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Alcohol-related liver disease (ALD) is one of the most common indications for liver transplantation. However, liver transplantation for alcoholic hepatitis (AH) remains controversial. The morbidity of severe alcoholic hepatitis (SAH) is extremely high, with most of the deaths occurring within the first 2 months. Multiple studies have recently demonstrated significant improvement in overall survival following liver transplantation in patients with SAH who failed medical management, with comparable rates to those transplanted electively. Concerns remain due to the small pool of donors and the high risk of alcohol relapse in this population. The traditional requirement of 6 months of abstinence prior to transplantation, or also known as “6-month rule” is controversial and has been criticized as whether it is a good predictor of long-term sobriety. Previous studies among patients with alcoholic cirrhosis have indicated that this rule poorly identifies patients who will relapse after liver transplantation. More recent studies in patients transplanted for SAH, have reported relapse rates that are comparable to those with abstinence periods >6 months. Applying stringent selection criteria appears to be key in identifying patients who are less likely to relapse after transplantation, and therefore prolonging patient and graft life. However, further research is needed to identify patients at risk and create appropriate screening tools. In this article, we present a review of currently available data on this topic.

Background and Aims: Hepatitis C virus (HCV)-infected organs are underutilized. We aimed to assess the safety and efficacy of direct-acting antiviral agents (DAAs) therapy in HCV viremic patients who are transplanted with a liver from a HCV viremic donor. Methods: We conducted a retrospective study, including patients seen from July 2015 to April 2017. HCV viremic patients transplanted with a liver from a HCV viremic donor and subsequently treated with DAAs were included. Outcomes assessed included undetectable viral load at 12 weeks after completing DAA therapy (sustained virologic response, SVR12), adverse events, and interactions with immunosuppression. Results: Twenty-four HCV viremic recipients received livers from HCV viremic donors. Median age was 63 years, and the majority (79.2%) were genotype 1a. Donors and recipients were viremic at the time of transplant. Median modified model for end-stage liver disease score was 19, and median time on the waitlist was 81 days. Median time from transplant to initiation of DAA therapy was 123 days. Several DAA regimens were used and 15 (62.5%) patients did not receive ribavirin. Treatment duration ranged from 12 to 24 weeks. Twenty-three (95.8%) patients achieved SVR12. Five (20.8%) patients developed adverse events; however, none required DAA discontinuation. Conclusions: DAA therapy was efficacious and well tolerated in HCV viremic recipients who underwent liver transplantation from a HCV viremic donor.

Iliac artery calcification is a common phenomenon complicating renal transplantation, particularly in those with diabetes. The potential for vascular clamp injury can threaten the renal allograft, ipsilateral lower extremity, or both. Utilization of internal balloon occlusion can allow for placement of a “Chimney Patch” graft, fashioned from a deceased donor artery, to the calcified vessel, eliminating the risk of clamp injury and minimizing warm ischemic time. We present a series of 6 patients transplanted with internal balloon occlusion with successful renal and pancreatic allograft function and no ipsilateral vascular complications. Internal balloon occlusion is a safe and effective adjunct for renal or pancreas transplant to prevent clamp injury with no adverse effect on allograft function.

The effect of antiviral therapy (AVT) on kidney function in liver transplantation (LT) recipients has not been well described despite known association of hepatitis C virus (HCV) infection with chronic kidney disease (CKD). We compared the incidence of CKD and end-stage renal disease (ESRD) in 204 LT recipients with HCV based on treatment response to AVT. The mean estimated glomerular filtration rate (eGFR) at baseline (3 months after LT) was similar in the sustained virological response (SVR; n = 145) and non-SVR group (n = 59; 69 ± 21 versus 65 ± 33 mL/minute/1.73 m2 ; P = 0.27). In the unadjusted Cox proportional regression analysis, the presence of SVR was associated with an 88% lower risk of CKD (hazard ratio, 0.12; 95% confidence interval [CI], 0.05-0.31) and 86% lower risk of ESRD (odds ratio, 0.14; 95% CI, 0.05-0.35). Similar results were found after adjusting for propensity score and time-dependent Cox regression analyses. The estimated slopes of eGFR based on a 2-stage mixed model of eGFR were calculated. Patients with SVR had a less steep slope in eGFR (-0.60 mL/minute/1.73 m2 /year; 95% CI, -1.50 to 0.30; P = 0.190) than recipients without SVR (-2.53 mL/minute/1.73 m2 /year; 95% CI, -3.99 to -1.07; P = 0.001), and the differences in the slopes were statistically significant (P = 0.026). In conclusion, in LT recipients with chronic HCV infection, achieving SVR significantly lowers the risk of decline in renal function and progression to ESRD independent of the AVT therapy used.

Supplemental Digital Content is available in the text., Background. The impact of acute-on-chronic liver failure (ACLF) defined by European Association for the Study of the Liver-Chronic Liver Failure in liver transplant (LT) recipients has not been well characterized. The aim of the study was to assess early posttransplant morbidity and survival of ACLF patients. Methods. Eight hundred twenty-five consecutive LT patients (04/2006–03/2013) were included in a retrospective analysis. Of the 690 evaluable patients, 589 had no ACLF, and the remaining 101 were grouped into ACLF Grades 1–3 (ACLF Grade 1: 50 [49.5%], ACLF Grade 2: 32 [31.7%], and ACLF Grade 3: 19 [18.8%]). Results. LT recipients transplanted in the context of ACLF had significantly increased serum creatinine (2.27 ± 1.16 versus 0.98 ± 0.32; P < 0.0001), and inferior 1-year graft (90% versus 78%; P < 0.0001) and patient survival (92% versus 82%; P = 0.0004) by Kaplan-Meier survival analysis; graft and patient survival correlated negatively with increasing severity of ACLF. One-year graft and patient survival were lower in those with high ACLF (Grade 2 and 3) irrespective of Model for End-Stage Liver Disease compared with other groups. The ACLF group had longer intensive care unit stays (10.6 ± 19.5 versus 4.2 ± 9; P < 0.0001), hospital stays (20.9 ± 25.9 versus 11.7 ± 11.4; P < 0.0001), and increased surgical re-exploration (26.7 % versus 14.6%, P = 0.002). Conclusions. Patients with ACLF undergoing LT have significantly higher resource utilization, inferior graft survival and patient survival, and renal dysfunction at 1 year. The combination of ACLF and Model for End-Stage Liver Disease can be considered when determining the suitability for potential transplantation.

Background and aims Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. Approach and results Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. Conclusions Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.

Fibrosing cholestatic hepatitis (FCH) posttransplantation can lead to graft failure and death. In the era of direct acting antiviral therapy (DAA), several studies have demonstrated the efficacy and safety of transplanting hepatitis C virus (HCV)-positive allografts into HCV-negative recipients. In this case series, we present two cases of HCV-negative recipients who underwent kidney transplantation from viremic donors and developed FCH. Both patients presented after transplant with abnormal liver function tests and HCV viral loads of greater than 100 000 000 IU/mL. FCH was diagnosed by histology and/or clinical data. Both patients were started on DAA therapy within 24 hours of admission with improvement in LFTs. One patient has undetectable HCV 12 weeks after completing treatment and the other patient has undetectable HCV after completing DAA treatment. The introduction of DAAs has changed the landscape of solid organ transplantation with the potential to expand the donor pool and increase access to organs. While HCV viremic organs have tremendous potential to increase access to a scarce resource, FCH is a potentially fatal complication and therefore clinicians must maintain a high index of suspicion for this unique complication.

Aim Hepatic sarcoidosis is a rare indication for orthotopic liver transplantation (OLT). Hence, studies evaluating these patients are scarce. We present a single center experience with OLT for hepatic sarcoidosis in a case–control study. Methods A retrospective chart review was performed on 970 patients with OLT at our center, and 13 patients (1.3%) were identified who underwent 14 OLTs for hepatic sarcoidosis. For each case, two controls matched for etiology of liver disease, recipient age (±5 years), and duration since transplant (within 5 years) were selected. Results For the 13 patients transplanted for sarcoidosis, the median age was 46 years. The majority were women (62%) and African-American (85%). Cholestatic liver disease was the primary manifestation. Portal hypertensive complications were present in 11 patients (84%). The median MELD score at transplantation was 19. Extra-hepatic manifestations were present in ten patients (77%). All patients received whole deceased 14 donor allografts. Six patients remain alive with a median post-OLT follow-up of 8.4 years. The 1-, 3-, 5-, and 10-year patient survival rates were 84.6%, 76.9%, 61.1%, and 51.3%, respectively for the sarcoidosis group and 82.1%, 78.6%, 78.6%, and 61.9%, respectively for the matched PSC/PBC group (P = 0.739). Re-graft free survival for sarcoidosis patients was 84.6%, 76.9%, 61.5%, and 51.3% for 1-, 3-, 5-, and 10-years and for the matched control group re-graft free survival was 78.6% at 1-, 3-, 5-years, and 64.8% at 10-years (P = 0.661). Recurrence of hepatic sarcoidosis was found in 4 patients at 11 days, 112 days, 222 days, and 6.6 years. Conclusions Our study depicts the long-term benefit of liver transplantation in patients with end stage liver disease secondary to sarcoidosis. It shows statistically comparable graft and patient survival for such patients when compared to other cholestatic diseases. Disease recurrence, although possible, has not been shown to cause allograft dysfunction.

Background The utility of ex vivo Magnetic resonance imaging proton density fat fraction (MRI-PDFF) in donor liver fat quantification is unknown. Purpose To evaluate the diagnostic accuracy and utility in predicting early allograft dysfunction (EAD) of ex vivo MRI-PDFF measurement of fat in deceased donor livers using histology as the gold standard. Methods We performed Ex vivo, 1.5 Tesla MRI-PDFF on 33 human deceased donor livers before implantation, enroute to the operating room. After the exclusion of 4 images (technical errors), 29 MRI images were evaluable. Histology was evaluable in 27 of 29 patients. EAD was defined as a peak value of aminotransferase >2000 IU/mL during the first week or an INR of ≥1.6 or bilirubin ≥10 mg/dL at day 7. Results MRI-PDFF values showed a strong positive correlation (Pearson’s correlation coefficient) when histology (macro-steatosis) was included (r = 0.78, 95% confidence interval 0.57‐0.89, p

Hepatocellular carcinoma (HCC) occasionally occurs in non-cirrhotic patients; however, outcomes for these patients are not extensively documented. We performed an institutional review of patients without cirrhosis who underwent resection for HCC. Clinical data were evaluated to identify factors impacting recurrence-free survival (RFS) and overall survival (OS). Forty-two patients underwent hepatectomy for HCC in the absence of cirrhosis over a 10-year period. Median follow-up was 22 months. For the entire cohort, 1-, 3-, and 5-year RFS was 62%, 42%, and 38% and 1-, 3-, and 5-year OS was 78%, 60%, and 49%, respectively. On univariate analysis, RFS was significantly worse for patients with a disrupted/absent tumor capsule (p = 0.027), vascular invasion (p = 0.030), elevated alkaline phosphatase (p = 0.004), and tumor size > 10 cm (p = 0.016). OS was significantly worse for patients with a disrupted/absent tumor capsule (p = 0.044), obesity (p = 0.036), and elevated alkaline phosphatase (p = 0.007) with a trend towards decreased OS for tumor size > 10 cm (p = 0.07). Patients undergoing resection for HCC in the absence of cirrhosis have fairly high recurrence and modest survival rates. Pre-operative alkaline phosphatase, tumor size, tumor encapsulation, and vascular invasion are important prognostic factors.

Background Sorafenib has shown survival benefits in patients with advanced HCC; however, limited data are available on its role in OLT recipients with advanced HCC in the explant. Aim Evaluate the role of preemptive sorafenib therapy on HCC recurrence and survival after OLT with advanced HCC on explant pathology. Methods We retrospectively reviewed the outcome after OLT of all HCC recipients with advanced HCC in the explant pathology from 04/2006 to 12/2012 based on preemptive treatment with sorafenib. Results During the observation period, 217 HCC recipients underwent OLT; 50 explants revealed advanced HCC. After exclusion of 5 patients who were lost to follow-up, 45 LT recipients were finally included for analysis. Recipients were grouped as sorafenib Gr (N = 25) and nonsorafenib Gr (N = 20). Both recurrence-free survival (RFS) (P = .67) and overall survival were similar between groups (P = .53) on Kaplan-Meier analysis. Additionally, sorafenib use was neither associated with HCC recurrence-free survival (HR 0.74, 95% CI [0.32-1.70]; P = .48) nor overall survival (HR 0.92, 95% CI [0.39-2.15], P = .84) on multivariate Cox proportional hazard model with sorafenib use as time-varying covariates. Conclusion Preemptive treatment with sorafenib in OLT recipients with high-risk features in explant does not improve HCC recurrence-free or overall survival.

BACKGROUND We have previously documented the efficacy of a steroid-free immunosuppression protocol using rabbit antithymocyte globulin (RATG) induction in orthotopic liver transplantation (OLT) with tacrolimus minimization. The purpose of this report is to demonstrate the benefits of this protocol in a large cohort of patients. METHODS We evaluated outcomes of 500 consecutive OLT recipients who received RATG induction and a single dose of solumedrol given before the first dose of RATG. Mycophenolate mofetil was initiated postoperatively with delayed initiation of tacrolimus. Sirolimus replaced tacrolimus if serum creatinine remained above 2.0 mg/dL by day 7. Patients were weaned to tacrolimus or sirolimus monotherapy at 3 months. Mean model for end-stage liver disease (MELD) at transplantation was 22 ± 6. RESULTS Forty-four percent of patients had hepatitis C. Posttransplant creatinine was highest at 1 month (1.43 ± 0.95 mg/dL) and improved to 1.26 ± 0.60 mg/dL (P < 0.05) at 2.5 years. Glomerular filtration rate was lowest at 1 month (65.6 ± 30.0) and improved by 1 year (72.7 ± 28.2, P < 0.01). Tacrolimus was initiated at 4.79 ± 13.3 days with a level of 4.95 ± 2.45 ng/mL at 1 year. One-year patient and graft survival were 92.8% and 89.6%, respectively, with a 3-year patient survival of 82.9%. Rejection occurred in 114 (22.8%) patients, 33 (6.6%) patients requiring steroids. Univariate and multivariate Cox proportional hazard analyses were performed to evaluate the effects of donor and recipient characteristics on patient and graft survivals. Pretransplant creatinine was consistently a statistically significant predictor for patient and graft survival. CONCLUSION This is the largest reported series of OLT recipients using a steroid-free protocol with RATG induction demonstrating excellent outcomes, low complication rates, and preservation of renal function.

Background Endoscopic treatment of anastomotic biliary stricture (ABS) after liver transplantation (LT) has been proven to be effective and safe, but long term outcomes of early compared to late onset ABS have not been studied. The aim of this study is to compare the long-term outcome of early ABS to late ABS. Methods Of the 806 adult LT recipients (04/2006-12/2012), 93 patients met the criteria for inclusion, and were grouped into non-ABS (No stenosis on ERCP, n=41), early ABS [stenosis < 90 days after LT, 18 (19.3%)], and late ABS [stenosis ≥ 90 days after LT, 34(36.5%)]. A propensity matched control group for the ABS group (n=42) was obtained matched for outcome variables for age, gender, and calculated MELD score at listing. Results Mean number of ERCPs (2.33±1.3 vs. 2.56±1.5, P=0.69) was comparable between the groups; however significantly better long-term resolution of the stricture was noted in the early ABS group (94.44% vs. 67.65%, P=0.04). Kaplan-Meyer analysis revealed worst survival in the early ABS group compared to the non-ABS, late ABS and control groups (P=0.0001). Conclusion LT recipients with early ABS have inferior graft survival despite better response to endoscopic intervention. This article is protected by copyright. All rights reserved.

OBJECTIVES In living-donor liver transplant recipients with hepatitis C virus infection, outcomes of recurrent hepatitis C virus infection and fibrosis progression are not well documented. We evaluated fibrosis progression, response to pegylated interferon treatment, and long-term graft survival in living-donor liver transplant recipients who had hepatitis C virus infection. MATERIALS AND METHODS In 48 transplant recipients, including 29 recipients who had follow-up liver biopsy ≥ 6 months after transplant, histology and clinical courses were reviewed. Outcomes were evaluated for patients grouped into slow and rapid fibrosis groups. Treatment with pegylated interferon and ribavirin was assessed in 18 patients. RESULTS Clinical features were similar between recipients with slow or rapid fibrosis. The time interval from transplant to recurrence of hepatitis C virus infection was significantly shorter in the recipients with rapid fibrosis. Recipients with rapid fibrosis had significantly greater confluent necrosis, acidophil bodies, and fibrosis score than recipients with slow fibrosis. Graft survival rates were similar between patients with slow or rapid fibrosis. Cumulative proportion of long-term graft survival was 60% at 7 years after transplant. Sustained virologic response was noted in 5 of 18 patients (28%) who received pegylated interferon and ribavirin. CONCLUSIONS In recipients of living-donor liver transplant with early recurrence of hepatitis C have worse fibrosis progression but graft survival was not affected. Therapy with pegylated interferon and ribavirin achieved sustained virologic response only in a small proportion of the patients.

Metastatic melanoma is a donor-derived malignancy that has rarely been reported in liver allograft recipients. We present a case of a transmitted donor-derived melanoma to a liver allograft recipient in whom the diagnosis was established by polymerase chain reaction-based DNA fingerprinting. A 52-year-old African-American man underwent a successful orthotropic liver transplant for alcohol-induced cirrhosis. One year after the orthotropic liver transplant, he presented at our institution with diffuse abdominal pain, and a computed tomography scan of the abdomen and chest showed innumerable masses diffusely involving the liver and multiple subcutaneous nodules in the abdominal and chest wall. A liver biopsy confirmed the diagnosis of metastatic melanoma. The origin of melanoma was traced to the donor by DNA fingerprinting of the native liver, the donor liver, and the donor gallbladder. Chemotherapy was initiated with temozolomide (75 mg/m² daily) and thalidomide (50 mg daily), to which he responded within 8 weeks with radiologic improvement in metastatic lesions. Tacrolimus was switched to sirolimus because of renal insufficiency as well as reported effectiveness against melanoma. Our patient survived for 9 months after the diagnosis of metastatic melanoma. He ultimately died of brain metastases. Donor-derived metastatic melanoma is a rare cancer with the highest transmission and mortality rates, which requires better recognition. Prompt diagnosis of donor-derived melanoma is critical and can be achieved reliably with polymerase chain reaction-based DNA analysis. Management options after diagnosis include de-escalation of immunosuppression, with or without urgent organ removal or retransplant. The roles of chemotherapy, immunotherapy, and radiotherapy require further study.

Background Coronary artery disease (CAD) is a significant problem during evaluation for liver transplantation (LT). We aim to assess survival in LT recipients based on presence, severity, extent of CAD, and cardiac events within 90 days of LT. Methods Eighty-seven LT recipients with history of pre-LT angiogram (December 2005 to December 2012) were compared with 2 control groups without prior angiogram, 72 LT recipients matched for cardiovascular risk factors (control group I), and 119 consecutive LT recipients without any CV risk factors (control group II). CAD was assessed by (1) vessel score (≥50% reduction in luminal diameter), and (2) Extent score (Reardon scoring system). Results Of the 87 LT recipients (study group), 58 (66.7%) had none or less than 50% stenosis, 29 (33.3%) had obstructive CAD (≥50% stenosis), 7 (8%) with single-vessel disease, and 22 (25.3%) with multivessel disease. In the study group, irrespective of prerevascularization severity of CAD (P = 0.357), number of segments involved (0, 1-2, > 2 segments, P = 0.304) and extent of CAD based on Reardon score (0, 1-9, >10, P = 0.224), comparable posttransplant survival was noted. Overall, patient survival in the revascularized CAD group was comparable to angiogram group without obstructive CAD, and both control group I and control group II (P = 0.184, Log Rank). Postoperative cardiac events within 90 days of LT predicted poor survival in study group as well as control groups. Conclusions Severity or extent of CAD does not impact post-LT survival, if appropriately revascularized. Early postoperative cardiac events are associated with inferior survival in LT recipients, irrespective of underlying CAD.

Background Nonalcoholic Steatohepatitis (NASH) has become an increasingly important indication for liver transplantation (LT), and there has been a particular concern of excessive cardiovascular-related mortality in this group Methods Using the United Network for Organ Sharing-Standard Transplant Analysis and Research (UNOS-STAR) dataset, we reviewed data on 56,995 adult transplants (January 2002 through June 2013). 3,170 NASH liver-only recipients were identified and were matched with 3,012 non-NASH HCV+ and 3,159 non-NASH HCV- controls [matched 1:1 based on gender, age at LT (±3 years), and MELD score (±3)] Results Cox regression analysis revealed significantly lower hazard of all-cause (HR 0.669; p

Hepatic sarcoidosis is a rare indication for liver transplantation. Using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation Network (OPTN) database, we evaluated patient and graft survival after orthotopic liver transplantation for sarcoidosis between October 1987 and December 2007. We assessed the potential prognostic value of multiple demographic and clinical variables, and we also compared these patients to a case-matched group of patients with primary sclerosing cholangitis (PSC) or primary biliary cirrhosis (PBC). The 1- and 5-year survival rates for the sarcoidosis group were 78% and 61%, respectively, and these rates were significantly worse than the rates for the PSC/PBC group (P = 0.001). Disease recurrence in the liver is a rare cause of graft loss or patient death. Three deaths occurred in the sarcoidosis group because of recurrent hepatic sarcoidosis, and 1 death was a result of cardiac sarcoidosis. A univariate analysis identified an increasing donor risk index as a significant negative factor for outcomes for the sarcoidosis group [hazard ratio (HR) = 2.06, confidence interval (CI) = 1.04-4.06, P = 0.037], but this finding was not found in a multivariate analysis, in which no independent predictors were found to have a significant impact. A case-matched univariate analysis demonstrated that sarcoidosis and morbid obesity were significant negative factors for outcomes, and in a multivariate analysis, sarcoidosis continued to predict worse outcomes (HR = 2.39, CI = 1.21-4.73, P = 0.012). In conclusion, an analysis of the UNOS/OPTN database indicates that the patient and allograft survival rates for hepatic sarcoidosis are satisfactory, but they are worse in comparison with the rates for other cholestatic liver diseases.

Background. Biliary strictures (BS) are common complication after liver transplantation. We aimed to determine the accuracy of magnetic resonance cholagiopancreatography (MRCP) in diagnosing BS in liver transplant recipients (LTRs) when compared to direct cholangiographic methods (endoscopic resonance cholagiopancreatography [ERCP] and/or percutaneous transhepatic cholangiography [PTC]). Methods. Retrospective chart review of 910 LTRs (July 2008 to April 2015) was performed, and a total of 39 patients with duct-to-duct anastomosis (22 males; 56.4%; mean age, 52.8 ± 8.3 years) were included who had an MRCP followed by either ERCP and/or PTC within 4 weeks. A cholangiographic narrowing (on ERCP and/or PTC) that required balloon dilation and/or stent placement was considered a BS and was considered clinically significant if the intervention resulted in at least 30% improvement of bilirubin within 2 weeks. Sensitivity, specificity, accuracy, positive predictive values and negative predictive values of MRCP in diagnosing BS were calculated. Results. Magnetic resonance cholagiopancreatography showed anastomotic BS in 17 of 39 patients, and subsequent ERCP and/or PTC revealed a total of 25 BS (positive predictive value of 0.94). Nine BS on cholangiography (ERCP, 8; PTC, 1) were not detected on earlier MRCP (sensitivity, 0.64; 95% CI, 0.45-0.82); 2 were clinically significant BS and 6 of the remaining 7 had no improvement in their liver function test with biliary intervention. Thirteen LTRs had no BS on either modality (specificity, 0.93; 95% CI, 0.66-0.99). The negative predictive value of MRCP was 0.59 for cholangiographic BS. The overall accuracy of MRCP is 0.74 (exact 95% CI, 0.58-0.87). Inclusion of age, race, and alanine aminotransferase level improved the predictive value of MRCP (area under the curve = 0.94, 95% CI: 0.86-1.00). Conclusions. Magnetic resonance cholagiopancreatography has high specificity but low sensitivity in diagnosing cholangiographic BS in LTRs, although the predictive value further improved with inclusion of age, race, and alanine aminotransferase. Clinical significance of BS in LTRs not identified on MRCP is questionable because ERCP with intervention did not improve their liver function tests in the vast majority.

Obesity, diabetes, and prior abdominal surgery are generally considered to increase the risk of liver transplantation. The aim of the present study was to define the effects of these factors on the immediate outcome after transplantation. Two hundred twenty-one consecutive liver transplants were analyzed. Twenty-eight patients were excluded. In the remaining 193 patients [mean age = 52 ± 19 years, body mass index (BMI) = 28.5, Model for End-Stage Liver Disease (MELD) score at listing = 18.7], the risk from obesity was graded as follows: (0) BMI ≤ 30, (1) BMI = 30-34.9, (2) BMI = 35-39.9, and (3) BMI ≥40. The presence of diabetes and prior abdominal surgery were each given 1 point. All the individual scores for obesity, diabetes, and prior surgery were added to produce a composite risk score for each patient. Patients were categorized into 6 risk groups, group 0 having the least risk and group 5 having the highest risk (none of the patients were in group 5). The outcome measures were death, reoperation, readmission within 90 days of transplantation, intensive care unit length of stay (LOS), hospital LOS, and packed red blood cell requirement in 48 hours. The 5 risk score groups with patients were similar in demographics and calculated MELD scores. The outcome measures in high-risk groups were similar to those in the lowest-risk group (score = 0). In the Cox regression model for LOS and survival, the composite risk score was not associated with poor survival or prolonged LOS (>3 weeks). Kaplan-Meier survival curves with log rank testing failed to show any difference in survival among different risk groups. In conclusion, patients with multiple risk factors for poor surgical outcomes can undergo successful transplantation with perioperative outcome and mortality comparable to those of low-risk patients. Liver Transpl 15: 1519–1524, 2009. © 2009 AASLD.

HBL and HCC are the most common hepatic malignancies in children. The role of OLT in children with HCC is still a matter of debate. The aim of this study was to review our experience of OLT for HCC. Medical records of patients (< 18 yr) who underwent OLT for HCC were reviewed and compared to children who underwent OLT for HBL and for indications other than malignancy. There were 25 patients: HCC (10 cases) and HBL (15 cases). The actuarial patient survival for HCC at one and five yr was 100% and 83.3%, for the HBL group the survival was 86.7% at both one and five yr, and for indications (n = 377) other than malignancy the patient survival for pediatric OLT at our center was 87.7% and 84.7% at one and five yr, respectively. The actuarial recurrence free survival at five yr was 83.3% for HCC and 66.8% for HBL. In conclusion, OLT is a good therapeutic modality for children with HCC and HBL.

Published data are limited describing renal outcomes in orthotopic liver transplant (OLT) recipients prescribed sirolimus (SRL) maintenance immunosuppression (MIS) and rabbit antithymocyte globulin (rATG) induction. We investigated whether SRL MIS and rATG induction facilitated recovery of acute kidney injury in the early postoperative period. This retrospective descriptive study screened 308 consecutive OLTs performed between 2006 and 2009. All patients received rATG induction with steroid avoidance. MIS consisted of SRL or TAC with mycophenolate mofetil. A total of 197 patients were included: 168 (85%) received TAC and 29 (15%) received SRL for a median of 365 days. Demographics were similar between groups except for a higher incidence of pretransplant renal dysfunction in the SRL recipients (SRL 59% versus TAC 21%;P<0.05). The eGFR was significantly (P<0.05) higher for all time points in the TAC group with the exception of month 2. However, improvement in eGFR was significantly (P<0.05) greater in the SRL group postoperatively. Our study suggests that rATG induction and SRL maintenance immunosuppression facilitate renal recovery for liver transplant recipients that develop acute kidney injury in the early postoperative period.

Propionic acidemia is a rare metabolic disorder that often results in episodic hyperammonemia, basal ganglia infarction, mental retardation, and cardiomyopathy. OLT has been used as a treatment for propionic acidemia, but its benefit in patients with this disease is unclear. The current study was undertaken to clarify the role of OLT in the management of this disease. The medical literature, a national registry of US OLT recipients, and a single institution liver transplant experience were reviewed for cases of OLT for propionic acidemia. Accumulated cases demonstrate that OLT has resulted in clear evidence of clinical improvement in several patients, often obviating the need for dietary restriction or other forms of medical management. OLT appears to halt the decline in neurocognitive function often associated with propionic acidemia. In total, 12 patients with propionic acidemia have undergone a total of 14 OLTs. A quantitative analysis of outcomes shows an overall patient survival rate of 72.2% at one year after OLT. In conclusion, OLT should be considered a treatment option for patients with propionic acidemia who continue to experience episodes of hyperammonemia in spite of maximal medical therapy. Early OLT may limit the development of mental retardation and/or cardiomyopathy.

Background. Pancreatic islet transplantation (PIT) has proven effective in achieving insulin independence, but to date, the impact of PIT on health-related quality of life (HRQL) has not been studied. Methods. Ten patients who have undergone PIT at our institution were administered three HRQL questionnaires: the Hypoglycemia Fear Survey, the 36-Item Short Form Health Survey (SF-36), and a fatigue questionnaire. HRQL was assessed before PIT, then 3, 6, and 12 months after PIT. Responses were compared by analysis of variance and paired Student’s t tests. Results. Hypoglycemia Fear Survey responses demonstrated that hypoglycemia-related anxiety and hypoglycemia-related behavior modification occurred less frequently after PIT (P=0.003 and 0.0001, respectively). The total scores of the hypoglycemia questionnaire were also significantly improved after PIT, from a median score of 156 points before transplantation to 55 points 3 months after PIT (P=0.004), 38 points 6 months after PIT (P=0.001), and 69 points 12 months after PIT (P=0.04). The median scores of all SF-36 components also improved after PIT. No significant changes were seen in the fatigue symptoms as assessed by the fatigue questionnaire. Conclusion. PIT recipients have less anxiety about the symptoms and consequences of hypoglycemia. PIT recipients also indicate that their behavior requires significantly less modification to prevent or treat hypoglycemia after PIT compared with before PIT. Further investigation is needed to determine whether PIT improves generic measures of HRQL.

Severe cholestasis after liver transplant is common. In this study, our aim was to develop an algorithm to guide biliary intervention in these patients.A retrospective review was performed on patients who had undergone a hepatobiliary scan, with or without subsequent endoscopic retrograde cholangiogram, during the immediate postoperative period. These findings were evaluated along with laboratory values to determine the benefit for this evaluative process. Biliary duct obstruction was defined asthan a 50% reduction in serum bilirubin within 48 hours of endoscopic retrograde cholangiogram intervention.Twelve patients had endoscopic retrograde cholangiogram with 6 stents in 25 patients with normal a hepatobiliary scan, and 2 patients met criteria for biliary duct obstruction. Twenty-two patients had endoscopic retrograde cholangiogram with 14 stents in 32 patients with delayed uptake, suggesting hepatocellular dysfunction on a hepatobiliary scan, and 4 patients met criteria for biliary duct obstruction. In the 57 patients with severe hyperbilirubinemia, 6 patients (11%) had biliary duct obstruction as a cause. Among the 34 endoscopic retrograde cholangiograms performed, 17% had biliary obstruction. On multivariate analysis, patients having both serum aspartate transaminase concentrations1500 IU/L and serum total bilirubin levels257 μmol/L had an odds ratio of 25.1 for predicting biliary obstruction (95% CI: 6-37; P = .002).A hepatobiliary scan with a combination peak serum aspartate transaminase and peak serum total bilirubin levels offer a valuable tool to identify patients with hepatocellular dysfunction and can avoid endoscopic retrograde cholangiogram in the immediate posttransplant period.

Transplantation at the University of Tennessee Health Science Center in Memphis, which began at the William F. Bowld Hospital and transferred to Methodist University Hospital in 2004, includes pediatric transplantation at LeBonheur Children's Medical Center. The multidisciplinary institute is dedicated to the treatment of patients with end-stage liver and kidney disease and allows those patients access to the integrated expertise of transplant surgeons, hepatologists, and nephrologists. The current, and most successful, era for the program began in 2006, when a change in leadership and clinical vision led to a dramatic increase in clinical activity. These changes have included wider acceptance of potential recipients for liver transplantation and broader use of marginal donor allografts. Streamlined surgical techniques have decreased operative times and have limited blood product usage. Additionally, the program uses an innovative immunosuppression protocol with the world's largest reported series of steroid-free, rabbit anti-thymocyte globulin induction and delayed introduction of tacrolimus in an effort to limit adverse effects of immunosuppression. Such adverse effects may include: infections, post-transplant diabetes mellitus, bone disease, and accelerated fibrosis from recurrent HCV related to steroids and impaired renal function from tacrolimus. These changes have resulted in aggressive donor usage with low complication rates and excellent outcomes.

OBJECTIVES Organ donation after cardiac death remains an available resource to meet the demand for transplant. However, concern persists that outcomes associated with donation after cardiac death liver allografts are not equivalent to those obtained with organ donation after brain death. The aim of this matched case control study was to determine if outcomes of liver transplants with donation after cardiac death donors is equivalent to outcomes with donation after brain death donors by controlling for careful donor and recipient selection, surgical technique, and preservation solution. MATERIALS AND METHODS A retrospective, matched case control study of adult liver transplant recipients at the University of Tennessee/Methodist University Hospital Transplant Institute, Memphis, Tennessee was performed. Thirty-eight donation after cardiac death recipients were matched 1:2, with 76 donation after brain death recipients by recipient age, recipient laboratory Model for End Stage Liver Disease score, and donor age to form the 2 groups. A comprehensive approach that controlled for careful donor and recipient matching, surgical technique, and preservation solution was used to minimize warm ischemia time, cold ischemia time, and ischemia-reperfusion injury. RESULTS Patient and graft survival rates were similar in both groups at 1 and 3 years (P = .444 and P = .295). There was no statistically significant difference in primary nonfunction, vascular complications, or biliary complications. In particular, there was no statistically significant difference in ischemic-type diffuse intrahepatic strictures (P = .107). CONCLUSIONS These findings provide further evidence that excellent patient and graft survival rates expected with liver transplants using organ donation after brain death donors can be achieved with organ donation after cardiac death donors without statistically higher rates of morbidity or mortality when a comprehensive approach that controls for careful donor and recipient matching, surgical technique, and preservation solution is used.

In the last 50 years of liver transplantation there has been significant improvement in all aspects of the operation, and it has become the standard of care in the treatment of end stage liver disease. Perioperative hemodynamic monitoring during the transplant operation is critical and currently the pulmonary artery catheter (PAC) remains the gold standard for cardiovascular monitoring. Transesophageal echocardiography (TEE), with the ability to visualize cardiac function and provide real-time feedback on the adequacy of intervention has had an increasing use in liver transplantation. The primary advantage of TEE is the ability to visualize cardiac function. Disadvantages of TEE include instrumentation cost, operator use, and familiarity with the information provided by the TEE. TEE provides a useful adjunct to PAC in intraoperative hemodynamic monitoring during liver transplantation, especially in those patients at risk for cardiac complications due to pre-existing cardiovascular disease.

Post-transplant, nonalcoholic hepatic steatosis and steatohepatitis are increasingly recognized as a complication of liver transplantation, and the progression of the latter through fibrosis to cirrhosis has been clearly shown. Non-alcoholic steatohepatitis (NASH) is independently associated with an increased risk of death from cardiovascular and liver diseases. While optimal therapy is not yet available in the post-liver transplant setting, knowledge gained in the therapy of NASH in the non-transplant setting can be used to design therapeutic interventions. In addition, early recognition with protocol liver biopsies and an effective preventive strategy by modifying known risk factors implicated in the recurrence of NASH would be the most effective way to curtail the progression of NASH before an effective treatment can be found. Additional rigorous research aimed at elucidating the pathogenesis, natural history, and selection of immunosuppressants for NASH is clearly warranted.

BACKGROUND: Spontaneous liver rupture is a rare occurrence during pregnancy. CASE: A young woman presented early in her pregnancy with severe abdominal pain, tachycardia, and hypotension. She was taken emergently to the operating room with a presumed diagnosis of ruptured ectopic pregnancy. Exploration revealed that her hemoperitoneum resulted from large fractures within her liver. During her resuscitation and treatment, a transvaginal ultrasound scan revealed a hydatidiform molar pregnancy. On resolution of postoperative complications and complete recovery, the patient was discharged home. CONCLUSION: This case illustrates that, although very unusual, hydatidiform molar pregnancies should be considered as a precipitating factor for spontaneous liver rupture.

Obesity, diabetes, and prior abdominal surgery are generally considered to increase the risk of liver transplantation. The aim of the present study was to define the effects of these factors on the immediate outcome after transplantation. Two hundred twenty-one consecutive liver transplants were analyzed. Twenty-eight patients were excluded. In the remaining 193 patients [mean age = 52 +/- 19 years, body mass index (BMI) = 28.5, Model for End-Stage Liver Disease (MELD) score at listing = 18.7], the risk from obesity was graded as follows: (0) BMIor = 30, (1) BMI = 30-34.9, (2) BMI = 35-39.9, and (3) BMIor =40. The presence of diabetes and prior abdominal surgery were each given 1 point. All the individual scores for obesity, diabetes, and prior surgery were added to produce a composite risk score for each patient. Patients were categorized into 6 risk groups, group 0 having the least risk and group 5 having the highest risk (none of the patients were in group 5). The outcome measures were death, reoperation, readmission within 90 days of transplantation, intensive care unit length of stay (LOS), hospital LOS, and packed red blood cell requirement in 48 hours. The 5 risk score groups with patients were similar in demographics and calculated MELD scores. The outcome measures in high-risk groups were similar to those in the lowest-risk group (score = 0). In the Cox regression model for LOS and survival, the composite risk score was not associated with poor survival or prolonged LOS (3 weeks). Kaplan-Meier survival curves with log rank testing failed to show any difference in survival among different risk groups. In conclusion, patients with multiple risk factors for poor surgical outcomes can undergo successful transplantation with perioperative outcome and mortality comparable to those of low-risk patients.

HBL and HCC are the most common hepatic malignancies in children. The role of OLT in children with HCC is still a matter of debate. The aim of this study was to review our experience of OLT for HCC. Medical records of patients (18 yr) who underwent OLT for HCC were reviewed and compared to children who underwent OLT for HBL and for indications other than malignancy. There were 25 patients: HCC (10 cases) and HBL (15 cases). The actuarial patient survival for HCC at one and five yr was 100% and 83.3%, for the HBL group the survival was 86.7% at both one and five yr, and for indications (n=377) other than malignancy the patient survival for pediatric OLT at our center was 87.7% and 84.7% at one and five yr, respectively. The actuarial recurrence free survival at five yr was 83.3% for HCC and 66.8% for HBL. In conclusion, OLT is a good therapeutic modality for children with HCC and HBL.

sedation assistants for deep sedation during ERCP without increasing the risk of adverse events of deep sedation. Su1590 Role of the Direct PerOral Cholangioscopy Using an Ultra-Slim Endoscope After Endoscopic Extraction of Choledocholithiasis for Detecting Small Bile Duct Lesions Obscure in Conventional Imagings Hyun Jong Choi*, Jong Ho Moon, Yun Nah Lee, Hee Kyung Kim, Hyeon Jeong Goong, Moon Han Choi, Tae Hoon Lee, Sang-Woo Cha, Young Deok Cho, Sang-Heum Park Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea (the Republic of); Department of Pathology, SoonChunHyang University School of Medicine, Bucheon, Korea (the Republic of) Background: Direct peroral cholangioscopy (POC) using an ultra-slim upper endoscope can provide high-resolutional endoscopic images of the bile duct. Therefore, direct POC may detect obscure bile duct lesions in preceding imaging modalities including computed tomography, magnetic resonance cholangiopancreatography, and endoscopic retrograde cholangiopancreatography. The aim of this study was to evaluate the usefullness of direct POC using an ultra-slim upper endoscope after endoscopic extraction of choledocholithiais. Methods: Total 207 patients have undergone direct POC to evaluate bile duct clearance after endoscopic extraction of choledocholithiasis. All included patients had dilated extrahepatic bile duct more than 10 mm and were undergone endoscopic sphincteroplasty before POC. Patients with defined bile duct lesions in preceding imaging modalities were excluded in this study. Direct POC was performed by using an ultra-slim (! 5.5 mm in outer diameter of distal end) upper endoscopes. Abnormal POC findings were evaluated by using narrow band imaging and forceps biopsy under endoscopic guidance, if possible. Results: Direct POC was successful in 199 patients (96.1%). Abnormal intraductal lesions were detected in 31 patients (15.6%) including 3 villous mucosal lesions, 2 papillary mucosal lesions, 14 polypoid mucosal lesions and 11 nonspecific inflammatory lesions. POC-guided forceps biopsy was successful in 28/31 patients (90.3%) with tissue adequacy for the histologic evaluation in 24/31 (77.4%). Final diagnosis by histopathologic evaluation of abnormal bile duct lesions were 4 cholangiocarcinomas, 2 intraductal papillary neoplasms in the bile duct with dysplasia, 1 bile duct adenoma with dysplasia, and 24 nonspecific inflammatory lesions. Residual stones were detected in 25 patients (14.5%) and extracted under direct POC (92%, 23/25). Cholangitis conservatively managed was occurred in one patient (0.5%, 1/ 207) after direct POC. No other significant direct POC-related adverse events were occurred. Conclusion: Endoscopic evaluation with direct POC using an ultra-slim upper endoscope after endoscopic extraction of choledocholithiasis can be helpful to detect small bile duct lesions including cholangiocarcinoma that were obscure or overlooking in preceding imaging modalities. Su1591 Magnetic Resonance Cholangio-Pancreatography (MRCP) Has Low Sensitivity in Diagnosing Biliary Strictures After Liver Transplantation: a Single Tertiary Care Center Experience Ali Akbar*, Satheesh P. Nair, Mohammad K. Ismail, Muhammad Bilal, Jason Vanatta, James D. Eason, Salil Parikh, Sanjaya K. Satapathy Gastroenterology and Hepatology, University of Tennesse, Germantown, TN; Transplant surgery, University of Tennessee, Memphis, TN; Radiology, Methodist University Hospital, Memphis, TN Aim: Biliary strictures are common complication after liver transplantation (LT). We aimed to determine the accuracy of MRCP in diagnosing biliary strictures (BS) in liver transplant recipients (LTRs) when compared to direct cholangiographic methods (Endoscopic retrograde cholangio pancreatography (ERCP) and/or percutaneous transhepatic cholangiography (PTC). Setting: Tertiary care medical center performing O100 LT a year. Methods: Retrospective chart review of LTRs from 7/2008 until 4/2014 was performed. Those who had MRCP performed for suspected BS followed by ERCP or PTC within 4 weeks were included. BS on ERCP/ PTC without prior MRCP and those who underwent surgery or followed clinically after an MRCP were excluded. A cholangiographic narrowing (on ERCP/PTC) that required balloon dilation and/or stent placement was considered a biliary stricture and was considered clinically significant if the intervention resulted in atleast 30% improvement of bilirubin (bili) and/or alkaline phosphatase (AP) within 2 weeks. Data collected include LT indication, biliary anastomosis type, Pre-MRCP bili and AP, anastomotic vs non anastomotic BS, Immunosuppression at the time of MRCP, time intervals between LT & MRCP as well as between MRCP & ERCP/PTC. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of MRCP in diagnosing biliary strictures (with known ERCP/PTC findings) were calculated. Results: After review of 679 LTRs a total of 32 patients (18 males 54.5%, median age 52.6 8.8 years) were included. All had an MRCP followed by either ERCP or PTC within 4 weeks. HCV related end stage liver disease was the most common indication for LT (19/32 59.4%). Median LT to MRCP time was 387 (35-2285) days. Biliary anastoAB342 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 5S : 2015 mosis was duct to duct in all except one who had hepatico-jejunostomy. Pre-MRCP bili (8.7 8.3mg/dl) and AP (657 525 unit/L) were elevated. 27 patients (84.3%) were on tacrolimus, 13 (39.4%) on mycophenolate, 7 (21.2%) on rapamycin, 2 (6.1%) on everolimus and 1 (3%) on cyclosporine at the time of MRCP. MRCP showed anastomotic BS in 14 of 32 patients. ERCP and PTC subsequently revealed a total of 21 BS (ERCP 15, PTC 6; 20 anastomotic and 1 non-anastomotic). This included all 14 seen on MRCP (PPV of 100%). Remaining 7 BS (6-anastomotic and 1 non-anastomotic), diagnosed on ERCP (5) and PTC (2), were not detected on earlier MRCP (Sensitivity 66.7%-cholangiographic BS). However only 4 of those 7 were clinically significant (Sensitivity 77.8%). 11 LTRs had no BS on either modality (Specificity of MRCP 100%). NPV of MRCP was noted to be 61.1% for cholangiographic BS (77.8% for clinically significant BS). Conclusion: Despite excellent specificity, MRCP may not show all biliary strictures in liver transplant recipients and hence, we recommend further direct cholangiographic evaluation in appropriate clinical settings. Baseline characteristics and Results Total Patients 32 Sex (male/female) 18/14 Age (years, median SD) 52.6 8.8 Reason for transplantation (n, %) HCV Cirrhosis 19 (59.3%) HBV Cirrhosis 1 (3.1%) Alcoholic Cirrhosis 3 (9.3%) Non alcoholic steatohepatitis Cirrhosis 3 (9.3%) PBC 1 (3.1%) Sarcoidosis 1 (3.1%) Othersy 4 (12.5%) Immunosuppression at MRCP (n, %) Tacrolimus 27 (84.3%) Mycophenolic acid 13 (40.6%) Everolimus / Cyclosporine 2 (6.2%) / 1 (3.1%) Rapamune 7 (21.8%) Type of Biliary anastomosis duct-duct / bilio-digestive 31 / 1 Time from transplantation to MRCP, days (median SD) 387 35-2285 Time from MRCP to ERCP/PTC ! 4 weeks in all 32

Bedside pleurodesis through a tube thoracostomy has been shown to be effective treatment of malignant pleural effusion and pneumothorax with persistent air leak. A variety of agents can be used, and each has been shown to produce rare but potentially serious complications. We report a case of sudden, severe respiratory failure in a 42-year-old man after pleurodesis with 300 mg of doxycycline. His response was consistent with an anaphylactic reaction. After intubation, mechanical ventilation and nebulizer treatments, he rapidly recovered to baseline. On the basis of this report and a review of the literature, we believe that doxycycline may not be an innocuous agent for bedside pleurodesis and that such procedures warrant a monitored setting.

Foregut cystic developmental malformations are rare developmental anomalies. The problems inherent to these malformations are their presentation across specialties that include embryology, anatomy, pathology, thoracic foregut surgery, pediatric surgery and general abdominal surgery. The direct consequence of this variation has resulted in diverse terminology, classification and a failure to identify the correlation. The article aims to summarize and unify the embryological concepts of foregut cystic malformation, to suggest a generic title to the various groups of these interrelated disorders and a uniform use of nomenclature on the basis of unifying concepts of embryopathogeneis.