Disease-specific waitlist outcomes in liver transplantation - a retrospective study.

This study aimed to evaluate possible discrepancies in waitlist outcomes between liver diseases, including alcohol-related liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis C virus infection (HCV), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). Patients registered for liver transplantation from January 11, 2016, to June 30, 2018, were evaluated using OPTN/UNOS registry. Waitlist outcomes were compared between the five-disease groups. Patients were categorized by initial MELD-Na-score (6-20, 21-29, and ≥30) to identify outcome variations. Prognostic impact of transplantation was assessed according to final MELD-Na scores using Cox regression analysis modeling transplantation as a time-dependent covariate. 6053 with ALD, 3814 with NASH, 1558 with HCV, 602 with PBC, and 819 with PSC were eligible. Compared to ALD with comparable MELD-Na-scores, NASH with lower [adjusted hazard ratio (aHR) = 1.30, P = 0.042] and mid-scores (aHR = 1.35, P = 0.008) showed significantly higher risk of 1-year waitlist mortality, and PBC with higher scores showed significantly higher risk of 90-day (aHR = 1.69, P = 0.03) and 1-year waitlist mortality (aHR = 1.69, P = 0.02). Positive prognostic impact of transplantation was not seen until score of 24-27 in ALD, 18-20 in HCV, 15-17 in NASH, and 24-27 in PBC and PSC. There are significant differences in waitlist outcomes among etiologies, which may differ the optimal transplant timing.

Increased Risk of Death in First Year After Liver Transplantation Among Patients With Nonalcoholic Steatohepatitis vs Liver Disease of Other Etiologies.

BACKGROUND & AIMS: An increasing number of patients with non-alcoholic steatohepatitis (NASH) require liver transplantation. We compared outcomes of patients with liver diseases of different etiologies (NASH, hepatitis C virus [HCV]-associated liver disease, and alcohol-associated liver disease [ALD]). METHODS: We analyzed data from the United Network for Organ Sharing registry on 6344 patients who underwent liver transplantation for NASH, 17,037 for cirrhosis from chronic HCV infection, and 9279 for ALD. We collected data from patients who underwent liver transplantation during the following time periods: 2008-2010, 2011-2013, 2014-2015, 2016-2017. We compared outcomes of different groups using Cox regression models, adjusting for donor and recipient characteristics. RESULTS: For patients who underwent liver transplantation during 2016-2017, a significantly lower proportion of patients with NASH survived for 1 year after transplantation than patients with HCV (P = .004) or ALD (P < .001). During this time period, the adjusted risk of death within 1 year was significantly higher for patients with NASH than with ALD (hazard ratio, 1.37; P = .03), regardless of the presence of hepatocellular carcinoma. The effects of increasing age were greatest among patients with NASH: compared to patients younger than 50 years, hazard ratios for overall mortality were 1.31 for patients 50-59 years (P = .02), 1.66 for patients 60-64 years (P < .001), 2.08 for patients 65-69 years (P < .001), and 2.66 and for patients and ≥70 years (P < .001). Mortality from cardiovascular or cerebrovascular disease(s) was highest among patients with NASH, accounting for 11.5% of deaths, compared to 7.0% of deaths in patients with HCV infection and 9.6% in patients with ALD (P < .001). CONCLUSIONS: In an analysis of data from patients who underwent liver transplantation during 2016-2017, we found the risk of death within 1 year after transplant was higher among patients with NASH than HCV-associated liver disease or ALD. Risk of death increased with age, and patients with NASH have a higher risk of death from cardiovascular or cerebrovascular disease.

Effects of Allocating Livers for Transplantation Based on Model for End-Stage Liver Disease-Sodium Scores on Patient Outcomes.

BACKGROUND & AIMS: The Model for End-stage Liver Disease and Sodium (MELD-Na) score was introduced for liver allocation in January 2016. We evaluated the effects of liver allocation, based on MELD-Na score, on waitlist and post-transplantation outcomes. METHODS: We examined 2 patient groups from the United Network for Organ Sharing registry; the MELD-period group was composed of patients who were registered as transplant candidates from June 18, 2013 through January 10, 2016 (n = 18,850) and the MELD-Na period group was composed of patients who were registered from January 11, 2016 through September 30, 2017 (n = 14,512). We compared waitlist and post-transplantation outcomes and association with serum sodium concentrations between groups. RESULTS: Mortality within 90 days on the liver waitlist decreased (hazard ratio [HR] 0.738, P < .001) and transplantation probability increased significantly (HR 1.217, P < .001) in the MELD-Na period. Although mild, moderate, and severe hyponatremia (130-134, 125-129, and <125 mmol/L) were independent risk factors for waitlist mortality in the MELD period (HR 1.354, 1.762, and 2.656; P < .001, P < .001, and P < .001, respectively) compared with the reference standard (135-145 mmol/L), these adverse outcomes were decreased in the MELD-Na period (HR 1.092, 1.271 and 1.374; P = .27, P = .018, and P = .037, respectively). The adjusted survival benefit of transplant recipients vs patients placed on the waitlist in the same score categories was definitive for patients with MELD-Na scores of 21-23 in the MELD-Na era (HR 0.336, P < .001) compared with MELD scores of 15-17 in the MELD era (HR 0.365, P < .001). CONCLUSIONS: Liver allocation based on MELD-Na score successfully improved waitlist outcomes and provided significant benefit to hyponatremic patients. Given the discrepancy in transplantation survival benefit, the current rules for liver allocation might require revision.

Peri-transplant lactate levels and delayed lactate clearance as predictive factors for poor outcomes after liver transplantation: A propensity score-matched study.

This study aimed to investigate risk factors for early allograft dysfunction (EAD) and outcomes after liver transplantation (LT), focusing on peri-transplant lactate clearance. We reviewed patients who underwent deceased donor LTs between 2011 and 2014. Lactate levels were checked at reperfusion and at the time of intensive care unit admission. Early lactate clearance was defined as reduction rate of lactate between the times of reperfusion and immediately after LT. Patients were categorized into the normal and delayed clearance groups. We used propensity score matching (PSM) between these two groups to estimate an impact of lactate clearance on incidence of EAD and graft survival. A total of 256 recipients were eligible for this study. Cut-off value of lactate clearance to predict occurrence of EAD was determined at 0.2 mmol/L/h. After PSM, 120 patients in the normal clearance and 36 patients in the delayed clearance group were matched. Delayed lactate clearance was considered as an independent risk factor for EAD (Odds ratio 3.49, P = 0.002). The adjusted hazard of one-year graft loss was significantly increased in the delayed clearance group (hazard ratio 6.69, P = 0.001). In conclusion, peri-transplant delayed lactate clearance may be a strong predictor for EAD and poor liver graft outcomes.

Factors associated with low graft regeneration in the early phase after living donor liver transplantation.

Appropriate graft regeneration after living donor liver transplantation (LDLT) is crucial to avoid small-for-size syndrome. We enrolled 44 recipients who underwent ABO-identical/compatible LDLT from December 2007 to August 2016 and determined possible factors associated with low graft regeneration after LDLT. Liver regeneration was calculated by the ratio of the graft size on postoperative day (POD) 7 ± 1 day (calculated by CT volumetry) to the size of the donated liver at implant. Postoperative outcomes were compared between the low and high regeneration groups. Median regeneration rate was 1.65-fold. Regeneration rate was negatively correlated with graft-to-recipient weight ratio. Postoperative morbidity rates on POD 14-90 were significantly higher in the low group compared with the high group (63% vs 18%, P = .03). Graft and patient survival in the low group were significantly worse than the high group (1-year graft survival 73% vs 100%, P = .002; patient survival 82% vs 100%, P = .01). Cold ischemia time (CIT; per 10 minute; odds ratio [OR] =1.37) and platelet count <60 000/µL on POD 5 (OR = 14.32) were independently associated with low regeneration. In conclusion, longer CIT and postoperative thrombocytopenia were associated with low graft regeneration in the early phase after LDLT, which could consequently lead to poor graft and patient survival.

Emphysematous pyelonephritis in renal allograft related to antibody-mediated rejection: A case report and literature review.

Emphysematous pyelonephritis (EPN) is a rare condition which can rapidly progress to sepsis and multiple organ failure with high mortality. We experienced a rare case of EPN in a renal allograft related to antibody-mediated rejection (AMR). The patient received a deceased donor kidney transplant due to end-stage renal disease secondary to diabetes mellitus. Cross-match test was negative but she had remote history of anti-HLA-A2 antibody corresponding with the donor HLA. Surgery concluded without any major events. Anti-thymoglobulin was given perioperatively for induction. She was compliant with her immunosuppressive medications making urine of 2 L/d with serum creatinine of 1.9 mg/dL at discharge on post-operative day (POD) 6. She did well until POD 14 when she presented to the clinic with features of sepsis, pain over the transplanted kidney area and decline in urine volume with elevated serum creatinine. CT revealed extensive gas throughout the transplanted kidney. Renal scan revealed non-functional transplant kidney with no arterial flow. Based on these findings, a decision to perform transplant nephrectomy was made. At laparotomy, the kidney was completely necrotic. Pathology showed non-viable kidney parenchyma with the tubules lacking neutrophilic casts suggestive of ischemic necrosis. Donor-specific antibody (DSA) returned positive with high intensity anti-HLA-A2 antibody. This is the first case of early EPN in allograft considered to have occurred as a result of thrombotic ischemia secondary to AMR. This case suggests consideration of perioperative anti-B-cell and/or anti-plasma cell therapies for historical DSA and strict post-operative follow-up in immunologically high-risk recipients to detect early signs of rejection and avoid deleterious outcomes.

RNA-seq reveals outcome-specific gene expression of MMP7 and PCK1 in biliary atresia.

The disease phenotype in biliary atresia (BA) is caused by a fibro-inflammatory process leading to destruction of cholangiocytes, obstruction of ductular pathways and eventual progression to liver cirrhosis. The first line of management is a Kasai portoenterostomy (KPE) followed by liver transplantation (LT) in some children. Several factors have been postulated to affect the outcome of KPE and/or the subsequent progression of liver disease. However, no biomarkers have been identified in the liver for BA. We aimed to address this deficit. Whole transcriptome mRNA sequencing was performed for 29 samples (25 BA and 4 Controls) to identify the candidate genes predicting the prognosis of KPE. These results were further confirmed with quantitative Realtime PCR (qPCR). Analysis from RNA-sequencing data identified matrix metalloproteinase7 (MMP7) and phosphoenolpyruvate carboxykinase (PCK1) as potential determinants of the outcome of KPE. MMP7 expression was significantly elevated in patients who failed to clear jaundice after KPE as well as in patients with End Stage Liver Disease (ESLD). In contrast, PCK1 level was upregulated in patients who had successful KPE, while there was a significant down regulation in patients who failed KPE. MMP7 and PCK1 expression patterns had an inverse relation to the outcome of KPE and hence could potentially be used as biomarkers to predict KPE outcome and disease progression, enabling clinicians to design new treatment strategies for BA.

Early Cholangitis after Portoenterostomy in Children with Biliary Atresia.

AIMS AND OBJECTIVES: Biliary atresia (BA) is a cholangiodestructive disease of the biliary tree. The first line of treatment is a Kasai portoenterostomy (PE) following which patients may develop cholangitis. We studied the effect of early cholangitis on the outcome of PE, namely jaundice clearance and early native liver survival (NLS). METHODS: We reviewed the data of all children who developed cholangitis after PE from our prospectively maintained database of children with BA. The standardized treatment of all children in the database is described. The frequency and nature of these episodes were characterized, and the outcome of PE and NLS 1 year after PE was calculated. RESULTS: Of 62 children who underwent PE in our institutions, 27 developed cholangitis. All episodes of cholangitis occurred within 14 months of PE. Of 25 children who cleared jaundice in the overall series, 19 had cholangitis. The incidence of cholangitis was significantly higher in children who cleared jaundice. Nine children who had cholangitis are alive with native livers for more than 1 year after PE. Twelve children had intractable cholangitis. Three of these children are alive with native liver 1 year after PE. CONCLUSION: In our series, cholangitis occurred in most children who cleared jaundice. Furthermore, the 1-year NLS of children who developed cholangitis was 33%.

Age Is Not a Criterion in Patient Selection for Kasai Portoenterostomy.

AIMS: The aim of our study was to compare the outcome of Kasai portoenterostomy (KPE) in children with biliary atresia (BA) older than 90 days to children less than 90 days and to study its safety and efficacy in children older than 90 days. SUBJECTS AND METHODS: Relevant data were collected from our prospectively maintained database of all children with BA who underwent KPE over a 5-year period. Children were divided into two groups: Group 1 ≤90 days and Group 2 >90 days. Data analyzed and compared included total and direct bilirubin, aspartate aminotransferase-to-platelet ratio index (APRI), and the outcome of procedure which was defined as a serum direct bilirubin <2 mg/dl within 6 months after surgery. Standard statistical tests were used for analysis. RESULTS: Out of 62 children, 45 children were in Group 1 and 17 children were in Group 2. Children in Group 2 had similar total and direct bilirubin compared to children in Group 1. APRI, an indicator of fibrosis, was significantly increased in Group 2 (P = 0.08). About 47% of children in Group 2 had Stage III fibrosis on liver histology compared to 22% of children in Group 1. None of the children in Group 2 had synthetic liver failure (refractory ascites, hypoalbuminemia, or coagulopathy unresponsive to Vitamin K) or portal hypertension. KPE was successful in 29.4% of children in Group 2 and 44% in children in Group 1. There was no perioperative mortality in our group. CONCLUSIONS: KPE was successful in a third of children over 90 days of age and can be safely performed in this group. In the absence of synthetic liver failure, age should not be a disqualification for performing KPE.

Impact of abdominal shape on living liver donor outcomes in mini-incision right hepatic lobectomy: Comparison among 3 techniques.

Although minimally invasive techniques for living donor hepatectomy have been developed, the surgical feasibility and limitations remain to be elucidated. The risks and outcomes involved need to be better understood prior to their widespread application. The aim of this study was to assess feasibility of minimally invasive donor hepatectomy by reviewing our experience. A total of 99 living donor liver transplantations performed between 2000 and 2016 were retrospectively reviewed. All 99 living liver donors underwent right hepatectomy. The breakdown of the techniques is as follows: the standard technique in 33 patients; the laparoscopic-assisted minilaparotomy technique (hybrid technique group) in 19 patients; and the upper midline incision technique without laparoscopic assistance (minilaparotomy group) in 47 patients. An association between donor operative outcomes and body habitus, such as body mass index (BMI), abdominal truncal depth (approximated by celiac axis [CA] depth ratio), and umbilical circumference (UC) were assessed. Perioperative factors were compared between the standard technique and the minimally invasive technique. The minilaparotomy group had significantly shorter operative time (P = 0.046) and hospital stay (P = 0.005) than the standard technique group. Postoperative complication rates were similar between the 3 groups (P = 0.16). In the minilaparotomy group, greater BMI (P = 0.02), CA depth ratio (P = 0.04), and UC (P = 0.004) were found to be risk factors for postoperative complications. In the minilaparotomy group, CA depth ratio > 0.41, UC > 90 cm, and BMI > 30 kg/m2 were significantly associated with longer operative time and hospital stay. In the standard technique group, none of the body size factors were associated with postoperative outcomes. In conclusion, the minilaparotomy technique is safe and feasible, though technical difficulties may be encountered when performed on donors with larger body habitus. Ongoing efforts are required to ensure living donor safety. Liver Transplantation 24 516-527 2018 AASLD.

Liver alone or simultaneous liver-kidney transplant? Pretransplant chronic kidney disease and post-transplant outcome - a retrospective study.

The new Organ Procurement and Transplant Network/United Organ Sharing Network (OPTN/UNOS) simultaneous liver-kidney transplant (SLK) policy has been implemented. The aim of this study was to review liver transplant outcomes utilizing the new SLK policy. Liver transplant alone (LTA) and SLK patients between 2009 and 2015 were reviewed. Graft survival and post-transplant kidney function were investigated among LTA patients meeting the chronic kidney disease (CKD) criteria of the new policy (LTA-CKD group). To validate our findings, we reviewed and applied our analysis to the OPTN/UNOS registry. A total of 535 patients were eligible from our series. The LTA-CKD group (n = 27) showed worse 1-year graft survival, compared with the SLK group (n = 44), but not significant (81% vs. 93%, P = 0.15). The LTA-CKD group significantly increased a risk of post-transplant dialysis (odds ratio = 5.59 [95% CI = 1.27-24.7], P = 0.02 [Ref. normal kidney function]). Post-transplant dialysis was an independent risk factor for graft loss (hazard ratio = 7.25, 95% CI = 3.3-15.91, P < 0.001 [Ref. SLK]). In the validation analysis based on the OPTN/UNOS registry, the hazard of 1-year-graft loss in the LTA-CKD group (n = 751) was 34.8% higher than the SLK group (n = 2856) (hazard ratio = 1.348, 95% CI = 1.157-1.572, P < 0.001). Indicating SLK for patients who meet the CKD criteria may significantly improve transplant outcomes.

Outcome of liver transplantation in patients with prior bariatric surgery.

Nonalcoholic fatty liver disease is becoming the leading cause of disease resulting in liver transplantation (LT). As a result of this trend, more LT candidates are presenting with prior history of bariatric surgery (BS). Over the last decade, 960 patients underwent LT at our institution; 11 (1.1%) had prior BS. The most common type of BS was Roux-en-Y gastric bypass (n = 9) with 1 sleeve gastrectomy and 1 jejunoileal bypass. A total of 9 patients underwent LT alone, and 2 underwent simultaneous liver-kidney transplantation. The most common indication for LT was nonalcoholic steatohepatitis (n = 10) with 5 having additional diagnosis of alcoholic liver disease. The 30-day reoperation rate was 36.4% (n = 4); indications were bile duct repair (n = 3) and wound repair (n = 1). In the first 6 months after LT, biliary complications were seen in 54.5% (n = 6) of the patients. Both patient and graft survival rates at 1 and 2 years were 81.8% (n = 9) and 72.7% (n = 8), respectively. A total of 8 patients (72.7%) had indications for liver biopsy after LT; significant macrovesicular steatosis was found in 2 (18.2%). In patients with a history of alcohol consumption, 2 (40.0%) relapsed after LT. Two patients (18.2%) had a history of diet-controlled diabetes before LT; 1 of these patients became insulin dependent after LT. Mean body mass index (BMI) at LT was 31.0 ± 5.7 kg/m2 . Mean BMI at 1, 6, and 12 months after LT was 28.3 ± 5.8, 28.0 ± 3.2, and 31.0 ± 6.6 kg/m2 , respectively. Mean preoperative albumin was 2.6 ± 0.6 mg/dL. Patients showed improvement in albumin after LT, with mean albumin of 2.7 ± 0.6 and 3.2 ± 0.5 mg/dL at 1 and 3 months, respectively. The liver profile was stable after LT, with mean aspartate aminotransferase of 32.9 ± 18.4 and 26.6 ± 19.8 IU/L and alanine aminotransferase of 28.0 ± 17.5 and 30.2 ± 17.0 IU/L at 6 and 12 months, respectively. In conclusion, outcomes of LT patients with prior BS are comparable with other transplant recipients with regards to patient and graft survival and post-LT complication rates. Liver Transplantation 23 1415-1421 2017 AASLD.

Prognostic impact of postoperative low platelet count after liver transplantation.

BACKGROUND: The positive impact of platelets has been recently implicated in liver transplantation (LT). The aim of this study was to determine the risk factors for graft loss and mortality after LT, focusing on perioperative platelet counts. METHODS: We reviewed all deceased donor LT from 2000 to 2012 and enrolled 975 consecutive recipients. The risk factors for graft loss and mortality were analyzed by multivariate analysis, using Cox's regression model. RESULTS: Using cutoff values acquired by receiver operating characteristics curve analysis, multivariate analyses determined that viral hepatitis C (hazard ratio [HR]=1.32), donor age >40 (HR=1.33), higher peak serum alanine aminotransferase (HR=1.01), reoperation within 30 days (HR=1.51), and platelet count <72 500/µL on postoperative day (POD) 5 (HR=1.30) were independent risk factors for graft loss. Viral hepatitis C (HR=1.33), reoperation within 30 days (HR=1.35), and platelet count <72 500/µL on POD 5 (HR=1.38) were independent risk factors for mortality. CONCLUSION: A low platelet count on POD 5 was associated with graft loss and mortality after LT. Platelet count <72 500/µL on POD 5 can be a predictor of poor graft and overall survival. Maintaining higher postoperative platelet counts could potentially improve graft and overall survival rates.

Prediction of biliary anastomotic stricture after deceased donor liver transplantation: the impact of platelet counts - a retrospective study.

Biliary stricture is a common cause of morbidity after liver transplantation (LT). This study aimed to determine the risk factors for post-transplant biliary anastomotic strictures (BAS), focusing on perioperative platelet counts. We enrolled 771 consecutive recipients who underwent ABO-identical/compatible deceased donor LT with duct-to-duct biliary reconstruction from January 2000 to June 2012. BAS was identified in 142 cases. The median time for stricture development was 176 days. Preoperative and postoperative platelet counts within 5 days after LT were significantly lower in patients with BAS than those without BAS. Using cutoff values acquired by the receiver operating characteristic curve analysis, persistent postoperative thrombocytopenia was defined as platelet counts <41 × 1000/µl and <53 × 1000/µl on postoperative day (POD) 3 and POD 5, respectively. Multivariate analysis indicated persistent postoperative thrombocytopenia (OR = 2.38) was the only independent risk factor for BAS. No significant associations were observed in terms of donor and surgical factors. Multivariate analysis demonstrated estimated blood loss (OR = 1.01, per 100 ml) was an independent contributing factor for persistent postoperative thrombocytopenia. We demonstrated low platelet count was associated with progression of post-transplant BAS. Minimizing intraoperative blood loss potentially contributes to maintain post-transplant platelet count, which may reduce incidence of BAS.

Living donor liver transplantation for biliary atresia - An Indian experience.

LT has played a significant role in improving the outcome of children with BA. We review our five-yr experience of LDLT for children with BA. Records of all children who underwent LDLT in our institution over a five-yr period (August 2010-June 2015) were reviewed and those with a primary diagnosis of BA were selected for our study. Data were extracted from a prospectively maintained database. Additional data were collected by review of case notes and imaging studies. Analysis was carried out using standard statistical means. One hundred and thirty-two children underwent LDLT at our center over the study period, of which 58 children (31 females) had a primary diagnosis of BA. Thirty-three (56.9%) children had undergone a prior KPE and 25 (43.1%) had a primary LT. Thirty-four children had at least one post-op complication, of which 13 had minor complications (Clavien grades I and II) and 21 had major complications (Clavien grade >II). Thirty-day survival was 96.6% and one-yr survival was 91.4%. Univariate analysis of variables comparing children who did and did not have a KPE prior to LT showed that age at LT, weight at LT, PELD, and GRWR were significantly different. LDLT provides excellent outcomes in children with BA. Primary LDLT and LT after KPE provide equivalent results, although the former is technically more challenging as the child is younger.

Pediatric hepatocellular carcinoma in a developing country: Is the etiology changing?

HCC is the second most common malignant liver tumor of childhood. It typically affects children with a median age of 10-14 yr on background hepatitis B-related liver disease and is often metastatic or locally advanced at diagnosis. Children below the age of five yr typically constitute <10% of all children with HCC. In these children, it occurs on a background of congenital or metabolic liver disease. The records of all children with HCC who presented to our department over a six-yr study period were reviewed. Twelve patients with a median age of 5.9 yr (range 1.6-15.4) were diagnosed to have HCC. All patients underwent liver transplantation, and none were resected. Eleven patients had background congenital or metabolic liver disease. All five of those with hereditary tyrosinemia type 1 who presented to us were found to have HCC. No patient had hepatitis B-related liver (HBV) disease. Eight (66.7%) patients had incidentally discovered HCC on examination of the explant. Incidentally discovered HCC were smaller, well differentiated, and did not show microvascular invasion compared to those diagnosed preoperatively. There was no recurrence with a median follow-up of five months. The patient demographic for pediatric HCC is changing probably as a consequence of successful immunization against HBV. Younger patients with congenital and metabolic liver disease in whom liver transplantation is the ideal treatment are likely to constitute an ever-increasing proportion of patients with pediatric HCC as HBV disease is controlled or eradicated.

The extended Kasai portoenterostomy for biliary atresia: A preliminary report.

AIMS: In 1955, Professor Morio Kasai first performed a hepatic portoenterostomy. Since then, the procedure has changed the lives of children with biliary atresia (BA). We report our initial experience in performing "extended" Kasai portoenterostomy (KPE), a modification of the original procedure. MATERIALS AND METHODS: Since 2013, we have used the technique of "extended KPE" and prospectively recorded data on all children undergoing this operation. Data on demographics, clinical features, liver function tests, and perioperative cholangiogram findings were collected. Outcome of KPE was measured by Jaundice Disappearance Rate (JDR) and Native Liver Survival Rate (NLSR). We present our preliminary results from a 30-month period (February 2013 to May 2015). RESULTS: Thirty-one children underwent KPE during this period (19 males) and only 1 child had biliary atresia splenic malformation (BASM). The mean age at KPE was 73 ± 24 days. Five (16.1%) children were more than 90 days old at the time of KPE. Fourteen children cleared jaundice (JDR 45.2%). Eleven (35.5%) children developed episodes of cholangitis, of whom 8 had early cholangitis (within 3 months of the operation). The proportion of children who survived with their own liver 6 months after KPE (NLSR) was 84.2%. Of those children older than 90 days, 2 cleared jaundice and have survived with their native livers for more than 16 months. CONCLUSION: In our preliminary report of 31 children, we conclude that the extended KPE leads to increased jaundice clearance and improved NLSR in children with BA.

Liver pathology in severe multidrug resistant 3 protein deficiency: a series of 10 pediatric cases.

Multidrug resistance protein 3 (MDR3) is a hepatocyte canalicular membrane protein encoded by the ABCB4/MDR3 gene located on chromosome 7. Several liver diseases are known to be associated with MDR3 deficiency. The basic defect is reduced secretion of biliary phospholipid causing disturbance in the primary bile composition, leading to injury to biliary epithelium inducing cell death and inflammation. Severe MDR3 deficiency typically presents during the first year of life or early childhood, often progressing to chronic liver disease with cirrhosis and portal hypertension, requiring liver transplantation. Negative MDR3 immunostaining is suggestive of MDR3 deficiency. Herein, we report the clinical and histopathologic features of 10 cases (6 male/4 female) in infants and children with severe MDR3 deficiency (age range of 8 months to 7 years) diagnosed with negative MDR3 immunostaining in hepatic canaliculi. Three cases underwent liver transplantation. The cases showed periportal bridging fibrosis to micronodular cirrhosis, ductular proliferation with bile plugs, and lobular canalicular bile stasis with rosetting. All 3 explant livers demonstrated cystically dilated large ducts with crystallization of cholesterol. One case showed well-differentiated hepatocellular carcinoma. We conclude that MDR3 immunostaining on formalin-fixed and paraffin-embedded sections is a useful tool to diagnose severe MDR3 deficiency in pediatric liver cholestatic disease cases where genetic testing is not available.

Impact of ductal plate malformation on survival with native liver in children with biliary atresia.

PURPOSE: Ductal plate malformation (DPM) like arrays in the liver which resemble the characteristic persistent embryonal ductular structures have been shown to adversely affect the outcome of Kasai portoenterostomy (KPE) in biliary atresia (BA). We studied the impact of DPM on survival with native liver (SNL) in children with BA who underwent liver transplantation (LT) after KPE as well as those who underwent primary LT without KPE. METHODS: Records of children with BA who underwent LT in our institute were reviewed and divided into three groups-Group 1 had primary LT because of delayed diagnosis of BA and synthetic liver failure, Group 2 had LT for synthetic liver failure after a failed KPE, and Group 3 had LT despite clearing jaundice after KPE for other indications. The impact of DPM on SNL was analyzed using standard statistical means. RESULTS: In Group 1 (n = 26) and Group 2 (n = 26), the incidence of DPM was high and was associated with a significantly shorter SNL compared to children with no DPM. The incidence of DPM was significantly lower in Group 3 (n = 13). CONCLUSION: DPM shortens SNL and influences the pathogenesis of disease progression in children with BA who had synthetic liver failure requiring transplantation either because of a failed KPE or due to a delay in diagnosis. Its incidence is low in children who cleared jaundice after KPE and needed transplantation for other indications at a later age. The presence of DPM signifies an adverse outcome for the disease.

Immediate Postoperative Extubation Decreases Pulmonary Complications in Liver Transplant Patients.

BACKGROUND: Fast-track anesthesia in liver transplantation (LT) has been discussed over the past few decades; however, factors associated with immediate extubation after LT surgery are not well defined. This study aimed to identify predictive factors and examine impacts of immediate extubation on post-LT outcomes. METHODS: A total of 279 LT patients between January 2014 and May 2017 were included. Primary outcome was immediate extubation after LT. Other postoperative outcomes included reintubation, intensive care unit stay and cost, pulmonary complications within 90 days, and 90-day graft survival. Logistic regression was performed to identify factors that were predictive for immediate extubation. A matched control was used to study immediate extubation effect on the other postoperative outcomes. RESULTS: Of these 279 patients, 80 (28.7%) underwent immediate extubation. Patients with anhepatic time >75 minutes and with total intraoperative blood transfusion ≥12 units were less likely to be immediately extubated (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = 0.02; OR, 0.11; 95% CI, 0.05-0.21; P < 0.001). The multivariable analysis showed immediate extubation significantly decreased the risk of pulmonary complications (OR, 0.34; 95% CI, 0.15-0.77; P = 0.01). According to a matched case-control model (immediate group [n = 72], delayed group [n = 72]), the immediate group had a significantly lower rate of pulmonary complications (11.1% versus 27.8%; P = 0.012). Intensive care unit stay and cost were relatively lower in the immediate group (2 versus 3 d; P = 0.082; $5700 versus $7710; P = 0.11). Reintubation rates (2.8% versus 2.8%; P > 0.9) and 90-day graft survival rates (95.8% versus 98.6%; P = 0.31) were similar. CONCLUSIONS: Immediate extubation post-LT in appropriate patients is safe and may improve patient outcomes and resource allocation.