Primary Liver Transplantation Research Articles

Primary vs. salvage liver transplantation for biliary atresia: A retrospective cohort study

IntroductionKasai hepatoportoenterostomy is the standard of care for children with biliary atresia, but a majority of patients progress to end-stage liver disease and require a salvage liver transplant. Given the high failure rates of the hepatoportoenterostomy operation, some have advocated for primary liver transplantation as a superior treatment approach. The aim of this study was to compare outcomes of pediatric candidates with biliary atresia listed for primary vs. salvage liver transplantation. MethodsThe SRTR/OPTN database was retrospectively reviewed for all children with biliary atresia listed for liver transplant between March 2002 and February 2021. Candidates were categorized as primary liver transplant if they had not undergone previous abdominal surgery prior to listing and salvage liver transplant if they had. Salvage transplants were further categorized as early failure if listed within the first year of life or late failure if listed at an older age. Results3438 children with biliary atresia were listed for transplant during the study period, with 15% of them listed for a primary transplant, 17% for salvage transplant after early failure, and 67% after late failure. Recipients of salvage liver transplant with late failure had lower bilirubin levels and were less critically ill as demonstrated by MELD/PELD scores and hospitalization status. Correspondingly, these recipients had higher waiting list and graft survival, though this did not remain statistically significant after adjustment in multivariable models. There were no differences in waiting list, recipient, or graft survival with primary vs. salvage liver transplant after early failure. ConclusionKasai hepatoportoenterostomy should remain the standard of care in biliary atresia as it may delay need for transplant beyond the first year of life in a subset of recipients and does not jeopardize subsequent transplant outcomes, even with early failure. Levels of evidenceRetrospective cohort study (Level III)

Effect of magnification in pediatric liver transplantation: Asystematic review and meta-analysis.

Hepatic artery thrombosis (HAT) represents a devastating and often fatal complication of liver transplantation. Due to the small vessel caliber in pediatric patients, the use of an operating microscope has largely become the standard for hepatic artery reconstruction to reduce the rate of HAT. Recent evidence, however, suggests that loupe magnification for anastomosis may be equally effective. We aimed to determine the effect of magnification on the rate of hepatic artery thrombosis in pediatric liver transplantation. A systematic search of the literature was conducted. Thousand eighty-eight unique titles were assessed by two independent reviewers. Studies directly comparing rates of HAT from loupe magnification and operating microscope-assisted anastomoses were eligible for meta-analysis. Among primary transplants, the rate of HAT was 6.0%. Operating microscope anastomosis was associated with a 2.6% decrease in the rate of HAT compared to that of loupe magnification (4.9% and 7.4%, respectively, p<.040). When re-transplants were included, the rate of HAT was 5.8%. Operating microscope anastomosis was associated with a 1.0% decrease in the rate of HAT compared to that of loupe magnification (5.3% and 6.3%, respectively, p<.279). Meta-analysis of eligible studies demonstrated a reduction in the rate of HAT with the use of an operating microscope (p<.03). Anastomosis under an operating microscope may be associated with decreased rates of HAT in children undergoing primary liver transplantation. Further high-quality studies comparing the two techniques are needed.

Treatment outcomes of Hepatoblastoma in a resource challenged setting

Background and Aim: Hepatoblastoma is the most common malignant tumour in the paediatric age group. Successful treatment of these tumours includes a multidisciplinary management based on chemotherapy and surgery. While improved outcomes with standardized protocols have been demonstrated in the west, there remains very little data on the outcome of these patients from the Indian subcontinent. We attempt to bridge this gap by presenting our data on the management and outcomes of hepatoblastoma. Methods: A prospectively collected database of over a decade (2010-2022) of children with hepatoblastoma who were treated at our unit was analyzed. Data regarding the clinical presentation, preoperative management, surgical treatment, postoperative course, trend of AFP and outcomes in terms of survival rate and event free survival analyzed. Results: Of the 79 children with hepatoblastoma, 32 &47 were categorized into SIOPEL high and standard risks (4, 21, 34 & 20 were staged as PRETEXT I, II, III & IV respectively). Their median age at diagnosis was 24 months. The median AFP for standard risk group and high risk groups were 197186 ng/ml and 207070 ng/ml respectively. All children received protocoled neoadjuvant chemotherapy before surgery, followed by appropriate course of adjuvant chemotherapy. 68.3%(n=54) underwent liver resection and 25.3%(n=20) underwent liver transplantation. Five children who developed metastatic disease resistant to chemotherapy were not offered surgery. The median follow-up period was 90 months. 5-year overall survival for high risk and standard risk groups were 66.7% and 95.4 % respectively. Conclusions: This experience shows that excellent outcomes can be achieved for hepatoblastoma, even in a resource-challenged setting. Non-transplant surgical resection can be successful in selected patients and, although technically challenging, is associated with a long-term oncological outcome that appears comparable to that obtained with primary liver transplantation.

NASH vs. Non-NASH HCC within and Beyond Milan Criteria in Liver Transplantation for Hepatocellular Carcinoma

Introduction: With mounting obesity, non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC) is a rising indication for HCC-related liver transplantation (LT). This unique population, often with multiple comorbidities, has potential for worse outcomes post-LT. The study aims to compare post-transplantation overall survival (OS) of NASH HCC versus non-NASH HCC patients using a large, North American cohort. Methods: Adults who received primary LT for HCC between 2008-2018, from the United Network for Organ Sharing transplant registry (UNOS) and University Health Network (UHN) database, were included. Two populations were defined: NASH HCC and non-NASH HCC. Recipient characteristics, transplant-specific variables, post-transplant survival outcomes, and causes of death were compared. Sensitivity analyses were performed for populations within and beyond Milan criteria. Results: 20,709 patients were transplanted for HCC, with 2,075(10.0%) NASH HCC. The proportion of LT for NASH HCC increased annually (P=0.02 UHN, P<0.001 UNOS). NASH HCC patients were older, more often female, had higher body mass index, and higher pre-transplantation model for end-stage liver disease score. The 1-, 3-, and 5-year OS were 90.7%, 83.9%, and 76.3% NASH-HCC versus 91.9%, 82.1%, and 74.9% non-NASH HCC (P=0.89). No OS differences were observed within and beyond Milan. Cardiovascular causes contributed to a greater proportion of deaths in NASH HCC (P<0.001). There were no differences in malignancy- or HCC recurrence-related deaths. Conclusion: The global obesity epidemic will have significant future implications in LT and organ allocation. Despite demographic differences, no post-transplantation survival differences exist between NASH and non-NASH HCC. This justifies equivalent organ allocation, irrespective of NASH status.

Kasai Procedure in Patients Older Than 90 Days: Worth a Cut.

Age at Kasai portoenterostomy (KPE) has been identified as a predictive factor for native-liver survival in patients with biliary atresia (BA). Outcomes of pediatric liver transplantation (LT) have improved over recent years. It has been proposed to consider primary LT as a treatment option for late-presenting BA infants instead of attempting KPE. We present our experience with patients older than 90 days undergoing KPE. A retrospective chart review of patients with BA undergoing KPE at our institution between January 2010 and December 2020 was performed. Patients 90 days and older at the time of surgery were included. Patients' characteristics, perioperative data, and follow-up results were collected. Eleven patients matched the inclusion criteria. Mean age at KPE was 108 days (range: 90-133 days). Postoperative jaundice clearance (bilirubin < 2 mg/dL) at 2-year follow-up was achieved in three patients (27%). Eight patients (73%) received a liver transplant at a mean of 626 days (range: 57-2,109 days) after KPE. Four patients (36%) were transplanted within 12 months post-KPE. Two patients died 237 and 139 days after KPE due to disease-related complications. One patient is still alive with his native liver, currently 10 years old. Even when performed at an advanced age, KPE can help prolong native-liver survival in BA patients and offers an important bridge to transplant. In our opinion, it continues to represent a viable primary treatment option for late-presenting infants with BA.

Usability of intraoperative cine-portogram during liver transplantation in young pediatric patients with biliary atresia.

Pediatric patients with biliary atresia (BA) often present liver cirrhosis-associated portal hypertension and portal vein (PV) hypoplasia. For successful liver transplantation (LT), it is essential to maintain sufficient PV inflow through stenosis-free PV reconstruction with effective ligation of collateral veins. The aim of this study was to assess the clinical usability of intraoperative cine-portogram (IOCP) in young pediatric patients who underwent LT for BA. Medical records of pediatric patients younger than 10years who underwent primary LT for BA from 2018 to 2020 were reviewed. A total of 31 patients had undergone Kasai portoenterostomy soon after birth. Their median ages at Kasai portoenterostomy and LT were 1 and 11months, respectively. Types of LT were living-donor LT in 13, deceased-donor split LT in 15, and deceased-donor whole LT in three patients. PV interposition using an iliac vein homograft was performed in 28 patients receiving partial liver grafts. Side-to-side PV unification venoplasty was performed in three patients undergoing whole LT. All patients underwent ligation of collateral veins. IOCP was performed in 6 (19.4%) patients. Four showed no or faint residual venous collaterals. Collateral vein embolization and endovascular stenting were performed in one patient each. PV insufficiency-free survival rate was 100% at 1year and 93.8% at 3years. All patients are currently alive with a median follow-up period of 23months. Intraoperative cine-portogram can be a useful method for identification and embolization of residual portosystemic collateral veins in young pediatric patients who undergo LT for biliary atresia.

Immunologic benefits of maternal living donor allografts in pediatric liver transplantation: fewer rejection episodes and no evidence of de novo allosensitization.

Pediatric liver transplant (LT) recipients of maternal living liver donor (LLD) grafts have been reported to experience fewer rejection episodes. However, it is unclear whether this benefit translates to reduction in developing donor-specific antibody (DSA) among maternal-LLD recipients. The aim of this study was to compare immunologic outcomes among maternal-LLD, non-maternal-LLD, and deceased donor liver transplant (DDLT) recipients. Children (≤18years) who underwent LT between 1/1998 and 12/2019 at two high-volume LT centers in North America were evaluated. Patients were divided into three groups by type of graft received (maternal-LLD, non-maternal LLD, and DDLT). Clinical variables and outcomes were compared according to each graft type. A total of 450 pediatric primary LT were analyzed: 275 (61.1%) DDLT, 73 (16.2%) maternal-LLD, and 102 (22.6%) non-maternal-LLD. Children receiving LLD grafts were less likely to develop rejection when compared to the DDLT group (DDLT 46.9% vs. maternal-LLD 31.5% vs. non-maternal-LLD 28.4%, p=0.001). There was no difference in rejection rates between maternal and non-maternal-LLD recipients. A higher percentage of maternal-LLD recipients were on immunosuppression monotherapy compared to non-maternal-LLD and DDLT recipients (6.7% vs. 1.2 vs. 2.4%, respectively). A subgroup of 68 patients were tested for DSA post-LT. Maternal-LLD recipients were less likely to develop de novo DSA (maternal-LLD 11.8% vs. non-maternal-LLD 19.3% vs. DDLT 43%, p=0.018). None of the maternal-LLD recipients developed antibody-mediated rejection. These data support the concept of immunologic benefit of maternal-LLD in pediatric LT, with lower rates of rejection and allosensitization post-LT when compared to DDLT recipients.

Patient survival following third time liver transplant in the United States in the MELD era

BackgroundThird time liver transplantation is a technically demanding exercise with variable outcomes in single center series. There has been no national level description of survival following third time liver transplant in the US in the MELD era. MethodsThird time liver transplants between March 1, 2002 and January 1, 2018 in the UNOS dataset were analyzed. ResultsPatient survival among the 240 third time liver transplant recipients in the study at 1, 3, 5, and 10 years (71.8%, 62.4%, 59.1%, 49.5%) was significantly worse compared to primary liver transplant (90.6%, 83.9%, 78.8%, 67.6%; p < 0.001) and retransplant (77.1%, 70.3%, 65.6%, 54.9%; p = 0.014). Recipients who were under 43 years old, not on dialysis, without diabetes, and over 1 month out from their second transplant had acceptable survival at 1, 3, 5, and 10 years (88.5%, 78.4%, 73.6%, 69.7%). ConclusionsWhile redo-redo transplant remains a challenging endeavor, appropriate patient selection can yield acceptable results.

Indications and outcomes of liver transplantation for post-Kasai biliary atresia in young adults.

BackgroundSome young adults have a long survival period with native liver after Kasai portoenterostomy (KPE) for biliary atresia (BA). However, a considerable proportion of these patients require liver transplantation (LT). This study aimed to analyze the indications and outcomes of LT in young adults after a long survival period with native liver after KPE.MethodsWe selected seven patients who were 18 years or older at the time of LT out of 116 BA patients who underwent primary LT from 2008 to 2019 at Asan Medical Center.ResultsThe mean ages at KPE and LT were 2.1±0.9 months and 22.0±5.1 years, respectively. Mean serum total bilirubin level and model for end-stage liver disease score at LT were 7.91±7.22 mg/dL and 15.3±6.0, respectively. The main reasons for LT were liver cirrhosis with portal hypertension-associated complications in five patients and intractable cholangitis in two patients. There were five cases of living donor LT and two cases of deceased donor LT. All the seven patients are currently alive during the mean follow-up period of 74.7±40.9 months. One patient suffered from outflow graft vein obstruction requiring endovascular stenting. Another patient showed core antibody-positivity-induced de novo hepatitis B virus infection, which was well managed with antiviral therapy.ConclusionsYoung adult patients with BA are a unique group of patients requiring specialist care regarding transition from pediatric to adult services. The outcomes of LT in young adult BA patients were excellent. Therefore, LT should be considered in patients showing serious BA-associated complications.

Takotsubo syndrome after liver transplantation: An association with intraoperatively administered epinephrine and fentanyl.

Takotsubo syndrome (TTS) can develop after liver transplant (LT), but its predisposing factors are poorly understood. In this study, we aimed to determine if perioperative factors were associated with posttransplant TTS. Adult patients who underwent primary LT between 2006 and 2018 were included. Patients with and without TTS were identified and matched by propensity scores. Of 2181 LT patients, 38 developed postoperative TTS with a mean left ventricular ejection fraction of 25.5% (±7.8%). Multivariable logistic regression revealed two preoperative risk factors (alcoholic cirrhosis and model for end-stage liver disease-sodium scores) for TTS. Post-propensity match analyses showed that TTS patients had significantly higher doses of epinephrine and lower doses of fentanyl during LT compared with non-TTS patients. A higher dose of epinephrine and a lower dose of fentanyl was associated with a higher predicted probability of TTS. All TTS patients had full recovery of cardiac function and had comparable 1-year survival. In conclusion, TTS occurred at a rate of 1.7% after LT and was associated with two pretransplant risk factors. The higher doses of epinephrine and lower doses of fentanyl administered during LT were associated with posttransplant TTS. More studies on the relationship between intraoperative medications and TTS are warranted.

The prognostic significance of serum aspartate transaminase and gamma-glutamyl transferase in liver deceased donors.

The impact of aspartate transaminases (AST) and gamma-glutamyl transferase (GGT) in serum of deceased donors on outcomes after liver transplantation (LT) is unclear. This study aimed to explore the relationship between donor highest AST value or first donor GGT value and graft survival. All consecutive patients who underwent a primary LT in a single center with available donor AST (N = 1253) and GGT value (N = 1152) were included. There was no significant association between donor AST and 90-day graft survival. We found a moderate association between GGT and 90-day graft survival. We found a significant interaction with a donor history of alcohol abuse (HAA). The risk of graft loss was associated with AST and GGT in donors with an HAA but remains unchanged in donors without HAA. There was no difference in graft survival according to donor AST or GGT with a cutoff ≥95th percentile (475 UI/l for AST and 170 UI/l for GGT). However, graft survival was significantly decreased when donors combined GGT ≥ 170 UI/l and HAA (61% at one year). Hepatic grafts from donors with high AST or high GGT but without alcohol history and no additional risk factors can be transplanted in low-risk recipient.

Novel Composite Endpoint for Assessing Outcomes in Liver Transplantation: Arterial and Biliary Complication-Free Survival.

Transplant and patient survival are the validated endpoints to assess the success of liver transplantation (LT). This study evaluates arterial and biliary complication–free survival (ABCFS) as a new metric. ABC, considered as an event, was an arterial or biliary complication of Dindo‐Clavien grade ≥III complication dated at the interventional, endoscopic, or surgical treatment required to correct it. ABCFS was defined as the time from the date of LT to the dates of first ABC, death, relisting, or last follow‐up (transplant survival is time from LT to repeat LT or death). Following primary whole LT (n = 532), 106 ABCs occurred and 99 (93%) occurred during the first year after LT. An ABC occurring during the first year after LT (overall rate 19%) was an independent factor associated with transplant survival (hazard ratio [HR], 3.17; P < 0.001) and patient survival (HR, 2.7; P = 0.002) in univariate and multivariate analyses. This result was confirmed after extension of the cohort to split‐liver graft, donation after circulatory death, or re‐LT (n = 658). Data from 2 external cohorts of primary whole LTs (n = 249 and 229, respectively) confirmed that the first‐year ABC was an independent prognostic factor for transplant survival but not for patient survival. ABCFS was correlated with transplant and patient survival (ρ = 0.85 [95% CI, 0.78‐0.90] and 0.81 [95% CI, 0.71‐0.88], respectively). Preoperative factors known to influence 5‐year transplant survival influenced ABCFS after 1 year of follow‐up. The 1‐year ABCFS was indicative of 5‐year transplant survival. ABCFS is a reproducible metric to evaluate the results of LT after 1 year of follow‐up and could serve as a new endpoint in clinical trials.

Peri-operative risk factors of chronic kidney disease after liver transplantation

Chronic kidney disease (CKD) is a frequent long-term complication after liver transplantation (LT) and is associated with poor long-term survival. The aim of our study was to identify the risk factors of developing post-transplant CKD at 1 year, during the pre-operative, peri-operative, and post-LT phases. All consecutive patients who underwent primary LT between July 2013 and February 2018 were analyzed. To assess the impact of peri- and post-operative factors on renal function at 1 year we performed a propensity score matching on gender, age of the recipient, Model for End-Stage Liver Disease (MELD) score, etiology of the hepatic disease, and estimated Glomerular Filtration Rate (eGFR) at baseline. Among the 245 patients who underwent LT, 215 had available data at one year (Y1), and 46% of them had CKD. Eighty-three patients in the CKD group and 83 in the normal renal function group were then matched. The median follow-up was 35months (27-77). Patients with CKD at Y1 had a decreased 5-year survival compared to patients with normal renal functionat one year: figures were62% and 90%, respectively, p = 0.001. The independent predictors of CKD at Y1 were major complications (OR = 2.2, 95% CI [1.2-4.2]), p = 0.015, intensive care unit (ICU) stay > 5days (OR = 2.2, 95% CI [1.3-5.1]), p = 0.046, ICU serum lactate level at 24h ≥ 2.5mmol/L (OR = 3.8 95% CI [1.1-8]), p = 0.034, need forpost-LT renal replacement therapy (OR = 6.4 95% CI [1.4-25]), and MELD score ≥ 20 (OR = 2.1 95% CI [1.1-3.9]), p = 0.019. The peri-operative period has a major impact on CKD incidence. Early recognition of patients at high risk of CKD may becritical for implementation of nephroprotective measures.

Utility of Preoperative Computed Tomography-Based Body Metrics in Relation to Postoperative Complications in Pediatric Liver Transplantation Recipients.

Computed tomography (CT)‐derived body metrics such as skeletal muscle index (SMI), psoas muscle index (PMI), and subcutaneous fat area index (ScFI) are measurable components of sarcopenia, frailty, and nutrition. While these body metrics are advocated in adults for predicting postoperative outcomes after liver transplantation (LT), little is known about their value in pediatric populations. This study assessed the relation between preoperative CT‐based body metrics and postoperative short‐term outcomes in pediatric LT recipients. Patients aged 0‐18 years who underwent a primary LT were retrospectively included (n = 101; median age 0.5 years; range 0.2‐17.1). SMI, PMI, and ScFI were derived from preoperative axial CT slices. Postoperative outcomes and complications within 90 days were correlated with the CT‐based body metrics. To classify postoperative infections, the Clavien‐Dindo (CD) classification was used. Subgroup analyses were performed for age groups (<1, 1‐10, and >10 years old). An optimal threshold for test performance was defined using Youden’s J‐statistic and receiver operating characteristic curve as appropriate. ScFI was significantly (P = 0.001) correlated with moderate to severe postoperative infections (CD grade 3‐5) in children aged <1 year, with the optimal ScFI threshold being ≤27.1 cm2/m2 (sensitivity 80.4% and specificity 77.8%). A weak negative correlation between SMI and the total duration of hospital stay (R = −0.3; P = 0.01) and intensive care unit (ICU) stay (R = −0.3; P = 0.01) was observed in children aged <1 year. No other associations between CT‐based body metrics and postoperative outcomes were shown. In children aged <1 year with cirrhotic liver disease undergoing LT, preoperative CT‐based body metrics were correlated with moderate to severe postoperative infections (ScFI) and with longer duration of hospital and ICU stay (SMI), and thus can be considered important tools for pre‐LT risk assessment.

Acute Liver Failure Etiology Is an Independent Predictor of Waitlist Outcome but Not Posttransplantation Survival in a National Cohort.

The impact of acute liver failure (ALF) etiology on waitlist (WL) and posttransplantation outcomes, independent of severity of illness, is incompletely characterized. All adults (n=1691) listed for primary liver transplantation (LT) between 2002 and 2019 with ALF due to acetaminophen toxicity (APAP), drug-induced liver injury (DILI), autoimmune hepatitis (AIH), and hepatitis B virus (HBV) were identified in the United Network for Organ Sharing database. ALF etiology was evaluated as an independent predictor of WL mortality and spontaneous survival (SS; versus outcome of LT), as well as post-LT overall survival, graft survival, and in-hospital mortality using multivariable models accounting for differences in clinical parameters at listing. Accounting for severity of illness at listing, WL mortality and SS for DILI, AIH, and HBV were each lower than those for APAP toxicity (adjusted relative risk ratio <1 in all analyses with P<0.001 for both outcomes). ALF etiology was not associated with adjusted overall survival after LT (P=0.09) or graft survival (P=0.13). Inpatient mortality rate after LT was high at 9.0%. While ALF etiology was also not associated with adjusted inpatient mortality (P=0.42), cause of death (COD) was different. For example, the rate of post-LT brain death was 5.3% for APAP toxicity, 3.0% for other DILI, 1.1% for AIH, and 3.0% for HBV (P=0.02). ALF etiology is an independent predictor of WL outcome, even after adjusting for severity of illness, but is not associated with post-LT outcomes with the exception of COD. The majority of post-LT deaths for all ALF etiologies studied occurred during the index hospital stay, suggesting a continued need for enhanced prognostic tools to ensure efficient organ utilization and ALF- and etiology-specific post-LT care to prevent brain death.

The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation.

SummaryHigh‐risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end‐stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low‐risk (0–3), medium‐risk (4–5), and high‐risk (6–10) groups were identified with significantly different 5‐year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high‐risk combinations of recipient‐ and graft‐related factors prognostic for long‐term graft survival after reLT. This tool may serve as a guidance for clinical decision‐making on liver acceptance for reLT.

Risk Factors for Beyond Milan Recurrence After Hepatic Resection for Single Hepatocellular Carcinoma No Larger Than 5 Centimeters.

Hepatic resection (HR) is considered a treatment of choice for a single hepatocellular carcinoma (HCC) ≤5cm in patients with preserved liver function. However, it is possible for these patients to develop a severe form of recurrence (beyond Milan recurrence [BMR] criteria). This recurrence could have been avoided if liver transplantation (LT) was performed primarily, as LT is believed to yield a more favorable oncological outcome compared with HR. The aim of this study was to determine the risk factors for BMR after HR and to verify whether primary LT can provide a more favorable outcome in patients with BMR risk factors. Data from 493 patients who underwent HR for HCC ≤5cm between 1995 and 2016 were analyzed. Among them, 74 patients (15%) experienced BMR. The 10-year survival rate of patients with BMR was significantly low compared with that of patients without BMR (22.6% versus 79.8%; P<0.01). In multivariate analysis, calculated hepatic venous pressure gradient ≥7mm Hg and microvascular invasion were identified as the risk factors for BMR (P<0.05). During the same period, 63 eligible patients underwent LT as a primary treatment for HCC ≤5cm. No significant difference in long-term survival rate was observed when no risk factor for BMR was present in the HR and LT groups (85.5% versus 100%; P=0.39). However, 10-year survival was poorer in the HR group in the presence of risk factors for BMR (60.6% versus 91.8%; P<0.001). Among the patients with HCCs ≤5cm, which are resectable and transplantable, LT is indicated when calculated hepatic venous pressure gradient ≥7mm Hg and/or microvascular invasion is present.

Trends in indications and outcomes of liver transplantation in Canada: A multicenter retrospective study.

The liver transplantation (LT) landscape is continuously evolving. We sought to evaluate trends in indications for LT in Canada and the impact of primary liver disease on post-LT outcomes using a national transplant registry. Adult patients who underwent a primary LT between 2000 and 2018 were retrospectively identified in the Canadian Organ Replacement Registry. Outcomes included post-LT patient and graft survival. A total of 5,722 LTs were identified. The number of LT per year increased from 251 in 2000 to 349 in 2018. The proportion of patients transplanted for HCV decreased from 31.5% in 2000 to 3.4% in 2018. In contrast, the percentage of transplants for HCC increased from 2.3% in 2000 to 32.4% in 2018, and those performed for NASH increased from 0.4% in 2005 to 12.6% in 2018. Year of transplant (per 1year) was protective for both patient (HR:0.96,95%CI:0.94-0.97; P<0.001) and graft survival (HR:0.97, 95%CI: 0.96-0.99; P=0.001). Post-LT outcomes have improved over time in this nationwide analysis spanning 18years. Moreover, trends in the indications for LT have changed, with HCC becoming the leading etiology. The decrease in the proportion of HCV patients and increase in those with NASH has implications on the evolving management of LT patients.

Sequential Treatment of Biliary Atresia With Kasai Hepatoportoenterostomy and Liver Transplantation: Benefits, Risks, and Outcome in 393 Children.

Introduction: Surgical treatment of biliary atresia (BA) is still based on sequential strategy with Kasai hepatoportoenterostomy (KP) followed by liver transplantation (LT), in case of complicated secondary biliary cirrhosis. Concerns have been expressed regarding the risks of LT related to previous KP, suggesting primary LT as an exclusive treatment of BA.Methods: Single-center retrospective analysis including 393 pediatric patients who underwent LT for BA from 1993 to 2018, categorized into two groups: with (KP) or without (NoKP) previous KP. Pre-LT clinical condition was estimated considering age at LT, time on waiting list, pediatric end-stage liver disease score (PELD), and presence of portal vein hypoplasia. Post-LT outcome was evaluated considering patient and graft survival rates, and need for early reoperation due to abdominal or graft-related complications (<45 days after LT).Results: Two-hundred ninety-six patients (75.3%) were categorized in the KP group, and 97 (24.7%) in the NoKP group. Median age at LT was 1.14 years in the KP group and 0.85 years in the NoKP group (p < 0.0001). PELD score was significantly less severe in KP patients (p < 0.05). One-year patient survival rates were 96.9 and 96.8% in the KP and NoKP groups, respectively (p = 0.43), and the corresponding graft survival was 92.5 and 94.8% (p = 0.97). The need for early reoperation was more frequent in the KP group (29.8%) vs. NoKP group (12.4%, p = 0.01). The rate of bowel perforation was non-significantly higher in the KP group (8.1%) vs. NoKP group (3.1%, p = 0.11).Conclusions: The sequential strategy including KP and LT allowed performing LT in patients with significant older age and better clinical conditions, when compared to those transplanted without previous KP. Patient and graft survivals were not impacted by previous KP. Although previous KP was associated with an increased rate of post-LT surgical complications, bowel perforation and bleeding did not occur significantly more frequently. Such results support the current strategy based on sequential treatment.

Risk factors affecting the outcomes in pediatric liver transplantation: A real-world single-center experience

Despite liver transplantation (LT) being the standard treatment for pediatric end-stage liver disease, complications often persist and can adversely affect the post-transplant outcomes. This study aimed to identify the risk factors affecting the outcomes in pediatric LT patients. Data from pediatric patients who underwent primary LT from March 1988 to December 2018 were retrospectively analyzed. Chronic liver disease was defined as an explanted liver showing fibrosis regardless of grade, cirrhosis, or any other underlying disease that may cause progressive liver injury leading to fibrosis or cirrhosis. A total of 255 pediatric patients underwent LT during the study period. Their 1-, 5-, and 10-year overall survival rates were 90.5%, 88.4%, and 87.8%. According to multivariate analysis, while liver disease without underlying chronic liver disease (p = 0.024) and a pediatric end-stage liver disease (PELD) score ≥ 30 (p = 0.036) were the only factors associated with worse survival, body weight < 6 kg (p = 0.050), whole-liver DDLT compared to LDLT (p = 0.001), fulminant liver failure (p = 0.008), and postoperative hepatic artery complications (p < 0.001) were associated with worse graft survival. Liver disease without underlying chronic liver disease was the only factor independently associated with hepatic artery complications (p = 0.003). Greater caution is recommended in pediatric patients with liver disease unaccompanied by underlying chronic liver disease, high PELD score, or low body weight to improve survival after LT. Hepatic artery complication was the only surgical complication affecting the graft survival outcome, especially in patients having liver disease without underlying chronic liver disease.