Months Of Liver Transplantation Research Articles

Immune Checkpoint Inhibitors Before Liver Transplantation May Increase the Risk of Rejection: A Meta-Analysis

Abstract Background Immune checkpoint inhibitors (ICI) represent a major breakthrough in cancer immunotherapy. Several molecules have shown efficacy in HCC and are increasingly used as a bridging therapy before liver transplantation. Initial reports have raised concern about severe rejections in patients following ICI therapy. Aims This meta-analysis assesses the risk of neoadjuvant ICI therapy before liver transplantation. Methods We systematically searched MEDLINE, Web of Science and Embase for studies including all patients treated with ICI therapy before liver transplantation from a given center. A random-effects model was applied to pooled results with a priori determined subgroup analyses. Results Eight studies published during the past three years fulfilled all inclusion criteria. All studies are noncomparative case series, one prospective, and seven retrospective. Studies included 52 patients who received various PD1 inhibitors between 1 and 253 days prior to liver transplantation. Patients treated with an ICI ahead of transplantation demonstrated an overall relative risk (RR) of 2.5 [95% CI: 1.4-3.8] for an acute rejection event. Furthermore, a subgroup analysis showed that patients who received PD1 inhibitors up to 30 days (RR 7.2 [95% CI: 4.9-10.5]) or between 30 and 60 days (RR 7.2 [95% CI: 5.1-10.3]) prior to liver transplantation suffered a higher rejection risk than patients with a “washout period” beyond 60 days (RR 1.8 [95% CI: 0.6-4.9]). The ICI, age, and underlying etiology were insignificant for RR in their subgroup analysis. Conclusion PD1 inhibitors within two months of liver transplantation may significantly elevate rejection risk. This meta-analysis provides valuable insights to inform clinical decision-making. Nevertheless, future trials remain imperative to establish definitive guidelines.

Association of physiological reserve measures with adverse outcomes following liver transplantation.

Background and AimThe comparative utility of physiological reserve measures in predicting important clinical outcomes following liver transplantation (LT) requires further study. The aim of this work was therefore to compare the utility of physiological reserve measures in predicting early adverse clinical outcomes post‐LT.MethodsA single‐center, retrospective cohort study of LT patients consecutively recruited between 1 January 2015, and 31 August 2020. Outcomes measured were sepsis and death within 12 months of LT, hospital length of stay (LOS), and intensive care LOS. Physiological reserve measures were handgrip strength, mid‐arm muscle circumference, and cardiopulmonary exercise testing (CPET) measures. Analysis was performed using univariate and multivariate logistic regression for sepsis and death, and univariate and multivariate Cox regression for hospital and intensive care LOS.ResultsData were obtained for 109 subjects. Patients were predominantly (64%) male with a median (interquartile range [IQR]) age of 57 (49–63) and median (IQR) Model for End‐Stage Liver Disease score of 16 (11–21). In multivariate analysis, the odds of sepsis were lower in patients in the highest versus lowest tertile (odds ratio = 0.004; 95% confidence interval [CI] 0.00–0.13; P = 0.002). Hospital LOS was linearly associated with handgrip strength (hazard ratio [HR] = 1.03; 95% CI 1.00–1.06; P = 0.03) in multivariate analysis. Intensive care LOS was associated with peak VO2 (HR 1.83; 95% CI 1.06–3.16; P = 0.03) and VE/VCO2 slope (HR 0.71; 95% CI 0.58–0.88; P = 0.002) in multivariate analysis.ConclusionHandgrip strength and CPET both identify candidates at high risk of adverse outcomes after LT.

Evaluation of ventricular systolic function by speckle tracking technique in patients with biliary atresia before and after liver transplantation

To evaluate the ventricular function of patients with biliary atresia (BA) before and after liver transplantation using two-dimensional speckle tracking. Observational, analytical study with healthy control group, volunteers. We recruited patients from 0 to 18 years old who were candidates for liver transplantation and patients after six months of liver transplantation performed for BA from January 1997 to August 2015 at Children’s Institute of São Paulo University Medical School. The patients were submitted to a complete conventional echocardiographic study. After that, the images were captured for global longitudinal strain (GLS). A blood sample was collected for brain natriuretic peptide (BNP) level. Ejection fraction obtained by Simpson’s method was significantly higher in the hepatic pre-transplantation group (p < 0.001), as well as left atrial size (p < 0.001) and left ventricle size (p = 0.039). The left ventricular mass index was significantly higher in pre-transplantation group (p < 0.001). The left atrium volume (p = 0.008) and the left ventricular mass index (p t = 0.035) were higher in the post-transplant group. It was observed that the lower the BNP, the lower/more negative the GLS in the post-transplant group (p = 0.038 and r = 0.427). Significant reduction in the overall longitudinal strain of the left ventricle was detected before (p = 0.01) and after liver transplantation (p = 0.019). A subclinical left ventricular systolic dysfunction was evidenced by two-dimensional speckle tracking technique before and after liver transplantation, even when compared to normal values of the last pediatric meta-analysis.

Post-operative assessment in patients after liver transplantation: imaging parameters associated with 1-year graft failure.

To identify post-liver transplant CT findings which predict graft failure within 1 year. We evaluated the CT scans of 202 adult liver transplants performed in our institution who underwent CT within 3 months after transplantation. We recorded CT findings of liver perfusion defect (LPD), parenchymal homogeneity, and the diameters and attenuations of the hepatic vessels. Findings were correlated to 1-year graft failure, and interobserver variability was assessed. Forty-one (20.3%) of the 202 liver grafts failed within 1 year. Graft failure was highly associated with LPD (n = 18/25, or 67%, versus 15/98, or 15%, p < 0.001), parenchymal hypoattenuation (n = 20/41, or 48.8% versus 17/161, or 10.6%, p < 0.001), and smaller diameter of portal veins (right portal vein [RPV], 10.7 ± 2.7 mm versus 14.7 ± 2.2 mm, and left portal vein [LPV], 9.8 ± 3.0 mm versus 12.4 ± 2.2 mm, p < 0.001, respectively). Of these findings, LPD (hazard ratio [HR], 5.43, p < 0.001) and small portal vein diameters (HR, RPV, 3.33, p < 0.001, and LPV, 3.13, p < 0.05) independently predicted graft failure. All the measurements showed fair to moderate interobserver agreement (0.233~0.597). For patients who have CT scan within the first 3 months of liver transplantation, findings of LPD and small portal vein diameters predict 1-year graft failure. •Failed grafts are highly associated with liver perfusion defect, hypoattenuation, and small portal vein. •Right portal vein < 11.5 mm and left portal vein < 10.0 mm were associated with poor graft outcome. •Liver perfusion defect and small portal vein diameter independently predicted graft failure.

Effects of tacrolimus (FK506) and mycophenolate mofetil (MMF) on regulatory T cells and co-inhibitory receptors in the peripheral blood of human liver allograft patients

Context: Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (FK506) may be an option for organ transplantation patients.Objective: In this study, we detected the effects of FK506 and MMF on the expressions of regulatory T cells (Tregs) and co-inhibitory receptors on Tregs in peripheral blood mononuclear cells (PBMC) of patients with stable phase after liver transplantation.Materials and methods: A total of 35 patients with stable stage after 6 months of liver transplantation were divided into two groups including 20 patients were treated with FK506 monotherapy (FK506 group), and 15 patients with FK506 and MMF combination (FK506 + MMF group). 15 healthy subjects were served as the control.Results: It is found that percentages of CD3+, CD3+CD4+ and CD3+CD8+ T cells in FK506 group are lowered compared to the control group but they are elevated in FK506 + MMF group. Amount of CD4+CD25+CD127low/-Treg cells in CD3+ CD4+T cells in FK506 + MMF group was higher than that in FK506 group and control group. The expressions of co-inhibitory receptors (CTLA-4, PD-1, Tim-3, LAG-3 and TIGIT) on Tregs in FK506 + MMF group were significant higher than those in the FK506 group and control group. The levels of the relative cytokines (TGF-β and IL-10) in FK506 group are down-regulated compared to the control group.Conclusion: The application of FK506 combined with MMF may be superior to FK506 monotherapy for the patients to further induce the immune tolerance after liver transplantation.

Nutritional Status of Liver Transplantation Recipients and Factors Influencing Nutritional Status

This study aimed to investigate the nutritional status of liver transplantation (LT) recipients and explore certain factors that influence nutritional status, including dietary patterns and physical activities. This was a cross-sectional, descriptive study. The subjects included 211 LT recipients at a medical center outpatient clinic located in Seoul, Korea. The nutritional status, dietary patterns, and physical activities of each subject were measured using the body mass index (BMI), Mini Dietary Assessment (MDA), and Global Physical Activity Questionnaire. Independent t-test, one-way analysis of variance, and multiple linear regression analysis were used to analyze the data. The percentages of living and deceased donor LTs were 81.0% and 19.0%, respectively. The mean BMIs pre- and post-LT were 23.88 and 23.16 kg/m², respectively, and the average MDA score was 36.55. More than 60.0% of the subjects had a moderate or high level of physical activity. In multivariate analysis, a higher BMI before LT (β=.72, p<.001), a lower Model for End-stage Liver Disease (MELD) score (β=-.18, p<.001), and being male (β=-.10, p=.024) contributed to better nutritional status post-LT. Patients within six months of LT were less engaged in muscle exercises than those post six months of LT (p=.020). LT recipients in Korea have good nutritional status and a good level of physical activity. To improve recipients' post-LT nutritional status, the pre-LT nutritional status should be considered, particularly in those with a higher MELD score. In addition, physical activity including muscle-strengthening exercises should be encouraged from an earlier stage.

Factors Associated With Recurrence of Primary Biliary Cholangitis After Liver Transplantation and Effects on Graft and Patient Survival

Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated riskfactors associated with recurrence of PBC and its effects onpatient and graft survival in a multicenter, international cohort (the Global PBC Study Group). We collected demographic and clinical data from 785 patients (89% female)with PBC who underwent liver transplantation (mean age, 54 ± 9 years) from February 1983 through June 2016, among 13 centers in North America and Europe. Results frombiochemical tests performed within 12 months of liver transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC(based on histologic analysis). Patients were followed for amedian 6.9 years (interquartile range, 6.1-7.9 years). PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years (HR, 1.39; 95% CI, 1.02-1.90; P= .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72-3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin ≥100 μmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P= .008) were associated with higher risk of PBCrecurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P= .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P= .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P= .02). Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects.

Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation.

Causes of severe cholestasis after liver transplantation (LT) are multi-factorial. Although the etiology is predictable in some, others culminate in graft/patient loss without a definitive cause identified. Severe cholestasis is usually associated with overlapped histological findings of rejection and biliary features, and diagnostic interpretation may pose a challenge. This is 10-year retrospective analysis of patients with unexplained severe cholestasis resulting in death/graft loss within 90 days of LT. Of 1 583 LT during the study period, 90-day graft failure occurred in 129 (8%) cases; a total of 45 (3%) patients had unresolving severe cholestasis (bilirubin, >100 μmol/L; alkaline phosphatase, >400 UI/L after 15 days from LT), excluding those due to primary nonfunction/sepsis/vascular causes (n = 84). Demographics, allograft biopsies, radiological investigations, and clinical outcome were analyzed. All patients had persistent abnormal liver biochemistry. Doppler ultrasound scan was normal in all cases. Thirty-five (78%) recipients had at least 1 allograft biopsy (2 [1-9]). On the first biopsy, 22 (63%) patients had acute rejection, 4 (18%) early-chronic rejection, 12 (34%) antibody-mediated rejection. In subsequent biopsies chronic rejection was evident in 5 (14%) cases. Donor-specific antibodies were detected in all patients tested. Biliary anatomy was studied in detail in 9 (20%) patients, all presenting biliary strictures. The majority (n = 39; 87%) died within 32 (10-91) days, only survivors were from retransplantation (n = 3;6.5%) and biliary intervention (n = 3;6.5%). Unresolving severe cholestasis after LT is a key parameter predicting patient/allograft outcome. Histologically, rejection seems to overlap with biliary strictures; hence, allograft biopsy with signs of rejection should not be a reason to overlook biliary problems, in particular when biliary features are present. Only extensive radiological investigation/intervention or retransplantation prevents patient/allograft loss.

Changes in dietary patterns and body composition within 12 months of liver transplantation.

Cardiometabolic risk factors are increasing in liver transplant recipients (LTR). Influencing dietary factors have not been assessed. The aim of this observational study was to assess changes in weight, metabolic function, dietary intake and eating behaviours in the first year after orthotopic liver transplantation (OLT). Consecutive recruitment of 17 patients (14 males) awaiting OLT at a single tertiary hospital. Dietary intake, food behaviours and anthropometry were recorded at baseline, and 6 and 12 months post-transplant. By 12 months, patients had gained on average 7.3% of body weight. The prevalence of overweight or obesity increased from baseline 53% to 77% (P=0.001). By 6 months, 65% (n=11/17) of patients had altered glucose metabolism. Dietary intake was consistent with a Western-style dietary pattern with high saturated fat. Over half of the patients (69%, n=11/16) reported low to no depressive feelings and rated their self-esteem as good (53%, n=9/16). The Power of Food Scale increased between pre and post-transplant, indicating a stronger appetitive drive. Weight gain occurs early post-transplant, with significant metabolic dysfunction present within 6 months, however is not associated with significant psychological distress. Early dietary intervention designed to limit weight gain and target cardiometabolic health is recommended for this unique patient population.

National assessment of early hospitalization after liver transplantation: Risk factors and association with patient survival.

Hospitalization is known to occur frequently in the first 6 months following liver transplantation (LT). Using a novel data linkage between the Scientific Registry of Transplant Recipients and Centers for Medicare and Medicaid Services, our study has 2 objectives: (1) to determine risk factors for "early" hospitalization (ie, within 6 months of LT); and (2) to quantify the importance of hospitalization history in the first 6 months with respect to subsequent patient survival (ie, survival, conditional on surviving 6 months post-LT). The study population consisted of patients aged ≥18 years who underwent deceased donor LT between January 1, 2003 and December 31, 2010, with Medicare as primary or secondary insurance and were discharged alive from the index LT hospitalization (n = 7220). The early hospitalization rate was 2.76 per patient-year and was significantly associated with many recipient factors (eg, recipient age, hepatitis C, diabetes, poor renal function including dialysis, and recipient of transjugular intrahepatic portosystemic shunt procedure before LT), as well as donor race and donation after cardiac death. Conditional on surviving 6 months after LT, the covariate-adjusted death rate increased by 22% for each additional hospitalization occurring in the first 6 months (hazard ratio, 1.22; P < 0.001). In conclusion, several LT recipient factors are significantly associated with early hospitalization. Moreover, a patient's hospitalization profile during follow-up months 0-6 is a very strong predictor of survival thereafter. Efforts and resources should be devoted toward identifying LT recipients at risk for early hospitalization and modifying the actionable risk factors such as hepatitis C, diabetes, and body mass index to improve resource utilization and overall outcomes. Liver Transplantation 23 1143-1152 2017 AASLD.

Pre-Liver Transplant Transthoracic Echocardiogram Findings and 6-Month Post-Transplant Outcomes: A Case-Control Analysis.

BACKGROUND Cardiopulmonary (CP) outcomes remain a leading cause of morbidity and mortality following liver transplantation (LT). The optimal CP risk stratification of LT candidates remains unclear. The aim of this study was to evaluate the association of pre-LT transthoracic echocardiogram (TTE) findings and 6-month post-LT outcomes. MATERIAL AND METHODS This retrospective review analyzed adults who underwent LT, comparing those who died within 6 months of LT (cases; n=38) with age- and sex-matched patients who survived >6 months (controls; n=38). Cases were categorized by cause of death (COD) defined as either a primary CP process (n=20) or a non-CP process (n=18). Data were analyzed using logistic regression and survival analysis was performed using Kaplan-Meier curves. RESULTS There was a higher odds of death within 6 months of LT with ≥ mild mitral regurgitation (OR 3.44, p=0.03) or an incomplete assessment of right ventricular systolic function (RVSF) (OR 24, p=0.004). On subgroup analysis, these findings only persisted in patients with a CP COD. Patients with CP COD were older (61 vs. 54.5, p=0.04), had longer intervals between TTE and LT (122 vs. 29 days, p=0.05), less complete assessments of RVSF (p=0.009), and lower RV fractional area change (p=0.04) compared to patients with non-CP COD. CONCLUSIONS Multiple TTE parameters were associated with patients who died within 6 months of LT, and in particular patients with a CP COD. Our findings suggest that pre-LT TTEs can convey useful CP risk stratification information and emphasizes the importance of adequately assessing these parameters prior to LT.

First-Degree Living-Related Donor Liver Transplantation in Autoimmune Liver Diseases.

Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.

Outcomes of pregnancy following liver transplantation: The King's College Hospital experience.

Reports of pregnancy in liver transplantation (LT) patients have largely favorable outcomes. Concerns remain with regards to maternal and graft risk, optimal immunosuppression (IS), and fetal outcomes. We review all post-LT pregnancies at our center with regard to the outcomes and safety for the patient, graft, and fetus. A total of 117 conceptions occurred in 79 patients. Median age at conception was 29 years. Maternal complications included graft loss (2%), acute cellular rejection (ACR; 15%), pre-eclampsia/eclampsia (15%), gestational diabetes (7%), and bacterial sepsis (5%). ACR was significantly more common in those women who conceived within 12 months of LT (P = 0.001). The live birth rate was 73%. Prematurity occurred in 26 (31%) neonates, and 24 (29%) neonates were of low or very low birth weight. IS choice (cyclosporine versus tacrolimus) had no significant effect on pregnancy outcomes and complications. No congenital abnormalities occurred, and only 1 child born at 24 weeks had delayed developmental milestones. In conclusion, pregnancy following LT has a favorable outcome in the majority, but severe maternal risks remain. Patients should be counseled with regard to the above information so informed decisions can be made, and pregnancy must be considered high risk with regular monitoring by transplant clinicians and specialist obstetricians.

Perioperative changes of procalcitonin levels in patients undergoing liver transplantation.

Severe sepsis is a life-threatening complication after liver transplantation (LT) that can be difficult to diagnose and appropriately treat after LT because of patients being treated with immunosuppressants. The present study examines perioperative changes in serum procalcitonin (PCT), a specific marker of systemic bacterial infection, and determines the value of PCT as a diagnostic tool for bacteremia or rejection. Perioperative serum PCT levels were prospectively assessed in 104 consecutive adult patients undergoing LT (living-donor LT, n = 90; deceased-donor LT, n = 14) between May 2010 and August 2012. Serum PCT levels remarkably increased soon after LT and gradually decreased thereafter, but were not increased in patients diagnosed with cytomegalovirus infection or acute cellular rejection. Serum PCT levels in patients who underwent deceased-donor LT were significantly higher than in those who underwent living-donor LT until postoperative day (POD) 7. Serum PCT levels were significantly higher in patients with bacteremia than in those without bacteremia after POD 14. In patients with post-transplant bacteremia, PCT levels increased again after POD 7 in patients who died within 3 months of LT, while levels remained low after POD 7 in patients who were alive. A positive predictive value of 83.3% for bacteremia and a negative predictive value of 97.4% were obtained at PCT cutoffs of 2.0 and 0.5 ng/mL, respectively. Serum PCT measurement, using appropriate cutoff values, could help diagnose severe infection, and might be able to differentiate bacteremia from acute cellular rejection.

Significance of Perioperative Procalcitonin Measurement in Patients Undergoing Liver Transplantation.

Severe sepsis is a life-threatening complication after liver transplantation (LT) that can be difficult to diagnose and appropriately treat after LT due to patients being administered with immunosuppressants. The present study examines perioperative changes in serum procalcitonin (PCT), a specific marker of systemic bacterial infection, and determines the value of PCT as a diagnostic tool for bacteremia or rejection. Perioperative serum PCT levels were prospectively assessed in 104 adult patients undergoing LT (living donor LT, n = 90; deceased donor LT, n = 14) between May 2010 and August 2012. Serum PCT levels remarkably increased soon after LT and gradually decreased thereafter, but were not increased in patients diagnosed with cytomegalovirus infection or acute cellular rejection. Serum PCT levels in patients who underwent deceased donor LT were significantly higher than those who underwent living donor LT until postoperative day (POD) 7. However, no differences were found between these two groups after POD 14. Serum PCT levels were significantly higher in patients with bacteremia than those without bacteremia after POD 5. PCT levels in patients with bacteremia who died within three months of LT and in patients who survived increased again and remained low, respectively after POD 7. A positive predictive value of 83.3% for bacteremia and a negative predictive value of 97.4% were obtained at PCT cut-offs of 2.0 and 0.5 ng/mL, respectively.In conclusions, perioperative PCT measurement would be useful to predict the prognosis of patients and differentiate bacteremia from rejection after LT.

Short-Term Pretransplant Renal Replacement Therapy and Renal Nonrecovery after Liver Transplantation Alone

Candidates with AKI including hepatorenal syndrome often recover renal function after successful liver transplantation (LT). This study examined the incidence and risk factors associated with renal nonrecovery within 6 months of LT alone among those receiving acute renal replacement therapy (RRT) before LT. Scientific Registry of Transplant Recipients data were linked with Centers for Medicare and Medicaid Services ESRD data for 2112 adult deceased-donor LT-alone recipients who received acute RRT for ≤90 days before LT (February 28, 2002 to August 31, 2010). Primary outcome was renal nonrecovery (post-LT ESRD), defined as transition to chronic dialysis or waitlisting or receipt of kidney transplant within 6 months of LT. Cumulative incidence of renal nonrecovery was calculated using competing risk analysis. Cox regression identified recipient and donor predictors of renal nonrecovery. The cumulative incidence of renal nonrecovery after LT alone among those receiving the pre-LT acute RRT was 8.9%. Adjusted renal nonrecovery risk increased by 3.6% per day of pre-LT RRT (P<0.001). Age at LT per 5 years (P=0.02), previous-LT (P=0.01), and pre-LT diabetes (P<0.001) were significant risk factors of renal nonrecovery. Twenty-one percent of recipients died within 6 months of LT. Duration of pretransplant RRT did not predict 6-month post-transplant mortality. Among recipients on acute RRT before LT who survived after LT alone, the majority recovered their renal function within 6 months of LT. Longer pre-LT RRT duration, advanced age, diabetes, and re-LT were significantly associated with increased risk of renal nonrecovery.

Equivalent survival following liver transplantation in patients with non-alcoholic steatohepatitis compared with patients with other liver diseases

BackgroundOrthotopic liver transplantation (LT) in non-alcoholic steatohepatitis (NASH) is increasing in parallel with the obesity epidemic. MethodsThis study retrospectively reviewed the clinical outcomes of LTs in NASH (n= 129) and non-NASH (n= 775) aetiologies carried out at a single centre between 1999 and 2009. ResultsRates of 1-, 3- and 5-year overall survival in NASH (90%, 88% and 85%, respectively) were comparable with those in non-NASH (92%, 86% and 80%, respectively) patients. Mortality within 4 months of LT was twice as high in NASH as in non-NASH patients (8.5% vs. 4.2%; P= 0.04). Compared with non-NASH patients, post-LT mortality in NASH patients was more commonly caused by infectious (38% vs. 26%; P < 0.05) or cardiac (19% vs. 7%; P < 0.05) aetiologies. Five-year survival was lower in NASH patients with a high-risk phenotype (age >60 years, body mass index >30kg/m2, with hypertension and diabetes) than in NASH patients without these characteristics (72% vs. 87%; P= 0.02). Subgroup analyses revealed that 5-year overall survival in NASH was equivalent to that in Laennec's cirrhosis (85% vs. 80%; P= 0.87), but lower than that in cirrhosis of cryptogenic aetiology (85% vs. 96%; P= 0.04). ConclusionsOrthotopic LT in NASH was associated with increased early postoperative mortality, but 1-, 3- and 5-year overall survival rates were equivalent to those in non-NASH patients.

Geographical Rural Status and Health Outcomes in Pediatric Liver Transplantation: An Analysis of 6 Years of National United Network of Organ Sharing Data

To determine whether children in rural areas have worse health than children in urban areas after liver transplantation (LT). We used urban influence codes published by the US Department of Agriculture to categorize 3307 pediatric patients undergoing LT in the United Network of Organ Sharing database between 2004 and 2009 as urban or rural. Allograft rejection, patient death, and graft failure were used as primary outcome measures of post-LT health. Pediatric end-stage liver disease/model of end-stage liver disease scores >20 was used to measure worse pre-LT health. In a multivariate analysis, we found greater rates of allograft rejection within 6 months of LT (OR 1.27; 95% CI 1.05-1.53) and a lower occurrence of posttransplantation lymphoproliferative disorder (OR 0.64; 95% CI 0.41-0.99) in patients in rural areas. The difference in allograft rejection was eliminated at 1 year of LT (OR 1.18; 95% CI 0.98-1.42). Rural location did not impact other outcome measures. We conclude that rural location makes a negative impact on patient health within the first 6 months of LT by increasing the risk for allograft rejection, although patients in rural areas may have lower rates of developing posttransplantation lymphoproliferative disorder. Long-term adverse health effects were not seen.

Oral Cavity Metastasis of Hepatocellular Carcinoma following Liver Transplantation

Liver transplantation (LT) remains the only cure for hepatocellular carcinoma (HCC) in many cases. Over many years, most centers have applied the Milan criteria for selecting cirrhotic patients with HCC for LT. In a new era where several transplant groups are pushing the limits of transplanting HCC outside Milan criteria as an aggressive approach with promising results, we present interesting images of a patient that presented a unique and rare site of HCC metastasis after 36 months of liver transplantation.

School outcomes in children registered in the studies for pediatric liver transplant (SPLIT) consortium

School performance is an important aspect of functional outcomes for pediatric liver transplant (LT) recipients. This longitudinal analysis conducted through the Studies of Pediatric Liver Transplantation (SPLIT) research consortium examines several indicators of school function in these patients. A total of 39 centers participated in data collection using a semistructured questionnaire designed specifically for this study. The survey queried school attendance, performance and educational outcomes including the need for special educational services. Participants included 823 of 1133 (73%) eligible patients, mean age 11.34 +/- 3.84 years, 53% female, median age at LT 4.6 (range 0.05-17.8) years, and mean interval from transplant was 5.42 +/- 2.79. Overall, 34% of patients were receiving special educational services and 20% had repeated a grade, with older participants more likely to have been held back (P = 0.0007). Missing more than 10 days of school per year was reported by one-third of the group, with this level of absence being more common in older participants (P = 0.0024) and children with shorter intervals from LT (P < 0.0001). Multivariate analysis revealed the following factors were associated with the need for special educational services; type of immunosuppression at 6 months post-LT, cyclosporine A (odds ratio [OR] = 1.8, confidence interval [CI] = 1.1-3.1), or other (OR = 4.9, 95% CI = 1.4-17.6) versus tacrolimus, symptomatic cytomegalovirus infection within 6 months of liver transplantation (OR = 3.1, CI = 1.6-6.1), and pretransplant special educational services (OR = 22.5, CI = 8.6-58.4).