Pediatric liver transplantation (pLTx) has been the standard of care for children with liver failure since the 1980s. This study examined the world's largest single-center experience and aimed to ...identify unique preoperative predictors of early graft and patient survival for primary transplantation (1°-pLTx) and retransplantation (Re-pLTx).
We conducted an IRB-approved, retrospective study of all consecutive, isolated pLTx patients 18 years of age or younger. Twenty-eight demographic, laboratory, and perioperative variables were analyzed as potential outcome predictors. Univariate and multivariate analyses were performed using log-rank test and Cox's proportional hazards model.
There were 806 children who received 1,016 isolated pLTx between February1984 and June 2017. Median follow-up was 12 years. Leading indications for pLTx were cholestatic liver disease (40%), re-pLTx (21%), and fulminant hepatic failure (14%). Seventy-three percent received cadaveric whole grafts. Overall graft and patient survival rates at 0.5, 1, 5, 10, and 20 years were: 76%, 73%, 67%, 63%, 53%, and 87%, 86%, 81%, 78%, 69%, respectively. Relative to 1°-pLTx, re-pLTx recipients were significantly older, larger, with worse renal function, and more likely to be awaiting pLTx in an ICU. Independent significant predictors of graft survival for 1°-pLTx included weight, transplantation era, and renal replacement therapy; for re-pLTx, warm ischemia time and time between 1°-pLTx and re-pLTx. Independent significant predictors of patient survival were renal function, mechanical ventilation, and etiology of liver disease.
This is the largest reported single-center experience of pLTx with substantial follow-up time and a large re-pLTx experience. Important transplant predictors of graft survival include weight, renal function, modern era, warm ischemia time, and time between primary transplantation and re-pLTx. Renal function, mechanical ventilation, and underlying cause of liver disease affect patient survival. Awareness of these factors can help in the decision making for children requiring pLTx.
Although checkpoint inhibitor therapies have demonstrated significant efficacy in many malignancies, they have not been well studied in patients with a history of solid organ transplant. We describe ...two patients with recurrent, refractory, and progressive advanced fibrolamellar hepatocellular carcinoma (HCC) following orthotopic liver transplantation who received programmed cell death protein 1 (PD‐1) inhibitor, nivolumab, on a patient access, off‐label basis. Both rapidly developed irreversible acute liver rejection shortly after starting therapy, and ultimately died. While checkpoint inhibitors clearly have tremendous potential as a targeted therapy, they should be avoided or used with extreme caution in the context of an organ transplant.
The purpose of this study was to identify significant, independent factors that predicted 6 month patient and graft survival after pediatric liver transplantation.
The Studies of Pediatric Liver ...Transplantation (SPLIT) is a multicenter database established in 1995, of currently more than 4000 US and Canadian children undergoing liver transplantation. Previous published analyses from this data have examined specific factors influencing outcome. This study analyzes a comprehensive range of factors that may influence outcome from the time of listing through the peri- and postoperative period.
A total of 42 pre-, peri- and posttransplant variables evaluated in 2982 pediatric recipients of a first liver transplant registered in SPLIT significant at the univariate level were included in multivariate models.
In the final model combining all baseline and posttransplant events, posttransplant complications had the highest relative risk of death or graft loss. Reoperation for any cause increased the risk for both patient and graft loss by 11 fold and reoperation exclusive of specific complications by 4 fold. Vascular thromboses, bowel perforation, septicemia, and retransplantation, each independently increased the risk of patient and graft loss by 3 to 4 fold. The only baseline factor with a similarly high relative risk for patient and graft loss was recipient in the intensive care unit (ICU) intubated at transplant. A significant center effect was also found but did not change the impact of the highly significant factors already identified.
We conclude that the most significant factors predicting patient and graft loss at 6 months in children listed for transplant are posttransplant surgical complications.
Immunosuppression withdrawal can be safely performed in select liver transplantation recipients, but the long‐term outcomes and sustainability of tolerance have not been well studied. We completed a ...10‐year prospective, observational study of 18 pediatric liver transplantation recipients with operational tolerance to (1) assess the sustainability of tolerance over time, (2) compare the clinical characteristics of patients who maintained versus lost tolerance, (3) characterize liver histopathology findings in surveillance liver biopsies; and (4) describe immunologic markers in patients with tolerance. Comparator patients from two clinical phenotype groups termed “stable” and “nontolerant” patients were used as controls. Of the 18 patients with operational tolerance, the majority of patients were males (n = 14, 78%) who were transplanted for cholestatic liver disease (n = 12, 67%). Median age at transplantation was 1.9 (range, 0.6–8) years. Median time after transplantation that immunosuppression had been discontinued was 13.1 (range, 2.9–22.1) years. As many as 11 (61%) maintained tolerance for a median of 10.4 (range, 1.9–22.1) years, whereas 7 (39%) lost tolerance after a median of 3.2 (range, 1.5–18.6) years. Populations of T regulatory cells (%CD4+ CD25hi CD127lo) were significantly higher in patients with tolerance (p = 0.02). Our results emphasize that spontaneous operational tolerance is a dynamic and nonpermanent state. It is therefore essential for patients who are clinically stable off immunosuppression to undergo regular follow‐up and laboratory monitoring, as well as surveillance biopsies to rule out subclinical rejection.
Adolescence: Challenges and responses McDiarmid, Sue V.
Liver transplantation,
November 2013, 2013-Nov, 2013-11-00, 20131101, Letnik:
19, Številka:
S2
Journal Article
The role of donor-specific HLA antibodies (DSA) after pediatric liver transplantation (LTx) is not clearly established. We completed a cross-sectional study to characterize DSA in long-term survivors ...of pediatric LTx and assess the impact of C1q-binding DSA on allograft outcomes.
Serum samples were collected at routine clinic visits from 50 pediatric LTx recipients classified into 3 clinical phenotypes: nontolerant (n = 18) with de novo autoimmune hepatitis (DAIH) and/or late acute cellular rejection (ACR); stable (n = 25) on maintenance tacrolimus; operationally tolerant (n = 7). Samples were blinded, and antibody detection was performed using Luminex single antigen class I and II beads. Patients with positive DSA were tested for C1q-binding DSA.
DSA were detected in 54% (n = 27) of the patients, with the majority directed at HLA class II antigens (DR, 41%; DQ, 53%). Patients with DSA were younger at the time of LTx (P = 0.016) and time of study (P = 0.024). Mean aspartate aminotransferase, alanine aminotransferase, total bilirubin, and gamma glutamyl transferase were higher in DSA-positive patients, though did not reach statistical significance. Nontolerant patients were significantly more likely to have DQ DSA (61%) compared to stable (20%) and tolerant (29%) patients (P = 0.021). The nontolerant phenotype was associated with DSA and C1q-binding DSA, with odds ratios of 13 (P = 0.015) and 8.6 (P = 0.006), respectively. The presence of DQ DSA was associated with DAIH and late ACR, with odds ratios of 12.5 (P = 0.004) and 10.8 (P = 0.006), respectively.
Allograft dysfunction is not always evident in patients with DSA, but DQ DSA are strongly associated with DAIH, late ACR, and chronic rejection.
To analyze a 28-year single-center experience with orthotopic liver transplantation (OLT) for patients with irreversible liver failure.
The implementation of the model for end-stage liver disease ...(MELD) in 2002 represented a fundamental shift in liver donor allocation to recipients with the highest acuity, raising concerns about posttransplant outcome and morbidity.
Outcomes and factors affecting survival were analyzed in 5347 consecutive OLTs performed in 3752 adults and 822 children between 1984 and 2012, including comparisons of recipient and donor characteristics, graft and patient outcomes, and postoperative morbidity before (n = 3218) and after (n = 2129) implementation of the MELD allocation system. Independent predictors of survival were identified.
Overall, 1-, 5-, 10-, and 20-year patient and graft survival estimates were 82%, 70%, 63%, 52%, and 73%, 61%, 54%, 43%, respectively. Recipient survival was best in children with biliary atresia and worst in adults with malignancy. Post-MELD era recipients were older (54 vs 49, P < 0.001), more likely to be hospitalized (50% vs 47%, P = 0.026) and receiving pretransplant renal replacement therapy (34% vs 12%, P < 0.001), and had significantly greater laboratory MELD scores (28 vs 19, P < 0.001), longer wait-list times (270 days vs 186 days, P < 0.001), and pretransplant hospital stays (10 days vs 8 days, P < 0.001). Despite increased acuity, post-MELD era recipients achieved superior 1-, 5-, and 10-year patient survival (82%, 70%, and 65% vs 77%, 66%, and 58%, P < 0.001) and graft survival (78%, 66%, and 61% vs 69%, 58%, and 51%, P < 0.001) compared with pre-MELD recipients. Of 17 recipient and donor variables, era of transplantation, etiology of liver disease, recipient and donor age, prior transplantation, MELD score, hospitalization at time of OLT, and cold and warm ischemia time were independent predictors of survival.
We present the world's largest reported single-institution experience with OLT. Despite increasing acuity in post-MELD era recipients, patient and graft survival continues to improve, justifying the "sickest first" allocation approach.
Postoperative biliary complications have been reported to occur in 10% to 33% of pediatric liver transplantation (LT) recipients. Percutaneous intervention has become the primary treatment method for ...these complications; however, the efficacy and outcomes of these patients have not been well studied. Institutional pediatric LT from 1998 to 2019 were retrospectively reviewed to determine the patients referred for percutaneous treatment of post‐LT biliary strictures. Clinical parameters, percutaneous transhepatic cholangiograms (PTCs), biliary catheter placement, cholangioplasty, and long‐term outcomes were analyzed. Of the 396 consecutive pediatric LT recipients during our study period, 50 (12.6%) were diagnosed with biliary strictures on PTC. LT biliary reconstructions were Roux‐en‐Y hepaticojejunostomy in 28 patients (56%), choledochojejunostomy in 11 patients (22%), and choledochocholedochostomy in 11 patients (22%). Median age at LT was 23.2 months (interquartile range IQR, 10.9‐90.6), and 14 patients (28%) developed hepatic artery thrombosis. A total of 44 patients (88%) were treated with internal/external biliary catheters, of whom 38 (76%) underwent balloon cholangioplasty. By 12 months, 84% of patients had complete stricture resolution and catheter removal. Median total duration of catheter drainage was 152 days (IQR, 76‐308). A total of 8 patients required additional surgery (biliary reconstruction or repeat LT re‐LT) or died with a drainage catheter in place from complications unrelated to PTC intervention. Among the 6 patients (12%) treated with unilateral external biliary drainage catheters, 2 had catheters removed for inadequate drainage but then had spontaneous biliary obstruction resolution, 1 underwent duct reconstruction, and 3 required long‐term catheterization. Biliary strictures following pediatric LT can be successfully treated with internal/external biliary drainage catheters and cholangioplasty if the stricture can be crossed. However, patients with isolated strictured ducts may require long‐term external catheter drainage until re‐LT or percutaneous obliteration of isolated ducts.
To evaluate patient survival and allograft function and health-related quality of life (HRQOL) 20 years after orthotopic liver transplantation (LT).
Although LT is the established treatment of choice ...for acute and chronic liver failure, allograft function and recipient HRQOL 20 years after LT remain undefined.
We performed a prospective, cross-sectional study of LT recipients surviving 20 years or more. Clinical data were reviewed to identify factors associated with 20-year survival. Survivors were directly contacted and offered a survey to assess HRQOL (SF-36; Liver Disease Quality of Life), social support, and cognition (Neuropsychological Impairment Scale). Logistic regression analysis was performed to identify clinical factors influencing HRQOL 20 years after LT.
Between February 1, 1984 and December 31, 1988, a total of 293 patients (179 adults, 114 children) received 348 LTs. Of the 293 patients, 168 (56%) survived for 20 years or more. Actuarial 20-year survival was 52% (patient) and 42% (graft). Factors associated with 20-year survival included recipient age <18 (P = 0.01), nonurgent LT (P = 0.01), no retransplantation (0.02), female gender (0.03), absence of biliary complications (P = 0.04), and short total ischemia time (P = 0.05). Rejection episodes were seen in a greater proportion of 20-year survivors than in nonsurvivors (35% vs. 27%; P = 0.3). Of the 168 survivors, 87 were contacted, and 68 (78%) completed the HRQOL surveys. Compared with the general population, survivors had lower physical scores (P < 0.01) but comparable mental scores on the SF-36. Overall HRQOL was significantly better in 20-year survivors than in patients with chronic liver disease, congestive heart failure, or diabetes. Clinical factors associated with improved post-LT HRQOL were younger age at LT, allograft longevity, and strong social support. More than 90% of pediatric survivors completed high school. After LT, 34% of pediatric recipients married, and 79% remained married at 20 years' follow-up.
More than 50% of LT recipients survive 20 years, achieve important socioeconomic milestones, and report quality of life superior to patients with liver disease or other chronic conditions. LT is a durable surgery that restores both long-term physiologic and psychologic well-being in patients with end-stage liver disease.
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