefit over other immunosuppressive agents is the absence of renal toxicity. De-novo liver recipients receiving EVR with reduced-dose tacrolimus had similar rates of death, graft loss, and rejection compared with tacrolimus monotherapy, but significantly better renal function. The most common side effects are manageable and include stomatitis, hyperlipidemia, and cytopenias. Compared with the other mammalian target of rapamycin inhibitor, sirolimus, EVR is not associated with impaired wound healing or hepatic artery thrombosis. In addition, EVR may provide some benefit as an antineoplastic agent that may be particularly applicable to liver recipients with hepatocellular carcinoma. Summary: Everolimus is the only Food and Drug Administration-approved mammalian target of rapamycin inhibitor for liver transplantation. It offers noninferior immunosuppression (compared with standard therapy) with the absence of renal toxicity. Its use will likely increase over time as clinicians become more familiar with this drug.
    No preview · Article · Sep 2014 · Current Opinion in Organ Transplantation
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    ABSTRACT: Background: In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear. Methods: Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined. Results: Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1. Conclusion: Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.
    No preview · Article · Sep 2014 · Transplantation
  • James F. Trotter
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    ABSTRACT: Living donor liver transplantation is a procedure that has waned in its application over the past decade but remains a beneficial procedure for properly selected candidates. This review discusses some of the newer, relevant studies in the field, focusing on outcomes with hepatocellular carcinoma, ABO-incompatible transplant, and issues in donor complications and safety.
    No preview · Article · Aug 2014 · Clinics in Liver Disease
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    ABSTRACT: Background and Objectives: Left ventricular hypertrophy (LVH) occurs in 12-30% of patients with cirrhosis; however its prognostic significance is not well studied. We assessed the association of LVH with survival in patients undergoing liver transplant (LT) evaluation.Methods: We performed a multicenter cohort study of patients undergoing evaluation for liver transplantation. LVH was defined using transthoracic echocardiography. The outcome of interest was all-cause mortality.Results: LVH was present in 138 (28%) out of 485 patients. Patients with LVH were older and more likely to be male and African American and were more likely to have hypertension. Amongst 345 patients who were not transplanted (212 declined & 133 waiting), 36/110 (33%) patients with LVH died compared to 57/235 (24%) patients without LVH (p=0.23). After LT, 8/28 (29%) patients with LVH died over 3 years compared to 9/112 (8%) patients without LVH (p<0.01). This finding was independent of conventional risk factors for LVH, and all deaths in those with LVH occurred within 9 months of LT. No clinical or demographic characteristics were associated with mortality among LVH patients.Conclusion: The presence of LVH is associated with an early increase in mortality following LT, independent of conventional risk factors for LVH. Further studies are needed to confirm these findings and identify factors associated with mortality following transplantation to improve outcomes. Liver Transpl , 2014. © 2014 AASLD.
    No preview · Article · Jun 2014 · Liver Transplantation
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    ABSTRACT: NS3/4A protease inhibitors, boceprevir or telaprevir, combined with peginterferon and ribavirin was the standard treatment for HCV genotype 1 and remains the only available direct antiviral drug based therapy in some countries. Efficacy and safety data in liver transplant recipients are limited. This was a retrospective cohort study of 81 patients with genotype 1 HCV treated with boceprevir (10%) or telaprevir (90%) plus peginterferon and ribavirin at 6 US transplant centers (53% stage 3-4/4 fibrosis, 57% treatment experienced). The primary end point was undetectable HCV RNA 12 weeks after treatment completion (SVR12). The intent-to-treat SVR12 rate was 63% (51/81). Patients with an extended rapid virologic response, (undetectable HCV RNA at 4 and 12 weeks after starting boceprevir or telaprevir), had a higher rate of SVR12 than all other patients (85% vs. 15%, p<0.001). Adverse effects were common; 21% of patients experienced hemoglobin <8 g/dL and 57% required blood transfusions during the first 16 weeks. Twenty seven percent were hospitalized and 9% died; all were liver-related. The addition of boceprevir or telaprevir to peginterferon and ribavirin yields SVR12 of 63% in liver transplant recipients with genotype 1 recurrent HCV, despite a high prevalence of advanced fibrosis and prior non-response to peginterferon and ribavirin. Rapid virologic response predicted a high likelihood of SVR. Despite a doubling of SVR rates, poor tolerability and high rates of adverse events were frequent and pose barriers to its widespread application.
    No preview · Article · May 2014 · Journal of Hepatology
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    ABSTRACT: Patients with hepatopulmonary syndrome (HPS) are prioritized for liver transplantation (given exception points) due to their high pre- and post-transplant mortality. However, few studies have evaluated outcomes of these patients. We performed a retrospective cohort study using data submitted to United Network for Organ Sharing in a study of the effects of room air oxygenation on pre- and post-transplant outcomes of patients with HPS. We identified thresholds associated with post-transplant survival using cubic spline analysis, and compared overall survival times of patients with and without HPS. From 2002 through 2012, 973 patients on the liver transplant waitlist received HPS exception points. There was no association between oxygenation and waitlist mortality among patients with HPS exception points. Transplant recipients with more severe hypoxemia had increased risk of death after liver transplant. Rates of 3 y unadjusted post-transplant survival were 84% for patients with PaO2 of 44.1-54.0 mm Hg vs 68% for those with PaO2 ≤44.0 mm Hg. In multivariable Cox models, transplant recipients with an initial room-air PaO2≤44.0 mm Hg had significant increases in post-transplant mortality (hazard ratio, 1.58; 95% confidence interval [CI], 1.15-2.18), compared to those with a PaO2 of 44.1-54.0 mm Hg. Overall mortality was significantly lower among waitlist candidates with HPS exception points than those without (hazard ratio, 0.82; 95% CI, 0.70-0.96), possibly because patients with HPS have a reduced risk of pre-transplant mortality and similar rate of post-transplant survival. While there was no association between pre-transplant oxygenation and waitlist survival in patients with HPS MELD exception points, a pre-transplant room-air PaO2 ≤44.0 mm Hg was associated with increased post-transplant mortality. HPS MELD exception patients had lower overall mortality compared to others awaiting liver transplantation, suggesting that the appropriateness of the HPS exception policy should be reassessed.
    No preview · Article · Jan 2014 · Gastroenterology
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    J F Trotter · D Milliner

    Preview · Article · Dec 2013 · American Journal of Transplantation
  • James F Trotter

    No preview · Article · Nov 2013 · Liver Transplantation
  • Mina M Benjamin · Kevin J Dasher · James F Trotter
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    ABSTRACT: The treatment of steroid-resistant rejection (SRR) is associated with severe recurrent hepatitis C virus (HCV) infection after liver transplantation (LTx). After OKT3 was recently withdrawn from the market, thymoglobulin (TG) became the principal treatment for SRR. A retrospective analysis of 32 HCV patients who were treated for SRR with OKT3 (n=15) or TG (n=17) using yearly protocol liver biopsies. Mean follow-up was 4.3 years (OKT3) and 3.2 years (TG). We compared both groups for patient survival, graft loss, and severity of HCV recurrence, manifested as the mean stage of fibrosis (MSF). Patient survival at 1, 2, and 5 years after LTx was 80%, 73%, and 67% in the OKT3 group and 82%, 77%, and 64% in the TG group, respectively. At 2 years after LTx, the graft losses were 3 versus 4 in the OKT3 and TG groups, respectively. At years 1 and 2, the MSF in the OKT3 group was 1.9 and 2.3 versus 2.4 and 2.8 in the TG group, respectively. None of the differences between both groups was statistically significant. There was no significant difference in patient survival, graft loss, or severity of recurrent HCV, measured as MSF, between both groups.
    No preview · Article · Oct 2013 · Transplantation
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    ABSTRACT: Orthotopic liver transplantation (OLT) is the preferred treatment for selected patients with hepatitis B virus (HBV)-related liver disease. This study aimed to (i) define long-term outcomes following OLT for HBV; (ii) to quantify the incidence of HBV recurrence (rHBV) as it relates to anti-HBV treatment; and (iii) to determine outcomes for specific patient subgroups. We performed a retrospective chart review of 738 patients undergoing OLT between 1985 and 2010 at seven US transplant centers and divided the patients into 3 eras, 1985-1994, 1995-2004, and 2005-2010, based on hepatitis B immunoglobulin and antiviral therapies. In Era 3, female gender (p = 0.002), recurrent hepatocellular cancer (p < 0.001), and retransplantation (p = 0.01) were significantly associated with worse survival on multivariate analysis. Survival at three yr was poor for all ethnicities in Era 1, but significantly improved for all except black Americans by Era 3. Era 2 data showed a continued increase in rHBV from five to 10 yr (16.6%, 26.2%). In conclusion, while OLT outcomes have improved because of combination antiviral and immunoglobulin therapy, women and black Americans may not have realized an equal benefit. The rate of rHBV is significant even 10 yr post-transplant with survival affected.
    No preview · Article · Sep 2013 · Clinical Transplantation
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    ABSTRACT: Reinfection with hepatitis B virus (HBV) after liver transplantation (LT) may favor the recurrence of hepatocellular carcinoma (HCC), and combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogues may reduce HBV recurrence after LT. To test associations between HBV, HCC, and survival, we performed a retrospective chart review of patients undergoing LT for HBV between January 1985 and December 2010 at 7 US transplant centers. After we divided the patients into 3 eras based on evolving strategies in antiviral therapy (1985-1994, 1995-2004, and 2005-2010), we reviewed 16 variables to determine whether there were associations between survival and HCC recurrence. Seven hundred thirty-eight patients underwent transplantation for HBV, and 354 (47.7%) had concomitant HCC, which recurred in 58 patients (16.4%). Three-year survival was much better in era 3 versus era 1 (87% versus 40%, P = 0.001), and the incidence of HCC recurrence was lower (12% versus 29%, P = 0.009). The lungs were the most frequent first site of HCC recurrence, and they were followed by the liver. A multivariate analysis showed that HBV reinfection, HCC recurrence, and HBIG use were associated with worse survival (P < 0.001, P < 0.001, and P = 0.002, respectively); HCC recurrence and stage 3 HCC, among other factors, were associated with HBV reinfection (P < 0.001 and P = 0.004); and stage 3 HCC, vascular invasion of the explanted tumor, and post-LT chemotherapy were associated with HCC recurrence (P = 0.008, P < 0.001, and P < 0.001, respectively). Patients with HBV reinfection were 3.6 times more likely than patients without HBV to have HCC recurrence. These data suggest further study of attempts at LT for patients with HBV and HCC beyond the Milan criteria if their HBV is aggressively and successfully treated. Liver Transpl, 2013. © 2013 AASLD.
    No preview · Article · Sep 2013 · Liver Transplantation
  • James F Trotter · Monica Grafals · Angel E Alsina
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    ABSTRACT: Renal dysfunction is a critical issue for liver transplant candidates and recipients. Acute and chronic nephrotoxicity, however, are the compromise for the potent immunosuppression provided by calcineurin inhibitors (CNIs). To maintain graft and patient survival afforded by CNIs while minimizing renal dysfunction in liver transplant patients, the reduction, delay, or elimination of CNIs in immunosuppression regimens is being implemented more frequently by clinicians. The void left by standard-dose CNIs is being filled by nonnephrotoxic immunosuppressants such as the mycophenolates and mammalian target of rapamycin (mTOR) inhibitors. Results of studies of renal-sparing regimens in liver transplant recipients have been inconsistent, which may be explained upon closer examination of several study-related factors including study design and duration of follow-up. Liver Transpl, 2013. © 2013 AASLD.
    No preview · Article · Aug 2013 · Liver Transplantation
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    ABSTRACT: Background: Despite its importance, determination of competence to consent to organ donation varies widely based on local standards. We piloted a new tool to aid transplant centers in donor assessment. Methods: We assessed competence-related abilities among potential living liver donors (LDs) in the nine-center A2ALL study. Prospective LDs viewed an educational video and were queried to assess Understanding, Appreciation, Reasoning, and ability to express a Final Choice using the MacArthur Competence Assessment Tool for Clinical Research, adapted for computerized administration in LDs ("MacLiver"). Videotaped responses were scored by a clinical neuropsychologist (JF). Results: Ninety-three LDs were assessed. Mean (standard deviation; domain maximum) scores were as follows: Understanding: 18.1 (2.6; max = 22), Appreciation: 5.1 (1.0; max = 6), Reasoning: 3.1 (0.8; max = 4), and Final Choice: 3.8 (0.5; max = 4). Scores did not differ by demographics, relationship to the recipient, eligibility to donate, or eventual donation (p > 0.4). Higher education was associated with greater Understanding (p = 0.004) and Reasoning (p = 0.03). Conclusion: Standardized, computerized education with independent ratings of responses may (1) alert the clinical staff to potential donors who may not be competent to donate and (2) highlight areas needing further assessment and education, leading to better informed decision making.
    Full-text · Article · Jul 2013 · Clinical Transplantation
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    ABSTRACT: Background: Few studies have evaluated the accuracy of United Network for Organ Sharing (UNOS) or Scientific Registry of Transplant Recipients data among patients listed for liver transplantation. Of particular importance for transplant policy and practice is whether patients' outcomes are coded properly. Methods: Using data from four transplant centers, we identified all liver transplant candidates removed from the waitlist from February 27, 2002 to July 24, 2010, with a specific focus the removal code of "other." Results: Among nontransplanted patients at these centers, 2206 patients were removed for death or clinical deterioration. Of these, 8.6% (189 of 2206) were misclassified; they were assigned the UNOS removal code of "other." Among these 189 misclassified patients, 128 became medically unsuitable, 35 died, and 26 became too sick to transplant. Nearly one-half (46.8%) of misclassified patients were removed due to advanced hepatocellular carcinoma. Among true waitlist removals for death, only 35 of 1593 (2.2%) were misclassified. Conversely, of true removals for clinical deterioration, 154 of 612 (25.2%) were misclassified, with significant (P < 0.001) center variation: 4.4% (Baylor), 8.0% (Georgetown), 32.6% (University of Pennsylvania), and 45.0% (Mount Sinai). Extrapolating these data to the entire United States, if "other" patients who truly died or clinically deteriorated were recoded appropriately, there would be an additional 2525 (95% confidence interval, 2046-3102) patients removed from the waitlist due to death (331) or clinical deterioration (2194) since 2002. Discussion: A substantial proportion of patients truly removed from the waitlist for death or clinical deterioration were misclassified as "other." Thus, analyses using the UNOS or the Scientific Registry of Transplant Recipients database may underestimate the true proportion of patients removed from the waitlist for clinical deterioration.
    No preview · Article · Jun 2013 · Transplantation
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    Full-text · Article · Apr 2013 · Journal of Hepatology

Publication Stats

5k Citations
969.45 Total Impact Points


  • 2009-2015
    • Baylor University
      Waco, Texas, United States
    • Tufts Medical Center
      • Department of Medicine
      Boston, MA, United States
  • 2002-2013
    • University of Colorado
      • • Department of Surgery
      • • Department of Medicine
      • • Division of Gastroenterology and Hepatology
      Denver, Colorado, United States
  • 2009-2012
    • Baylor Health Care System
      • Internal Medicine
      Dallas, Texas, United States
  • 2011
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 2005-2008
    • University of Colorado Hospital
      • Department of Medicine
      Denver, Colorado, United States
  • 2007
    • CUNY Graduate Center
      New York, New York, United States