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.

The Impact of Portal Vein Thrombosis on Liver Transplant Outcomes: Does Grade or Flow Rate Matter?

BACKGROUND: Portal vein thrombosis (PVT) makes the technical aspect of liver transplantation challenging and also affects outcomes. Our aim was to study impact of PVT grade and postreperfusion portal flow on posttransplant outcomes. METHODS: Patients who underwent transplantation with PVT between January 2007 and May 2017 were selected (n = 126). Data on grade of PVT and portal vein flow were collected. Patients were classified into 2 groups; low grade (Yerdel Grade I, n = 73) and high grade (Yerdel Grade II or III, n = 53). Using portal flow rate, patients were divided into high flow (≥1000 mL/min, n = 95) and low flow (<1000 mL/min, n = 31). Additional analyses of flow by graft weight and complications were performed. RESULTS: Postoperatively, incidence of biliary strictures were significantly greater in high-grade PVT compared with low grade (P = 0.02). Incidence of postoperative portal vein thrombosis was higher in low flow after reperfusion compared with high flow (P = 0.02), as was bile leak (P = 0.02). On identifying factors associated with graft loss, moderate to severe ascites preoperatively, high PVT grade and bile leak were associated with worse graft survival. Subanalysis performed combining grade and flow showed that low grade, high flow had the highest graft survival while high grade, low flow had the lowest (P = 0.006). High-grade PVT with low flow also appeared to be an independent risk factor for biliary complications (P = 0.01). CONCLUSIONS: In conclusion, biliary complications, especially strictures are more common in high-grade PVT and graft survival is worse in high-grade PVT and low portal flow.

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.

Effects of Intraoperative Continuous Renal Replacement Therapy on Outcomes in Liver Transplantation.

BACKGROUND: Intraoperative continuous renal replacement therapy (CRRT) may need to be indicated for liver transplant recipients who show renal dysfunction. We aimed to investigate effects of intraoperative CRRT on outcomes after liver transplant. MATERIAL AND METHODS: This study included all adult patients who underwent liver transplant between January 2005 and May 2017 and were found to have renal dysfunction, which was defined as glomerular filtration rate < 30 mL/min at transplant. The patients were divided into 3 groups for outcome analysis: elective CRRT group (renal replacement therapy was already introduced pretransplant, group 1, n = 70), urgent CRRT (intraoperative CRRT was indicated because of unexpected renal dysfunction, group 2, n = 15), and no CRRT group (no intraoperative CRRT even with renal dysfunction, group 3, n = 57). Post-transplant outcomes were analyzed to determine effects of CRRT. RESULTS: Postoperative complication rates were similar in the 3 groups (P = .056). Group 1 showed the highest rate of postoperative renal replacement therapy (86.4% in group 1 vs 66.7% and 10.7% in groups 2 and 3, P < .001). Long-term renal function (at 3, 6, and 12 months post transplant) was similar among the 3 groups (P = .50, .77, and .52, respectively). Group 1 showed a higher risk of 1-year graft loss (hazard ratio, 2.55; P = .03) and mortality (hazard ratio, 2.71; P = .03) than group 3, whereas groups 2 and 3 were similar. CONCLUSION: CRRT used in the urgent setting did not show obvious benefit. Hence, its application should be carefully considered in those who unexpectedly present with acute kidney injury at the time of transplant.

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.

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.

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%.

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.

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.

Should All Status 1A Patients Be Prioritized Over High MELD Patients? Concept of Risk Stratification in Extremely Ill Liver Transplant Recipients.

BACKGROUND: Status 1A patients are prioritized over liver disease patients regardless of Model for End-stage Liver Disease (MELD) score. We aimed to identify groups with high waitlist mortality in Status 1A and MELD ≥40 patients to determine who would most benefit from transplantation. METHODS: Data on patients listed as Status 1A (n = 4447) and MELD ≥40 (n = 3663) over 15 years (2002-2017) was obtained from United Network for Organ Sharing/Organ Procurement and Transplant Network registry. They were divided into 2-derivation and validation groups. Risk factors associated with 28-day waitlist mortality were identified in derivation group and provided risk scores to divide patients into risk groups. Score system was applied to validation group to check its applicability. RESULTS: Risk factors for waitlist mortality in Status 1A included life support, performance status, severe coagulopathy, severe hypo or hypernatremia, and grade 3-4 encephalopathy. Risk factors in MELD ≥40 included higher MELD scores (≥45), age, sex, race, life support, and encephalopathy. On comparing 7- and 28-day mortality, both were higher in Status 1A and MELD ≥40 high-risk groups compared with low-risk groups in the derivation group (P < 0.001). Probability of transplantation was lowest for high-risk MELD ≥40 patients compared with all other groups (P < 0.001). These findings were reproduced in the validation set. Our proposed risk stratification system also showed acceptable 1-year graft and patient survival in high-risk groups. CONCLUSIONS: Our risk scoring system for extremely ill liver transplant candidates successfully stratified risk of waitlist mortality. Waitlist outcomes might be improved by modifications involving categorization of patients based on the presence/absence of risk factors.

α-Smooth muscle actin expression predicts the outcome of Kasai portoenterostomy in biliary atresia.

BACKGROUND/AIMS: Biliary atresia (BA) is a cholangio-destructive disease of the infant liver presenting with features of obstructive cholangiopathy. The Kasai portoenterostomy (KPE) is the first line of management. The aim of our study was to identify the characteristic features of liver histology in BA that impact the outcome of KPE. PATIENTS AND METHODS: Data from 30 consecutive children was retrieved from our prospectively maintained database of children undergoing KPE. This included basic demographics, laboratory values and histopathological data from liver biopsy. The stages of fibrosis, presence of ductal plate malformation (DPM), giant cell transformation, extramedullary hematopoiesis and area percentage of α-SMA (α-smooth muscle actin) expression was correlated with jaundice clearance after KPE using standard statistical tests. Native liver survival was computed. RESULTS: Overall, 13 (43%) children cleared jaundice in this series and 10 (33%) are alive with native liver. Lower area percent expression of α-SMA correlated with increased probability of jaundice clearance after KPE (P < 0.001). There was no correlation between stage of fibrosis and jaundice clearance (P = 0.52). DPM, giant cell transformation and extramedullary hematopoiesis did not correlate with outcome. All children who are alive with native liver had lower expression of α-SMA. CONCLUSION: α-SMA expression may be a potential predictor of jaundice clearance and native liver survival after KPE.

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.

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.

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.

Thrombocytopenia after liver transplantation: Should we care?

Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation (LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in platelet counts of 60%; platelet count recovers to preoperative levels approximately two weeks after LT. The putative mechanisms include haemodilution, decreased platelet production, increased sequestration, medications, infections, thrombosis, or combination of these processes. However, the precise mechanisms remain unclear. The role of platelets in liver transplantation has been highlighted in recent years, and particular attention has been given to their effects beyond hemostasis and thrombosis. Previous studies have demonstrated that perioperative thrombocytopenia causes poor graft regeneration, increases the incidence of postoperative morbidity, and deteriorates the graft and decreases patient survival in both the short and long term after liver transplantation. Platelet therapies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist, platelet transfusion, splenectomy, and intravenous immunoglobulin treatment might have a potential for improving graft survival, however clinical trials are lacking. Further studies are warranted to detect direct evidence on whether thrombocytopenia is the cause or result of poor-graft function and postoperative complications, and to determine who needs platelet therapies in order to prevent postoperative complications and thus improve post-transplant outcomes.

Brincidofovir as Salvage Therapy for Adenovirus Disease in Intestinal Transplant Recipients.

BACKGROUND: Adenoviruses are double-stranded DNA viruses that typically cause mild self-limiting respiratory, ocular, and gastrointestinal infections. In immunocompromised patients, especially transplant recipients, the infection can be severe, with dissemination and multiorgan failure. In intestinal transplant recipients, the incidence is as high as 57%. To our knowledge, no standardized guidelines or U.S. Food and Drug Administration-approved medications exist for the treatment of adenovirus disease. AIMS: We describe two isolated intestinal transplant recipients who developed adenovirus disease (viremia with viral enteritis) that was managed with a new experimental drug, brincidofovir (an oral lipid conjugate prodrug of cidofovir), as salvage therapy. RESULTS: The first patient was a 44-year-old woman who developed adenoviral enteritis 1 month after transplantation, which resolved with ribavirin therapy. Two weeks later, the infection recurred, and brincidofovir was initiated. While receiving this therapy for 3 months, she developed severe acute rejection, which was managed with rabbit antithymocyte globulin followed by infliximab. Eventually, complete resolution of the rejection and adenoviral enteritis was achieved. At 12 months posttransplantation, the patient was healthy and tolerating enteral feeding. The second patient was a 28-year-old man who had undergone isolated intestinal transplantation 6 years before he presented with generalized weakness and an increased ostomy output; he was diagnosed with adenoviral enteritis. Maintenance immunosuppression was reduced, and brincidofovir was started. The infection resolved with a month of therapy. Six months after the infection, he was healthy and tolerating enteral feeding. CONCLUSION: This is the first publication, to our knowledge, to describe two cases in which brincidofovir was used to successfully treat adenovirus infection in intestinal transplant recipients. Thus, these cases demonstrate that brincidofovir appears to be a safe and effective option in the management of adenoviral enteritis in these patients.

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.

Perioperative Ketorolac Use: A Potential Risk Factor for Renal Dysfunction After Live-Donor Nephrectomy.

BACKGROUND Ketorolac is a nonsteroidal anti-inflammatory drug indicated for pain control after surgeries in many fields. The aim of this study was to evaluate the impact of ketorolac use after live-donor nephrectomy (LDN). MATERIAL AND METHODS We reviewed data on 251 patients who underwent laparoscopic LDN from April 2008 to March 2016. Ketorolac was given to 167 patients intraoperatively or postoperatively within 24 h after LDN. Glomerular filtration rate (GFR) percentage was defined as postoperative GFR/preoperative GFR. GFR and GFR percentage at 2 weeks, 6 months, and 1 year after LDN were compared between patients with and without ketorolac administration. Multivariate analysis was performed to identify risk factors for low GFR percentage 1 year after LDN. RESULTS GFR at 1 year was significantly lower in patients who received ketorolac than in those who did not (62 ml/min/1.73 m² vs. 73 ml/min/1.73 m², P<0.01). The differences in GFR and GFR percentage between 2 weeks and 1 year after LDN was significantly lower in the ketorolac group (GFR; 3.0 ml/min/1.73 m² vs. 14.0 ml/min/1.73 m², P<0.01; GFR percentage; 2.0% vs. 12.0%, P<0.01). Urinary albumin/creatinine ratio 1 year after LDN was significantly higher in the ketorolac group compared to the non-ketorolac group (8.6 mg/g vs. 12.6 mg/g, P=0.02). Multivariate analysis revealed that ketorolac use was an independent risk factor for low GFR percentage 1 year after LDN (odds ratio 1.38). CONCLUSIONS Ketorolac appears to be a risk factor for renal dysfunction in the long term after LDN. Prospective clinical trials are needed to reassess its safety.

Extrahepatic metastasis of hepatocellular carcinoma to the paravertebral muscle: A case report.

Identification of extrahepatic metastases (EHM) of hepatocellular carcinoma (HCC) has been paradoxically increasing due to an increase in the survival of HCC patients. However, metastasis of HCC to the skeletal muscle tissue is extremely rare. We describe a unique case of HCC metastasizing to the paravertebral muscle. A 55-year-old man with a history of hepatitis B cirrhosis underwent partial liver resection with complete removal of HCC. Three months later, a computed tomography (CT) scan showed intrahepatic recurrence. The tumors were treated with yttrium-90 microspheres, trans-catheter arterial chemoembolization, and sorafenib. Six months later, a CT scan showed an enhancing lesion of the left paravertebral muscle that on biopsy were consistent with metastatic HCC. The tumor was treated with stereotactic hypo-fractionated image-guided radiation therapy (SHFRT). A follow-up scan 3 mo post-radiotherapy revealed a stable appearance of the paravertebral muscle metastasis. Because of the progression in the intrahepatic tumors, the patient was treated with capecitabine, which was changed to dasatinib 6 mo later. The patient passed away three years after the primary surgical resection. Management of EHM poses an extreme challenge. This is the first case of HCC with EHM to the paravertebral muscle in which stability of disease was achieved using SHFRT. This case highlights the importance of early detection of hepatitis B viral infection and initiation of anti-viral therapy to decrease recurrence of HCC and prevent EHM.