John P Roberts

St. Elizabeth's Medical Center, Boston, Massachusetts, United States

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Publications (185)973.72 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies on loco{\hyphen}regional therapy (LRT) and alpha{\hyphen}fetoprotein (AFP) in predicting outcome after liver transplant (LT) for hepatocellular carcinoma (HCC) have shown inconsistent results. We analyzed the OPTN database in Region 5 from January 2004 to January 2009, and performed univariate and multivariate analysis of 11 pre{\hyphen}transplant recipient and donor variables in 1074 patients with HCC meeting Milan criteria to detect association with post{\hyphen}LT tumor recurrence or mortality. Mean waitlist time was 438 days. The 1{\hyphen} and 5{\hyphen}year post{\hyphen}LT survival was 91.1{\percnt} and 71.1{\percnt}, respectively. In multivariate analysis, AFP before LT was the only predictor of HCC recurrence. The association between AFP and HCC recurrence was observed only in the subgroup receiving LRT but not in the subgroup without LRT. Predictors of mortality in multivariate analysis were HCC recurrence, Donor Risk Index, last AFP before LT, and MELD score. AFP before LT was the strongest predictor of post{\hyphen}transplant HCC recurrence or death in multivariate analysis. In conclusion, in Region 5 with prolonged waitlist time, high AFP was the only pre{\hyphen}transplant variable predicting post{\hyphen}transplant tumor recurrence and mortality for HCC meeting Milan criteria. Our results also supported the importance of the effects of LRT on AFP in predicting prognosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Transplantation 03/2015; 29(6). DOI:10.1111/ctr.12542 · 1.49 Impact Factor
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    ABSTRACT: We report long-term intention-to-treat outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing down-staging to within Milan/UNOS T2 criteria before liver transplantation (LT) since 2002, and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The down-staging subgroups include 1 lesion >5 cm and ≤8 cm (n=43), 2 or 3 lesions at least one >3 cm and ≤5 cm with total tumor diameter ≤8 cm (n=61), or 4 to 5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n=14). In the down-staging group, 64 patients (54.2%) had received LT, and 5 (7.5%) developed HCC recurrence. Two of the 5 patients with HCC recurrence had 4-5 tumors at presentation. The 1- and 2-year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the down-staging group, versus 20.3% and 25.6% in the T2 group (p=0.04). The Kaplan-Meier 5-year post-transplant survival and recurrence-free probabilities were 77.8% and 90.8%, respectively, in the down-staging group, versus 81% and 88%, respectively, in the T2 group (p=0.69 and p=0.66, respectively). The 5-year intention-to-treat survival was 56.1% in the down-staging group, versus 63.3% in the T2 group (p=0.29). Factors predicting dropout in the down-staging group included pre-treatment alpha-fetoprotein ≥1000 ng/mL (multivariate HR 2.42, p=0.02) and Child's B versus Child's A cirrhosis (multivariate HR 2.19, p=0.04). Conclusion: Successful down-staging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post-transplant survival, comparable to those meeting T2 criteria without down-staging. Due to the small number of patients with 4-5 tumors, further investigations are needed to confirm the efficacy of down-staging in this subgroup. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases.
    Hepatology 02/2015; 61(6). DOI:10.1002/hep.27752 · 11.19 Impact Factor
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    ABSTRACT: Background: The U.S. liver allocation system effectively prioritizes most liver transplant candidates by disease severity as assessed by the Model for End-Stage Liver Disease (MELD) score. Yet, one in five dies on the wait-list. We aimed to determine whether clinician assessments of health status could identify this subgroup of patients at higher risk for wait-list mortality. Methods: From 2012-13, clinicians of all adult liver transplant candidates with laboratory MELD≥12 were asked at the clinic visit: “How would you rate your patient's overall health today (0=excellent, 5=very poor)?” The odds of death/delisting for being too sick for transplant by clinician-assessment score ≥3 vs. <3 were assessed by logistic regression. Results: 347 liver transplant candidates (36% female) had a mean follow-up of 13 months. Men differed from women by disease etiology (<0.01) but were similar in age and markers of liver disease severity (p>0.05). Mean clinician assessment differed between men and women (2.3 vs. 2.6; p=0.02). The association between clinician-assessment and MELD was ρ=0.28 (p<0.01). 53/347 (15%) died/were delisted. In univariable analysis, a clinician-assessment score≥3 was associated with increased odds of death/delisting (2.57; 95% CI 1.42-4.66). After adjustment for MELD and age, a clinician-assessment score≥3 was associated with 2.25 (95% CI 1.22-4.15) times the odds of death/delisting compared to a clinician-assessment score<3. Conclusions: A standardized clinician assessment of health status can identify liver transplant candidates at high risk for wait-list mortality independent of MELD score. Objectifying this “eyeball test” may inform interventions targeted at this vulnerable subgroup to optimize wait-list outcomes.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 01/2015; DOI:10.1111/liv.12792 · 4.41 Impact Factor
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    ABSTRACT: A subset of liver transplant (LT) recipients who undergo transplant for hepatocellular carcinoma (HCC) will develop post-operative recurrence. There has yet to be a thorough investigation of donor factors influencing recurrence. Data regarding adult, primary LT recipients with HCC (n=5002) transplanted between January 1, 2006 and September 30, 2010 were extracted from United Network for Organ Sharing (UNOS) database, with subsequent estimation of the cumulative incidence of post-LT recurrence by donor factors. Of the HCC LT recipients, 324 (6.5%) developed recurrence. Analysis of donor characteristics demonstrated a higher cumulative incidence of recurrence within 4 years of transplant among recipients of donors ≥60 years old (versus donors <60 years old) (11.8% versus 7.3%, respectively; p<0.001), and donors from non-local share distribution (versus local share distribution) (10.6% versus 7.4%, respectively; p=0.004). The latter two findings held true on multivariable analysis with HCC recurrence risk increased by 70% for recipients of donor livers ≥60 years old (SHR=1.70, 95% CI 1.31-2.20, p<0.001) and by 42% for recipients of non-local share distribution (SHR=1.42, 95% CI 1.09-1.84, p=0.009) after adjusting for clinical characteristics. In conclusion, consideration of certain donor factors may reduce the cumulative incidence of post-transplant HCC recurrence, and thus improve long-term survival following LT. Liver Transpl , 2014. © 2014 AASLD.
    Liver Transplantation 11/2014; 21(2). DOI:10.1002/lt.24042 · 3.79 Impact Factor
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    ABSTRACT: Liver transplant allocation policy does not give MELD exception points for patients with a single hepatocellular carcinoma (HCC) less than 2cm in size, but does give points to patients with multiple small nodules. Because standard-of-care imaging for HCC struggles to differentiate HCC from other nodules, it is possible that a subset of patients receiving liver transplant for multiple nodules <2cm in size do not have HCC.We evaluate risk of post-transplant HCC recurrence and waitlist dropout for patients with multiple small nodules using competing risks regression based on the Fine and Gray model.We identified 5002 adult HCC patients in the OPTN/UNOS dataset diagnosed and transplanted between January 2006 and September 2010. Compared to patients with >1 tumor <2cm, risk of developing recurrence was significantly higher in patients with 1 or more tumors with only 1 tumor ≥2cm (SHR 1.63, p=0.009), as well as in patients with 2-3 tumors ≥2cm (SHR 1.84, p=0.02). Dropout risk was not significantly different among size categories.HCC recurrence risk was significantly lower in patients with multiple nodules <2cm in size than in those with larger tumors, supporting the possibility that some patients received unnecessary transplants. The priority given to these patients must be re-examined.This article is protected by copyright. All rights reserved.
    Clinical Transplantation 11/2014; DOI:10.1111/ctr.12480 · 1.49 Impact Factor
  • Liver Transplantation 10/2014; 20(10):1285-1285. DOI:10.1002/lt.23982 · 3.79 Impact Factor
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    ABSTRACT: Serum alpha-fetoprotein (AFP) has been increasingly recognized as a marker for poor prognosis after liver transplant (LT) for hepatocellular carcinoma (HCC). Many published reports, however, included a large proportion of HCC beyond Milan criteria, and the effects of incorporating AFP as an exclusion criterion for LT remain unclear. We studied 211 consecutive patients receiving LT for HCC within Milan criteria by imaging under the MELD organ allocation system between June 2002 and January 2009. The majority (93.4%) had loco-regional therapy before LT. The median follow-up was 4.5 years (minimum > 2 years). The Kaplan-Meier 1- and 5-year patient survival was 94.3% and 83.4%. In univariate analysis, significant predictors of HCC recurrence included vascular invasion (HR 10.0, 95% CI 3.9-26, p<0.0001), pathologic tumor stage beyond UCSF criteria (HR 4.1, 95% CI 3.9-26, p=0.012), AFP >1000 ng/mL (HR 4.5, 95% CI 1.3-15.4, p=0.018); and AFP >500 ng/mL (HR 3.1, 95% CI 1.04-9.4, p=0.043). In multivariate analysis, vascular invasion was the only significant predictor of tumor recurrence (HR 4.5, 95% CI 1.3-15.4, p=0.018). AFP >1000 ng/mL was the strongest pre-transplant variable predicting vascular invasion (Odds ratio 6.8, 95% CI 1.6-19.1, p=0.006). The 1- and 5-year survival without recurrence for patients with AFP >1000 ng/mL was 90% and 52.7%, respectively, vs. 95% and 80.3% for AFP <=1000 ng/mL (p=0.01). Applying an AFP cutoff of >1000 ng/mL would have resulted in exclusion of 4.7% of patients from LT, and a 20% reduction in HCC recurrence. In conclusion, AFP >1000 ng/mL may be a surrogate for vascular invasion and predicts post-transplant HCC recurrence. Incorporating AFP >1000 ng/mL as an exclusion criterion for LT using Milan criteria may further improve post-transplant outcome. Liver Transpl , 2014. © 2014 AASLD.
    Liver Transplantation 08/2014; 20(8). DOI:10.1002/lt.23904 · 3.79 Impact Factor
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    ABSTRACT: BACKGROUND: Geographic disparity in access to liver transplantation (LT) exists. This study sought to examine Model for End-Stage Liver Disease-era multiply listed (ML) LT candidate (ie, candidates who list at 2 or more LT centers to receive a liver transplant). STUDY DESIGN: Data on adult, primary, non-status 1 LT candidates (n = 59,557) listed from January 1, 2005 to December 31, 2011 were extracted from the United Network for Organ Sharing's Standard Transplant Analysis and Research files. Comparisons of ML vs singly listed LT candidates were performed, with additional analysis performed at the donor service area (DSA) and regional level, as well as assessment of the donor population used. RESULTS: There were 1,358 (2.3%) ML candidates during the 7-year study period. Multiply listed candidates compared with singly listed candidates were more often male, white, blood type O, nondiabetic, college educated, and privately insured. The odds of pursuing ML increased considerably as time on the waitlist increased. Of the ML candidates, 918 (67.6%) went on to receive a liver transplant (ML-LT), 767 (83.6%) at the secondary listing DSA, which was a median of 588 miles (range 229 to 1095 miles) from the primary listing DSA. When compared with the primary listing DSA, the secondary listing DSA had significantly lower match Model for End-Stage Liver Disease scores, as well as shorter wait times. Regional analysis demonstrated significantly higher odds for pursuing ML from LT candidates located within regions 1, 5, and 9. CONCLUSIONS: A small and distinctive cohort of LT candidates pursue ML, indicating willingness and means to travel to receive a liver transplant. Efforts toward equalizing LT access across regional disparities are warranted, and can help obviate the need for ML. (C) 2014 by the American College of Surgeons
    Journal of the American College of Surgeons 05/2014; 219(3). DOI:10.1016/j.jamcollsurg.2014.03.048 · 4.45 Impact Factor
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    ABSTRACT: Background Geographic disparity in access to liver transplantation (LT) exists. This study sought to examine the MELD era multiply-listed (ML) LT candidate- candidates who list at two or more LT centers in order to achieve LT. Study Design Data regarding adult, primary (1°), non-status 1, LT candidates (n=59,557) listed from 1/1/05 to 12/31/11 were extracted from UNOS STAR files. Comparisons of ML versus singly listed (SL) LT candidates were performed, with further analysis performed at the Donor Service Area (DSA) and regional level, as well as assessment of the donor population utilized. Results There were 1,358 (2.3%) ML candidates during the 7 year study period. ML compared to SL candidates were more often male, white, blood type O, non-diabetic, college educated, and privately insured. The odds of pursuing ML significantly increased as time on the waitlist increased. Of the ML candidates, 918 (67.6%) went on to receive a LT (ML-LT), 767 (83.6%) at the 2° listing DSA which was a median (IQR) of 588 miles (229-1095) from the 1° listing DSA. When compared to the 1° listing DSA, the 2° listing DSA had significantly lower match MELD scores as well as shorter wait times. Regional analysis demonstrated significantly higher odds for pursuing ML from LT candidates located within Regions 1, 5, and 9. Conclusions A small and distinctive cohort of LT candidates pursue ML, indicating willingness and means to travel to achieve LT. Efforts towards equalizing LT access across regional disparities are warranted, and may help obviate the need for ML.
    Journal of the American College of Surgeons 01/2014; · 4.45 Impact Factor
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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.
    Liver Transplantation 07/2013; 19(7). DOI:10.1002/lt.23658 · 3.79 Impact Factor
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    ABSTRACT: OBJECTIVE. The purpose of this article is to investigate the determinants of second-order bile duct visualization at CT cholangiography in living potential liver donors. MATERIALS AND METHODS. We retrospectively identified 143 potential living liver donors (83 men and 60 women; mean age, 37 years) evaluated with CT cholangiography, which included a slow infusion of iodipamide meglumine with CT acquisition 15 minutes after biliary contrast agent administration. Two readers independently scored the visualization of the second-order bile duct branches on a previously established 4-point scale (0 = not seen, 1 = faintly seen, 2 = well seen, and 3 = excellent visualization). Multivariate analysis was used to investigate the correlation between visualization scores and potential determinants of second-order bile duct opacification, specifically age, body mass index, creatinine level, total and direct bilirubin levels, alkaline phosphatase level, aspartate aminotransferase level, alanine aminotransferase level, patient maximum linear width, CT noise, and hepatosplenic attenuation difference at unenhanced CT. RESULTS. The mean (± SD) second-order bile duct visualization scores were 2.35 ± 0.66 and 2.55 ± 0.60 for readers 1 and 2, respectively. In the multivariate analysis, the only independent predictors of reduced second-order bile duct visualization were higher alkaline phosphatase level (p = 0.01) and higher CT noise (p = 0.02). CONCLUSION. Higher serum alkaline phosphatase level and higher CT noise in potential living liver donors indicate a higher risk of poor second-order bile duct visualization at CT cholangiography.
    American Journal of Roentgenology 05/2013; 200(5):1028-33. DOI:10.2214/AJR.11.8364 · 2.74 Impact Factor
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    ABSTRACT: BACKGROUND: Successful left lateral segment (sectionectomy) and right trisegmentectomy (trisectionectomy) split-liver transplantation (SLT) have been achieved. However, there are few reports of the use of true right/left splitting in SLT. METHODS: A single-centre retrospective review of true right/left ex vivo split-liver transplants performed during the period 1993-2010 was conducted. Nine cadaveric liver grafts underwent splitting and the resultant 18 allografts were used in transplants performed at the study centre. RESULTS: In the nine right lobe recipients, 10-year patient and graft survival rates were both 74%. There were no vascular complications, one biliary complication and one re-exploration. In the nine left lobe recipients, 10-year patient and graft survival rates were 78% and 66%, respectively. Postoperative complications included six biliary complications, four of which required surgical revision and all of which occurred within 5 months of transplantation, and two vascular complications, including one early hepatic artery thrombosis (HAT) and one late HAT, one of which required retransplantation. Five left lobe recipients required re-exploration, and one patient developed small-for-size syndrome following SLT, which resolved with conservative measures. CONCLUSIONS: True right/left ex vivo SLT remains a viable option for facilitating the expansion of the adult cadaver donor pool and allows for excellent patient and graft survival. Postoperative morbidity remains high, especially in recipients of the left lobe graft, and must be balanced with the benefits to be derived from transplant.
    HPB 04/2013; 16(3). DOI:10.1111/hpb.12113 · 2.05 Impact Factor
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    ABSTRACT: Latent tuberculosis infection is an important problem for solid organ transplant recipients because of the frequency of its occurrence and its potential for reactivation. Because of the high mortality rate associated with active tuberculosis infections in transplant recipients, guidelines from the American Thoracic Society recommend treatment for latent tuberculosis in this population. However, the choice of treatments is often difficult because liver transplant recipients may be more sensitive to isoniazid hepatotoxicity, and rifampin has significant drug interactions with the calcineurin inhibitors used for immunosuppression. Two prior case reports described success with the use of rifabutin, a rifampin alternative, as part of a multidrug treatment regimen for active tuberculosis in posttransplant patients; however, there is no prior literature describing any experience with rifabutin for the treatment of latent tuberculosis in the posttransplant setting. We present a summary of tacrolimus drug levels and corresponding dose requirements for a single posttransplant patient during the administration of 3 different latent tuberculosis drug regimens: rifampin alone, rifampin plus ketoconazole, and rifabutin. In this patient's case, rifabutin allowed the maintenance of adequate tacrolimus levels, although an approximate 2.5-fold increase in the dose was required. Rifampin alone was associated with inadequate immunosuppressant levels, and rifampin plus ketoconazole was associated with a problematically prolonged QT interval and concerns about inadequate tuberculosis treatment. Liver Transpl 19:457-461, 2013. © 2013 AASLD.
    Liver Transplantation 04/2013; 19(4). DOI:10.1002/lt.23622 · 3.79 Impact Factor
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    ABSTRACT: We previously reported that national liver distribution is highly concentrated among 6 U.S. centers, raising the possibility of expedited placement. Therefore, we evaluated all national offers of nationally placed livers (n=1625) to adult wait-list candidates from 2/05-1/10. We developed a model to predict national utilization pathways; pathways exceeding expected by ≥3 standard errors of the best-fit linear unbiased predictions were defined as "preferred". All 51 donation service areas (DSAs) placed ≥1 liver nationally, but the %/DSA ranged from 1-36%. Of 2830 possible national DSA→center pathways, 87% were utilized. 580(36%) livers were accepted on the first national offer. Four DSAs accounted for 47% of first national offer livers, of which 44% were accepted by a single center. Compared to first offer livers utilizing non-preferred pathways, first offers along a preferred pathway were offered to fewer Status 1 candidates (19 vs. 61%) and had lower median MELD scores (22 vs. 36) [p<0.001]. In conclusion, DSA placement patterns of national livers vary widely, with four DSAs exporting a high proportion of national livers on the first national offer to non-Status 1 candidates with MELD scores less than their local transplant MELD. While this practice may have facilitated liver placement, it raises the possibility of expedience trumping patient need. Here, we propose changes to the national liver distribution system that help balance equity, efficiency, and transparency. © 2013 American Association for the Study of Liver Diseases.
    Liver Transplantation 04/2013; 19(4). DOI:10.1002/lt.23604 · 3.79 Impact Factor
  • 01/2013; 15(11):966-972. DOI:10.1001/virtualmentor.2013.15.11.pfor2-1311
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    ABSTRACT: In the United States, the peak hepatitis C virus (HCV) antibody prevalence of 4% occurred in persons born in the calendar years 1940-1965. The goal of this study was to examine observed and projected age-specific trends in the demand for liver transplantation (LT) among patients with HCV-associated liver disease stratified by concurrent hepatocellular carcinoma (HCC). All new adult LT candidates registered with the Organ Procurement and Transplantation Network for LT between 1995 and 2010 were identified. Patients who had primary, secondary, or text field diagnoses of HCV with or without HCC were identified. There were 126,862 new primary registrants for LT, and 52,540 (41%) had HCV. The number of new registrants with HCV dramatically differed by the age at calendar year, and this suggested a birth cohort effect. When the candidates were stratified by birth year in 5-year intervals, the birth cohorts with the highest frequency of HCV were as follows (in decreasing order): 1951-1955, 1956-1960, 1946-1950, and 1941-1945. These 4 birth cohorts, spanning from 1941 to 1960, accounted for 81% of all new registrants with HCV. A 4-fold increase in new registrants with HCV and HCC occurred between the calendar years 2000 and 2010 in the 1941-1960 birth cohorts. By 2015, we anticipate that an increasing proportion of new registrants with HCV will have HCC and be ≥60 years old (born in or before 1955). In conclusion, the greatest demand for LT due to HCV-associated liver disease is occurring among individuals born between 1941 and 1960. This demand appears to be driven by the development of HCC in patients with HCV. During the coming decade, the projected increase in the demand for LT from an aging HCV-infected population will challenge the transplant community to reconsider current treatment paradigms. Liver Transpl, 2012. © 2012 AASLD.
    Liver Transplantation 12/2012; 18(12). DOI:10.1002/lt.23551 · 3.79 Impact Factor
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    ABSTRACT: During long-term follow-up, 18% to 67% of pediatric liver transplant recipients are overweight or obese, with rates varying by age and pretransplant weight status. A similar prevalence of posttransplant obesity has been seen in adults. Adults also develop posttransplant metabolic syndrome and, consequently, cardiovascular disease at rates that exceed the rates in age- and sex-matched populations. Posttransplant metabolic syndrome has never been studied in pediatric liver transplant recipients, and this population is growing as transplant outcomes continue to improve. Here we systematically review the literature for each component of metabolic syndrome-obesity, hypertension, dyslipidemia, and glucose intolerance-in pediatric liver transplant recipients. Their rates of obesity are similar to the rates in children in the general U.S. population. However, hypertension, dyslipidemia, and diabetes are more common than would be expected in transplant recipients according to age, sex, and obesity severity. Immunosuppressive medications are major contributors. The limitations of previous studies, including heterogeneous methods of diagnosis, follow-up times, and immunosuppressive regimens, hinder the analysis of risk factors. Importantly, no studies have reported graft or patient outcomes associated with components of metabolic syndrome after pediatric liver transplantation. However, if the trends in children are similar to the trends seen in adults, these conditions may lead to significant long-term morbidity. Further research on the prevalence, causes, and consequences of posttransplant metabolic syndrome in pediatric liver transplant recipients is needed and will ultimately help to improve long-term outcomes.
    Liver Transplantation 09/2012; 18(9):1009-28. DOI:10.1002/lt.23478 · 3.79 Impact Factor
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    ABSTRACT: Loco-regional therapy has been developed to reduce waitlist dropout in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation. We evaluated the probability of transplantation and waitlist dropout, and analyzed risk factors for waitlist dropout, in 76 patients with HCC from September 2004 to August 2006. Seventy-three (96.1%) patients received one or more preoperative loco-regional treatments and 55 (72.3%) received an orthotopic liver transplantation with a median wait time of seven months (range, 2-26 months). There were 11 dropouts (14.5%) associated with tumor progression or hepatic decompensation (median waiting time; 5.4 months and range, 0.4-13 months). Cumulative probabilities of transplantation at three, six, nine, 12, 15, and 18 months were 5.4%, 35.4%, 67.5%, 78.8%, 80.7%, and 80.7%, respectively and those of waitlist dropout at three, six, nine, 12, 15, and 18 months were 3.9%, 8.7%, 12.8%, 22.9%, 29.3%, and 29.3%, respectively. A laboratory model for end-stage liver disease (MELD) score >15 or multiple tumors at the time of UNOS listing were significant risk factors for waitlist dropout (p = 0.006 and 0.026, respectively). Patients with HCC being managed with loco-regional therapy who have a laboratory MELD score >15 or multiple tumors should be considered for earlier access to liver transplantation to prevent waitlist dropout.
    Clinical Transplantation 06/2012; 26(4):E359-64. DOI:10.1111/j.1399-0012.2012.01668.x · 1.49 Impact Factor
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    ABSTRACT: The demographics of patients in the United States who undergo living donor liver transplantation (LDLT) versus patients who undergo deceased donor liver transplantation (DDLT) are interesting with respect to the demographics of the donor service areas (DSAs). We examined adult recipients of primary, non-status 1 liver-only transplants from 2003 to 2009. The likelihood of undergoing LDLT was compared to the likelihood of undergoing DDLT by multivariate logistic regression. We examined the adjusted odds ratio (OR) for undergoing LDLT versus DDLT for patients with the same diagnosis and blood type after we stratified the DSAs into quintiles by the median match Model for End-Stage Liver Disease (MELD) scores. LDLT was performed for 1497 of 32,927 liver transplants (4.5%). LDLT decreased in frequency by approximately 30% from 2003 to 2009. In comparison with DDLT recipients, LDLT recipients were younger and had higher albumin levels, lower body mass indices, and lower match MELD scores. Females had increased odds of LDLT in comparison with males (OR = 1.74, P < 0.001). Patients with MELD exception scores were less likely to undergo LDLT (OR = 0.22, P < 0.001). Patients with cholestatic liver disease (adjusted OR = 2.04, P < 0.001) or malignant neoplasms other than hepatocellular carcinoma (adjusted OR = 3.33, P < 0.001) were more likely than patients with hepatitis C virus to undergo LDLT. Other characteristics associated with decreased odds of LDLT were black race (adjusted OR = 0.41, P < 0.001) and government insurance (adjusted OR = 0.51, P < 0.001). LDLT was more frequent in DSAs with high median MELD scores; the adjusted OR for LDLT was 38 for the DSAs in the highest quintile (P < 0.001). In conclusion, there are significant differences associated with race, insurance, sex, MELD exceptions, and DSA MELD scores between patients who undergo LDLT and patients who undergo DDLT. These differences can be hypothesized to be driven in part by the relative availability of LDLT versus DDLT at both the patient level and the DSA level.
    Liver Transplantation 02/2012; 18(2):160-5. DOI:10.1002/lt.22455 · 3.79 Impact Factor
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    ABSTRACT: Although life-saving, liver transplantation burdens children with lifelong immunosuppression and substantial potential for morbidity and mortality. To establish the feasibility of immunosuppression withdrawal in pediatric living donor liver transplant recipients. Prospective, multicenter, open-label, single-group pilot trial conducted in 20 stable pediatric recipients (11 male; 55%) of parental living donor liver transplants for diseases other than viral hepatitis or an autoimmune disease who underwent immunosuppression withdrawal. Their median age was 6.9 months (interquartile range [IQR], 5.5-9.1 months) at transplant and 8 years 6 months (IQR, 6 years 5 months to 10 years 9 months) at study enrollment. Additional entry requirements included stable allograft function while taking a single immunosuppressive drug and no evidence of acute or chronic rejection or significant fibrosis on liver biopsy. Gradual immunosuppression withdrawal over a minimum of 36 weeks was instituted at 1 of 3 transplant centers between June 5, 2006, and November 18, 2009. Recipients were followed up for a median of 32.9 months (IQR, 1.0-49.9 months). The primary end point was the proportion of operationally tolerant patients, defined as patients who remained off immunosuppression therapy for at least 1 year with normal graft function. Secondary clinical end points included the durability of operational tolerance, and the incidence, timing, severity, and reversibility of rejection. Of 20 pediatric patients, 12 (60%; 95% CI, 36.1%-80.9%) met the primary end point, maintaining normal allograft function for a median of 35.7 months (IQR, 28.1-39.7 months) after discontinuing immunosuppression therapy. Follow-up biopsies obtained more than 2 years after completing withdrawal showed no significant change compared with baseline biopsies. Eight patients did not meet the primary end point secondary to an exclusion criteria violation (n = 1), acute rejection (n = 2), or indeterminate rejection (n = 5). Seven patients were treated with increased or reinitiation of immunosuppression therapy; all returned to baseline allograft function. Patients with operational tolerance compared with patients without operational tolerance initiated immunosuppression withdrawal later after transplantation (median of 100.6 months [IQR, 71.8-123.5] vs 73.0 months [IQR, 57.6-74.9], respectively; P = .03), had less portal inflammation (91.7% [95% CI, 61.5%-99.8%] vs 42.9% [95% CI, 9.9%-81.6%] with no inflammation; P = .04), and had lower total C4d scores on the screening liver biopsy (median of 6.1 [IQR, 5.1-9.3] vs 12.5 [IQR, 9.3-16.8]; P = .03). In this pilot study, 60% of pediatric recipients of parental living donor liver transplants remained off immunosuppression therapy for at least 1 year with normal graft function and stable allograft histology.
    JAMA The Journal of the American Medical Association 01/2012; 307(3):283-93. DOI:10.1001/jama.2011.2014 · 30.39 Impact Factor

Publication Stats

7k Citations
973.72 Total Impact Points

Institutions

  • 2015
    • St. Elizabeth's Medical Center
      Boston, Massachusetts, United States
  • 1990–2015
    • University of California, San Francisco
      • • Division of Transplant Surgery
      • • Department of Surgery
      • • Division of Hospital Medicine
      San Francisco, California, United States
  • 2011
    • University of San Francisco
      San Francisco, California, United States
  • 2010
    • University of Nebraska Medical Center
      • Department of Surgery
      Omaha, Nebraska, United States
  • 2005
    • Chonnam National University
      • Department of Surgery
      Gwangju, Gwangju, South Korea
  • 2002
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
    • Philadelphia College of Osteopathic Medicine
      Philadelphia, Pennsylvania, United States
  • 1999
    • California Pacific Medical Center Research Institute
      • Department of Transplantation
      San Francisco, California, United States
  • 1996
    • University of California, Davis
      Davis, California, United States