Cohort Of Liver Transplant Recipients Research Articles

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9months, 3-9months and 4.5months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73m2 /month, P=0.03) independently of the pre-treatment eGFR (P=0.99), ribavirin administration (P=0.26), mycophenolate mofetil administration (P=0.51) and stage of fibrosis (F3 and F4 vs lower stages, P=0.18; F4 vs lower stages, P=0.08; F4 Child-Pugh B and C vs lower stages, P=0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P=0.34, 0.08, 0.73). The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

Subsequent nonmelanoma skin cancers and impact of immunosuppression in liver transplant recipients.

Nonmelanoma skin cancers (NMSCs) are the most frequent cancers in solid organ transplant recipients, with a high rate of subsequent tumors. To describe subsequent NMSCs in a large cohort of liver transplantrecipients (LTRs) with long follow-up and analyze the factors influencing it, including immunosuppressive regimen. A total of 96 LTRs (76 male) with a personal post-transplant history of squamous cell carcinoma, basal cell carcinoma or Bowen's disease were included, with a median follow-up of 12.4years (range, 1.5-27.8) after liver transplantation. The median follow-up after first NMSC was 6.4years (range, 0.17-22.1). In all, 52 patients (53.1%) developed 141 subsequent NMSCs with a basal cell carcinoma-to-squamous cell carcinoma ratio of 1.8:1. The actuarial risk for development of a second NMSC was 13.7% at 1year, 28.4% at 2years, 49.4% at 5years, 65.7% at 10years, and 88.4% at 15years. Multivariate analysis found that skin phototype I or II (vs III or IV) was a significant risk factor for development of a second NMSC (hazard ratio, 2.556; 95% confidence interval, 1.45-4.48; P=.001), whereas withdrawal of calcineurin inhibitors was significantly protective (hazard ratio, 0.358; 95% confidence interval, 0.142-0.902; P=.029). Retrospective analysis. Subsequent NMSCs are very frequent in LTRs, and conversion from a calcineurin inhibitor-based immunosuppressive regimen to a mammalian target of rapamycin inhibitor/antimetabolite-based immunosuppressive regimen can reduce subsequent NMSCs.

Pretransplant coronary artery disease is a predictor for myocardial infarction and cardiac death after liver transplantation

BackgroundCardiovascular disease is a serious problem of liver transplant (LT) recipients because of increased cardiovascular risk due to immunosuppressive therapy, higher age, intraoperative risk and comorbidities (such as diabetes and nicotine abuse). Reported frequency of cardiovascular events after LT shows a high variability between different LT cohorts. Our aim was to analyze a cohort of LT recipients from a single center in Germany to evaluate frequency of the cardiovascular endpoints (CVE) myocardial infarction and/or cardiac death after LT and to investigate correlations of CVE post LT with pretransplant patient characteristics. PatientsIn total, data from 352 LT patients were analyzed. Patients were identified from an administrative transplant database, and all data were retrieved from patients' charts and reports. ResultsDuring the median follow-up of 4.0 (0−13) years, 10 cases of CVE were documented (six myocardial infarctions and four coronary deaths). The frequency of CVE did not differ according to classic cardiovascular risk factors such as body mass index (p=0.071), total cholesterol (p=0.533), hypertension (p=0.747), smoking (p=1.000) and pretransplant diabetes mellitus (p=0.146). In patients with pretransplant coronary heart disease (n=24; 6.8%) CVE were found more frequently (p=0.024). ConclusionIn summary, we found a rate of 2.8% CVE after LT in a German transplant cohort. Pretransplant CHD was the only risk factor for CVE, but showed no significant impact on overall survival.

A2 liver transplantation across the ABO barrier: Increasing options in the donor pool?

A2 liver transplantation across the ABO barrier: Increasing options in the donor pool?

A Mutation in the Progesterone Receptor Is Associated to Hepatitis E Seroprevalence in Liver Transplant Recipients and Correlates With Altered Immune Markers in Serum: 2017 Presidential Poster Award

Introduction: Infection with the hepatitis E virus (HEV) can cause acute hepatitis in immunocompetent hosts as well as liver failure in pregnant women. Recent reports indicate that HEV can lead to chronic infection or acute reactivation in immunocompromised subjects, particularly transplant recipients. A recent study showed that a mutation in the progesterone receptor named PROGINS could confer a higher risk of fulminant hepatic failure by HEV in pregnant women. This mutation is thought to affect the host's immune response to HEV. We have recently shown that the PROGINS mutation is expressed with a higher frequency in individuals with the human immunodeficiency virus who are seropositive for HEV. In this study we studied the frequency of the PROGINS mutations in liver transplant recipients seropositive for HEV. Methods: We evaluated the presence of PROGINS in liver transplant recipients and its relation to HEV infection. Serum samples from 69 individuals who received a liver transplantation were analyzed for the presence of PROGINS through KASP assay. A group of 187 healthy samples were used as controls. Of the 69 transplant recipients, 46 were HEV IgG negative and 23 HEV IgG positive. In a subset of samples, multiplex cytokine assays were performed to compare levels among liver transplant recipients with and without the PROGINS mutation. Results: We found the frequency of PROGINS in transplant recipients HEV-positive to be 35%, compared to 15% in those that were HEV-negative (RR 2.2, CI 0.9-5.5). The frequency of the mutation in the HEV-negative group was similar to that in healthy controls (14%). When we compared serum levels of multiple immune markers among a subgroup of liver transplant recipients with HEV and the presence of PROGINS (N: 7 each group), we found reduced levels of MIG, APRIL and SCF, as well as increased levels of Eotaxin 3 and IL-31, when compared to liver transplant recipients negative for HEV with wild type progesterone receptor. Conclusion: Our results from a small cohort of liver transplant recipients show a strong trend towards an increased frequency of the PROGINS mutations among those that are seropositive for HEV. These patients expressed altered serum levels of multiple immune markers when compared to those without PROGINS. A study with a larger validation cohort is on the way to confirm this finding and examine its implications.

Surgical Site Infections After Liver Transplantation: Prospective Surveillance and Evaluation of 250 Transplant Recipients in Canada.

OBJECTIVE To evaluate the incidence of surgical-site infections (SSIs) in a cohort of liver transplant recipients and to assess risk factors predisposing patients to these infections. DESIGN Prospective observational cohort study. SETTING Single transplant center in Canada. PATIENTS Patients who underwent liver transplantation between February 2011 and August 2014. METHODS Multivariate logistic regression was used to identify independent risk factors for SSIs in liver transplant patients. RESULTS We enrolled 250 liver transplant recipients. The recipients' median age at the time of transplantation was 56 years (range, 19-70 years), and 166 patients (66.4%) were male. Moreover, 47 SSIs were documented in 43 patients (17.2%). Organ-space, superficial, and deep SSIs were noted in 29, 7, and 3 patients, respectively. In addition, 2 patients developed superficial and organ-space SSIs, and another 2 patients were found to have deep as well as organ-space infections. In total, we identified 33 organ-space SSIs (70.2%), 9 superficial SSIs (19.1%), and 5 deep SSIs (10.6%). Factors predictive of SSIs by multivariate analysis were duct-to-duct anastomosis (odds ratio [OR], 3.88; 95% CI, 1.85-8.13; P<.001) and dialysis (OR, 3.57; 95% CI, 1.02-12.50; P=.046). Of the 66 organisms isolated in both deep and organ-space SSIs, 55 (83%) were resistant to cefazolin. CONCLUSIONS Organ-space SSIs are a common complication after liver transplantation. Duct-to-duct anastomosis and dialysis were independent risk factors associated with SSIs. Appropriate perioperative prophylaxis targeting patients with duct-to-duct anastomosis and dialysis while simultaneously providing optimum coverage for the potential pathogens causing SSIs is warranted. Infect Control Hosp Epidemiol 2017;38:1084-1090.

Favorable longterm outcomes of liver transplant recipients treated de novo with once-daily tacrolimus: Results of a single-center cohort.

The once-daily prolonged-release formulation of tacrolimus has been recently related with significant graft and patient mid-term survival advantages; however, practical information on the de novo administration after liver transplantation and longterm outcomes is currently lacking. This study is a 5-year retrospective analysis of a single-center cohort of liver transplant recipients treated de novo with once-daily tacrolimus (April 2008/August 2011). The study cohort consisted of 160 patients, including 23 with pretransplant renal dysfunction, with a median follow-up of 57.6 months (interquartile range, 46.6-69.0). Tacrolimus target trough levels were 5-10 ng/mL during the first 3 months after transplant, reducing progressively to <7 ng/mL after the first posttransplant year. Once-daily tacrolimus was withdrawn in 35 (21.8%) patients during follow-up, mostly due to renal dysfunction and/or metabolic syndrome. The biopsy-proven acute rejection rate was 12.5% with no cases of steroid-resistant rejection. The cumulative incidence of de novo diabetes, hypertension, and dyslipidemia were 16.9%, 31.2%, and 6.5%, respectively. Hepatocellular carcinoma recurrence rate was 2.8%. Renal function remained stable after the sixth month after transplant with a mean estimated glomerular filtration rate of 77.7 ± 19.6 mL/minute/1.73 m(2) at 5 years. None of our patients developed chronic kidney disease stage 4 or 5. Patient survival at 1, 3, and 5 years was 96.3%, 91.9%, and 88.3%, respectively. Overall survival of patients with Model for End-Stage Liver Disease (MELD) score > 25 points was not significantly different. In conclusion, our study suggests that immunosuppression based on de novo once-daily tacrolimus is feasible in routine clinical practice, showing favorable outcomes and outstanding longterm survival even in patients with high MELD scores. Liver Transplantation 22 1391-1400 2016 AASLD.

ACUTE APENDICITIS IN LIVER TRANSPLANT RECIPIENTS.

Background : Appendicitis is a common cause of emergency surgery that in the population undergoing organ transplantation presents a rare incidence due to late diagnosis and treatment. Aim : To report the occurrence of acute appendicitis in a cohort of liver transplant recipients. Methods : Retrospective analysis in a period of 12 years among 925 liver transplants, in witch five cases of acute appendicitis were encountered. Results : Appendicitis occurred between three and 46 months after liver transplantation. The age ranged between 15 and 58 years. There were three men and two women. The clinical presentations varied, but not discordant from those found in non-transplanted patients. Pain was a symptom found in all patients, in two cases well located in the right iliac fossa (40%). Two patients had symptoms characteristic of peritoneal irritation (40%) and one patient had abdominal distention (20%). All patients were submitted to laparotomies. In 20% there were no complications. In 80% was performed appendectomy complicated by suppuration (40%) or perforation (40%). Superficial infection of the surgical site occurred in two patients, requiring clinical management. The hospital stay ranged from 48 h to 45 days. Conclusion : Acute appendicitis after liver transplantation is a rare event being associated with a high rate of drilling, due to delays in diagnosis and therapy, and an increase in hospital stay.

Osteoporosis in Liver Transplant Recipients: Defining Incidence and Risk Factors

Introduction: Osteoporosis is common disorder among patients with liver transplantation (LT). However, specific risk factors for bone disease in this population have not been fully elucidated. In general population, research has linked hypertension to osteoporosis, but data linking hypertension and osteoporosis in LT recipients is scarce. Studies have shown that in kidney transplant recipients, high levels of Tacrolimus (TAC) is associated with risk of bone loss, but data on association between use of TAC and bone disease in LT recipients is scarce. We aimed to define the incidence and risk factors associated with bone disease, among our LT recipients. Methods: We conducted a retrospective review of LT recipients from our prospective database with the ICD-9 code V42.7 for “liver replaced by transplant”. The study population included patients who had received LT at our institution between 2010 and 2013. We recorded recipients' DEXA scan findings, age, sex, height, weight, previous medical conditions, drug use, alcohol consumption, and medications. In addition, vitamin D levels, CBC, comprehensive metabolic panel, and lipid panel were recorded before and after LT and at last follow up. All data was recorded in Microsoft Excel and analyzed using mean and SD. Results: Of the 46 recipients identified, 24 had DEXA scans; sixteen (67%) had osteoporosis and 29% had osteopenia, only one had a normal study. The average age at diagnosis was 58 ± 9 years with a male to female ratio of 11:13. The average BMI was 28.0 ± 5.5 kg/m2. Hepatitis C was the most common etiology for transplant (78%). Eighteen (78%) had hypertension and 17 (74%) were diabetic. Seventeen patients (71%) had a history of tobacco use. All recipients (100%) had at least one of these three afore mentioned risk factors. The median vitamin D level was 25 ng/mL and 29 ng/mL in recipients with osteoporosis and osteopenia respectively (P=0.41). The mean corrected calcium level was 9.5 ± 0.79 mg/dL and 9.2 ± 0.75 mg/dL. Sixteen recipients (70%) were on Tacrolimus, which was the most common medication in this population. Conclusion: We had a high incidence of osteoporosis/osteopenia (96%) in our cohort of LT recipients. Bone disease is significant comorbidity in LT recipients. All recipients had either hypertension, diabetes, or a history of tobacco use, and 70% were on Tacrolimus. Prospective studies are required to better define the relation between these risk factors and bone disease in this unique population.

Cytomegalovirus: Why Viral Dynamics Matter

Contrary to bacterial replicating kinetics, where the doubling time varies considerably but often is measured in minutes or hours, viral replication kinetics is calculated in days. A new study by Isabelle Lodding and colleagues in E-Biomedicine attempts to calculate the doubling time of cytomegalovirus (CMV) in a cohort of solid organ and stem cell recipients (Lodding et al., 2015). Why does the doubling time of CMV matter? This number is of great interest to the transplant specialist, as the preemptive treatment approach relies on the detection of replicating CMV in blood before disease occurs. Regular determination of quantitative CMV PCR testing allows selecting those patients with reactivation of CMV in need of a preemptive treatment. Often, a quantitative CMV copy threshold in blood is used to start antiviral treatment. Neither the optimal frequency of CMV testing nor the ideal source of CMV PCR (whole blood, or plasma), nor the optimal threshold has been established. Thus, protocols between transplant centers vary. The recently published updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation recommended weekly testing for 3–4 months, with moderate evidence (Kotton et al., 2013). For most centers, however, it would be very difficult to adhere to such a tight schedule, in particular later after transplantation. Therefore, a precise knowledge of the doubling time would allow to safely widen the interval between CMV PCR testing, without an increase in CMV disease episodes. The main finding of the study by Lodding and colleagues is a CMV doubling time of 4.3 days (median, IQR 2.5–7.8), which in contrast to earlier studies is considerably longer. Neither the donor–recipient CMV sero-constellation nor the type of transplant did influence these results. Earlier studies by V. Emery and P. Griffiths in bone marrow transplant patients estimated a shorter doubling time of CMV of 1.5 days (median, range 0.38–4.7) (Emery et al., 1999). Similar doubling times were calculated in a cohort of liver transplant recipients (2 days (median, 0.1–69)) (Nebbia et al., 2007). Many factors may have influenced these different estimates, including the intensity of immunosuppression, the type of sample used for CMV PCR detection, frequency of measurement, type of transplantation, or percentage of patients at high risk for CMV reactivation. While some are less likely than other to play a role, data on the influence of these factors on the doubling time are conflicting. Interestingly, in their simulation model, Lodding and colleagues were able to predict their real rate of recipients with a high CMV viral load (1.4%, arbitrarily set at > 18,200 IU/mL) with the assumption of their lower doubling time of 4.3 days. Using a shorter doubling time of 1.3 days, the proportion of patient with a high viral load would have been 11%. The authors suggest that in cohorts with comparable doubling times, the screening interval can be safely extended. While this may decrease the cost burden due to less visits and screening costs, it should be emphasized that the most important goal is to reduce symptomatic CMV episodes in these vulnerable patients. We and others have shown that many factors including as strict adherence to a guideline with timely start of antiviral therapy in case of reactivation contribute to the success of the preemptive approach (Greiner et al., 2012). Of note, the number of patients with CMV disease was rather high and reached 31% during the observation time in the study by Lodding and colleagues. The basis of any informed decision on how to adapt the screening schedule is a precise knowledge of the rate of CMV disease episodes in its own institution. Such information is crucial to recognize a relevant increase in the rate of CMV disease once changes of the preemptive protocol have been implemented. Any change in clinical routine should be accompanied by a careful evaluation of its effect on the pertinent endpoints. The importance of the role of carefully maintained cohorts such as the one built and used to by Lodding and colleagues to answer such questions in a real-life environment cannot be overstated.

Delayed-onset cytomegalovirus disease coded during hospital readmission in a multicenter, retrospective cohort of liver transplant recipients.

Delayed-onset cytomegalovirus (CMV) disease can occur among liver transplant recipients after CMV prophylaxis is stopped. We hypothesized that delayed-onset CMV disease (>100 days after transplant) occurs more commonly than early-onset CMV disease and is associated with clinical sepsis and death. Using 2004-2010 International Classification of Diseases, Ninth Revision, Clinical Modification billing data from 4 Healthcare Cost and Utilization Project state inpatient databases, we assembled a large and more representative cohort of 7229 adult liver transplant recipients from 26 transplant centers, and we identified demographics, comorbidities, CMV disease, and clinical sepsis coded during readmission and inpatient death. Multivariate analysis was performed with Cox proportional hazards models. Delayed-onset CMV disease occurred in 4.3% (n = 309), whereas early-onset CMV disease occurred in 2% (n = 142). Delayed-onset CMV disease was associated with previous transplant failure or rejection [adjusted hazard ratio (aHR), 1.4; 95% confidence interval (CI), 1.1-1.7]. Clinical sepsis > 100 days after transplant was associated with previous CMV disease (aHR, 1.3; 95% CI; 1.0-1.7), previous transplant failure or rejection (aHR, 2.1; 95% CI; 1.8-2.4), female sex (aHR, 1.3; 95% CI; 1.1-1.5), and several comorbidities. Death > 100 days after transplant was associated with delayed-onset CMV disease (aHR, 2.0; 95% CI; 1.6-2.6), transplant failure or rejection (aHR, 4.3; 95% CI; 3.4-5.5), increasing age by decade (aHR, 1.1; 95% CI; 1.0-1.2), and some comorbidities. In conclusion, delayed-onset CMV disease is more common than early-onset CMV disease among liver transplant recipients. Previous CMV disease may be a risk factor for clinical sepsis > 100 days after transplant, and delayed-onset CMV disease may be a risk factor for death > 100 days after transplant.

Donation after cardiac death liver transplantation is associated with increased risk of end-stage renal disease.

Limited organ supply has led to greater use of liver allografts with higher donor risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is associated with acute kidney injury after liver transplantation; however, less is known about the association between donor quality and end-stage renal disease (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD. Model 1 included total DRI; model 2 included components of DRI, including DCD, as separate variables. Forty thousand four hundred and sixty-three liver transplant recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%) received DCD livers. During median follow-up of 3.93years, ESRD occurred in 2008 (5%) and death in 11075 (27%) subjects. There was a stepwise increase in ESRD risk with higher DRI (DRI ≥1.14 and <1.40: HR 1.17, P=0.06; DRI ≥1.40 and <1.72: HR 1.29, P=0.003; DRI ≥1.72: HR 1.39, P<0.001, compared with DRI <1.14). Adjusting for DRI components separately, DCD status was most strongly associated with ESRD (HR 1.40, P=0.008). Higher DRI is associated with ESRD after liver transplantation, driven in part by DCD status. Donor quality is an important predictor of long-term renal outcomes in liver transplant recipients.

The Migrated Liver Transplantation Candidate: Insight into Geographic Disparities in Liver Distribution

A minority of liver transplantation (LT) candidates pursue listing at multiple centers to achieve transplantation. The purpose of this study was to assess the characteristics and outcomes of the migrated LT candidates, that is, those who travel to secondary centers seeking LT. Single-center retrospective study from January 1, 2005 to January 1, 2013 at a tertiary care center within United Network for Organ Sharing Region 1. Adult recipients who were listed at the primary center of interest, but subsequently achieved transplantation at a secondary center (Massachusetts General Hospital [MGH]-migrated; n= 44) were compared with recipients who achieved LT at the primary center (MGH-transplanted; n= 279). The MGH-migrated recipients most frequently traveled to United Network for Organ Sharing Region 3 (70.5%), with a mean (±SD) distance traveled of 1,134 (±392) miles. The MGH-migrated patients, when compared with MGH-transplanted recipients, spent more time on the waitlist (907.6 ± 930.1 days vs 354.9 ± 533.2 days; p < 0.00001), were more likely to have cholestatic liver disease (22.7% vs 6.8%; p= 0.0006) and private insurance (80.0% vs 51.6%; p= 0.0005), but were less likely to have alcoholic liver disease (2.3% vs 18.6%; p= 0.006) and Model for End-Stage Liver Disease exception points (6.8% vs 50.9%; p < 0.00001). On multivariable analysis, candidates with private insurance who lacked both alcoholic liver disease and Model for End-Stage Liver Disease exception point listing were significantly associated with the odds of pursuing migration. Despite achieving LT, MGH-migrated patients had inferior 5-year patient survival rates (63% vs 80%; p= 0.03). A small and distinctive cohort of LT recipients pursue migration to achieve transplantation. Travel patterns of migrated LT recipients appear to reflect the ongoing geographic disparities in liver distribution and underscore the need for alterations in policy to allow for equitable distribution.

Liver Transplant Center Performance Profiling: 2005–2011 Reports of the Scientific Registry for Transplant Recipients

CONTEXT-Transplant center performance profiling provides important information for various concerned parties. Comparing a transplant center's performance against the performance of the best-in-class centers may help in understanding the performance thresholds for the underperforming centers. OBJECTIVES-(1) To identify and describe "Centers for Medicare and Medicaid Services (CMS)-red-flag" performers and the "best-in-class" performers and (2) to examine the relationships between a center's performance profile and outcomes such as 1-year observed mortality, 1-month observed mortality, 1-year risk-adjusted mortality, and volume. METHODS-The data for analysis was obtained from the published reports on the Scientific Registry for Transplant Recipients (SRTR) website for adult liver transplant programs compiled for the rolling 2 1/2-year cohorts of patients and included 7 cohorts of liver transplant recipients in the study from January through July 1, 2002, through December 31, 2010. We defined 4 performance profiles: CMS-red-flag, lower-than-expected, higher-than-expected, and best-in-class performers. RESULTS-The current SRTR methods classify approximately 7% of the adult liver centers as CMS-red-flag performers and 6% of the centers as best-in-class performers in every reported period. Neither of the low-volume centers (<30 liver transplants per 2 1/2-year cohort) was profiled as CMS-red-flag until the 2010 reporting period. The transplant center's profile was significantly associated with the 1-year and 1-month observed mortality rates in every reported cohort (P< .001). CONCLUSION-The CMS-red-flag profile can be characterized with the following: (1) the highest observed 1-year mortality, (2) the highest observed 1-month mortality, (3) a very large difference between the observed and adjusted mortality rates, and (4) the center volume greater than 30 liver transplants per 2 1/2-year cohort. The SRTR methods are not sensitive for performance profiling in the centers that perform fewer than 30 orthotopic liver transplants per 2 1/2-year cohort.

Postliver Transplantation Pulmonary Complications

We read the article by Levesque et al. (1) with great interest. We congratulate the authors for addressing this important issue in the critical care of liver transplant recipients. We have few queries regarding the study. Until date, to our knowledge, this is the first study in cohort of liver transplant recipients using modified clinical pulmonary infection score (CPIS) to diagnose pneumonia. CPIS has been originally devised for diagnosis of ventilator-associated pneumonia (VAP) (2), and the authors did not mention the incidence of VAP. The authors used the modified CPIS score to confirm the diagnosis of pneumonia, which excludes the culture results (3). CPIS is still not validated for the diagnosis of VAP and has low sensitivity, 60%, and specificity, 43%, if it excludes the culture results (4). It would be great to know the sensitivity and specificity of CPIS score in this cohort as compared with quantitative bronchoalveolar lavage culture. In this study, there were 55 episodes of pneumonia; out of that, only 39 are reported to be culture positive. It means that, for 16 times, no microorganism was isolated. The protocol for antibiotics is for 48 hr after transplantation; how many patients were on antibiotics when they were diagnosed to have pneumonia? History of acute cellular rejection is an independent risk factor for developing pneumonia (5). The incidence of rejection in the study population is not mentioned. It will be interesting to know the risk of pneumonia in this subset of patients. In the pulmonary complication group, how many patients were having associated renal dysfunction that required dialysis? It might affect pulmonary complications (5). Did the authors control the ascites and pleural effusion before performing the pulmonary function test because it might improve patient compliance? At one point, it is stated that age is not the risk factor, but is the P value significant? Patients with upper abdominal surgery are expected to have some pleural effusion during the immediate postoperative period; however, in this study, pleural effusion was evaluated on the seventh day after the transplantation on computed tomographic scan as per routine protocol. Are there any other methods (bedside chest x-ray and ultrasound) used to evaluate pleural effusion before 7 days? How many patients experienced early effusion? Shridhar V. Sasturkar 1 Viniyendra Pamecha1 Vijay Kant Pandey2 1 Department of Hepatico-Pancreatic-Biliary Surgery and Liver Transplantation Institute of Liver and Biliary Sciences New Delhi, India 2 Department of Anesthesiology and Intensive Care Institute of Liver and Biliary Sciences New Delhi, India

Impact of Model for End-Stage Liver Disease in the Occurrence of Infectious Events and Survival in a Cohort of Liver Transplant Recipients

The Model for End-Stage Liver Disease (MELD), which predicts mortality on the waiting list before liver transplantation, has changed organ allocation criteria to prioritize severely ill patients. The aim of this study was to investigate the impact of the new criteria on the incidence of Healthcare Associated Infections (HAI) and patient survival after liver transplantation. This retrospective cohort included liver transplant recipients from 2005 to 2007. Infection notification followed the recommended criteria of the National Healthcare Safety Network (NHSN). Statistical analysis was performed using the Statistical Package for the Social Sciences. Of 142 patients, 67 (47.2%) underwent transplantation before June 2006. There were no differences between the 2 periods considering patient gender, diagnosis, age, length of hospitalization, and mean time to first infection occurrence. However, the length of intensive care unit (ICU) hospitalization (P = .006) and central venous catheter (CVC) use (P = .025) were higher in the first period of the study. Comparison of time until first systemic infection before and after changes in allocation criteria showed no significant difference (log-rank = 0.06; P = .81). There was a trend toward greater lethality during the second period of the study (P = .09). There was no difference in time to death between the 2 periods (log-rank = 0.9; P = .76). However, when comparing time to death of all patients with systemic infection versus those without this event, patients without infection showed a higher mortality rate (log-rank = 15.7; P < .001).

Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

Michael R. Lucey, Norah Terrault, Lolu Ojo, J. Eileen Hay, James Neuberger, Emily Blumberg, and Lewis W. Teperman Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI; Gastroenterology Division, Department of Medicine, University of California San Francisco, San Francisco, CA; Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI; Mayo Clinic, Rochester, MN; Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA; and Department of Surgery, NYU Transplant Associates, New York, NY

Obesity is an independent risk factor for pre-transplant portal vein thrombosis in liver recipients

BackgroundPortal vein thrombosis is a frequent complication in end-stage cirrhosis with a considerable peri-operative risk for liver transplant candidates. We aimed to characterize the pre-transplant portal vein thrombosis in a cohort of liver transplant recipients, and to identify independent risk factors for this complication.Methods380 consecutive primary orthotopic liver transplants were performed in the Digestive Surgery Department of “12 de Octubre” Hospital (Madrid, Spain), between January 2001 and December 2006. The main risk factors considered were smoking, obesity, metabolic disorders, previous immobility, surgery or trauma, nephrotic syndrome, associated tumor, inflammatory disease, neoplasm myeloprolipherative. Furthermore we have reported genetic thrombophilia results for 271 recipients.ResultsSixty-two (16.3%) patients developed pre-transplant portal vein thrombosis and its presence had no impact in the overall survival of liver recipients. Obesity was the only independent risk factor for pre-transplant portal vein thrombosis.ConclusionWe recommend close control of cardiovascular factors in patients with liver cirrhosis in order to avoid associated thrombosis.

Prevention of de novo hepatitis B with adefovir dipivoxil in recipients of liver grafts from hepatitis B core antibody-positive donors

Lamivudine has been shown to prevent de novo hepatitis B virus (HBV) infections in liver transplantation (LT) patients receiving hepatitis B core antibody-positive (HBcAb(+)) grafts, but it may produce long-term resistance. Adefovir dipivoxil (ADV) might be effective in preventing de novo hepatitis and resistance. A single-center, prospective trial was conducted with 16 adults (10 men and 6 women, mean age = 54 ± 11 years) who underwent LT with HBcAb(+) grafts between September 2007 and October 2009. After LT, patients were given ADV [10 mg daily (adjusted for renal function)]. No hepatitis B immune globulin was administered. At LT, all graft recipients were hepatitis B surface antigen-negative (HBsAg(-)), 38% were surface antibody-positive (HBsAb(+)), and 50% were HBcAb(+). The median follow-up after LT was 1.8 years (range = 1.0-2.6 years). All recipients had undetectable HBV DNA (<40 IU/mL) after LT until the end of follow-up. One recipient (6%) who was HBsAb(-) and HBcAb(-) before LT became HBsAg(+) after 52 weeks. One recipient was switched from ADV to entecavir for chronic renal insufficiency, and 19% of the patients had renal dose adjustments. There was a nonsignificant trend of increasing creatinine levels over time (1.2 mg/dL at LT, 1.3 mg/dL 1 year after LT, and 2.0 mg/dL 2 years after LT, P = 0.27). A comparison with a control cohort of LT recipients with hepatitis C virus who did not receive ADV showed no difference in the creatinine levels at LT or 1 year after LT. In conclusion, ADV prophylaxis prevents HBV replication in recipients of HBcAb(+) livers but does not fully protect recipients from de novo HBV. Long-term follow-up is needed to better determine the risk of de novo infection.

Recipient and donor thrombophilia and the risk of portal venous thrombosis and hepatic artery thrombosis in liver recipients

BackgroundVascular complications, such as HAT, are an important cause of graft loss and recipient mortality. We aimed to characterize post-transplant thrombotic events in a cohort of liver transplant recipients, and identify independent risk factors for these complications.MethodsWe conducted a thrombophilic study of 293 orthotopic liver transplants performed in the Digestive Surgery Department of the 12 de Octubre Hospital (Madrid, Spain) between January 2001 and December 2006.ResultsThe most frequent post-transplant thrombotic events were HAT (9%) and PVT (1.7%). The one variable associated with post-transplant thrombotic event was a high fibrinogen level in the global cohort of liver transplantation. But toxicity as event post-OLT has been associated with post-transplant thrombotic event in the retrospective group and high fibrinogen level and low protein C levels were associated post-transplant thrombotic event in the prospective group. Liver disease relapse (HR 6.609, p < 0.001), high levels of FVIII (HR 1.008, p = 0.019)) and low levels of antithrombin (HR 0.946, p < 0.001) were associated with poor overall survival (OS).In conclusion, high fibrinogen and decreased protein C levels were associated with allograft thrombosis. Further studies are required in order to assess the clinical relevance of these parameters in prospective studies and to study the effect of anticoagulation prophylaxis in this group of risk.