and 2 Multi-Organ Transplant Institute, Ochsner Clinic Foundation, New Orleans, LA Liver transplantation (LT) with donation after circulatory death (DCD) donors has been associated with a high rate of ischemic-type biliary strictures (ITBSs) and inferior graft survival. To investigate the impact of an intraoperative tissue plasminogen activator (tPA) on outcomes following DCD LT, we conducted a retrospective analysis of DCD LT at the Toronto General Hospital (TGH) and the Ochsner Medical Center (OMC). Between 2009 and 2013, 85 DCD LTs were performed with an intraoperative tPA injection (n 5 30 at TGH, n 5 55 at OMC), and they were compared with 33 DCD LTs without a tPA. Donor and recipient characteristics were similar in the 2 groups. There was no significant difference in the intraoperative packed red blood cell transfusion requirement (3.2 6 3.4 versus 3.1 6 2.3 U, P 5 0.74). Overall, biliary strictures occurred less commonly in the tPA-treated group (16.5% versus 33.3%, P 5 0.07) with a much lower rate of diffuse intrahepatic strictures (3.5% versus 21.2%, P 5 0.005). After 1 and 3 years, the tPA group versus the non-tPA group had superior patient survival (97.6% versus 87.0% and 92.7% versus 79.7%, P 5 0.016) and graft survival (96.4% versus 69.7% and 90.2% versus 63.6%, P < 0.001). In conclusion, a tPA injection into the hepatic artery during DCD LT reduces ITBSs and improves graft and patient survival without increasing the risk for bleeding. Liver Transpl 21:321-328, 2015. The use of liver transplantation (LT) as a lifesaving treatment for patients with end-stage liver disease continues to be primarily limited by donor organ availability. Donation after circulatory death (DCD) donors represent an important potential source to expand the donor pool for LT. However, posttransplant outcomes following DCD LT have to date been inferior in comparison with outcomes following LT with donation after brain death (DBD) donors. [1][2][3][4][5][6][7][8] Despite an increased use of DCD livers in the early part of the past decade, utilization has decreased in recent years as a result of inferior outcomes. 9 Biliary complications are the main contributor to inferior outcomes in DCD LT, with reported biliary stricture rates between 30% and 50% (more than double the rate for LT from DBD donors). The higher rate
Donation after circulatory death (DCD) liver transplantation (LT) reportedly yields inferior survival and increased complication rates compared with donation after brain death (DBD). We compare 100 consecutive DCD LT using a protocol that includes thrombolytic therapy (late DCD group) to an historical DCD group (early DCD group n = 38) and a cohort of DBD LT recipients (DBD group n = 435). Late DCD LT recipients had better 1- and 3-year graft survival rates than early DCD LT recipients (92% vs. 76.3%, p = 0.03 and 91.4% vs. 73.7%, p = 0.01). Late DCD graft survival rates were comparable to those of the DBD group (92% vs. 93.3%, p = 0.24 and 91.4% vs. 88.2%, p = 0.62). Re-transplantation occurred in 18.4% versus 1% for the early and late DCD groups, respectively (p = 0.001). Patient survival was similar in all three groups. Ischemic-type biliary lesions (ITBL) occurred in 5%, 3%, and 0.2% for early DCD, late DCD, and DBD groups, respectively, but unlike in the early DCD group, in the late DCD group ITBL was endoscopically managed and resolved in each case. Using a protocol that includes a thrombolytic therapy, DCD LT yielded patient and graft survival rates comparable to DBD LT.
Liver transplantation (LT) using allografts from hepatitis C virus (HCV)-viremic/nucleic acid testing-positive donors' (DNAT+) organs into HCV-aviremic recipients (rHCV−) has been limited owing to nearly universal HCV transmission and concerns regarding availability, safety, and efficacy post-LT with direct-acting antiviral (DAA) therapy. We report our experience of LT using DNAT+ organs into rHCV− as a routine standard of care. Following verification of DAA access, absence of critical drug-drug interactions (DDIs) with DAAs, and informed consent, allocated DNAT+ organs were offered to patients on the waiting list for LT irrespective of recipient HCV status. Between June 2018 and December 2019, 292/339 rHCV− received an LT. Forty-seven patients were excluded from analysis because of recipient HCV viremia, refusal to receive DNAT+ organs, or inability to receive DAA therapy post-LT. Of these 292 patients, 61 rHCV− received DNAT+ livers (study group), and 231 rHCV− received DNAT− (aviremic donors [nuclear acid test-negative donors]) livers (control group). Recipient and donor characteristics as well as 1-year post-LT patient and graft survival were similar between groups. In the study group, 4 patients died, and 1 patient required retransplantation within the first year post-LT (all unrelated to HCV); 56 patients received DAA therapy, with a median time from LT to the start of DAA treatment of 66.9 days (interquartile range [IQR], 36-68.5), and 51 patients completed DAA treatment, all achieving sustained virologic response for 12 or more weeks (SVR-12) (1 patient required retreatment owing to relapse following initial DAA therapy). No patients had evidence of fibrosing cholestatic hepatitis or extrahepatic manifestations of HCV. This report indicates that transplantation of DNAT+ livers into rHCV− and subsequent DAA therapy is associated with clinical outcomes comparable to those achieved with DNAT− allografts.
Progressive familial intrahepatic cholestasis (PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described.
Older donor age does not preclude excellent results from living-donor kidney transplantation but should be appreciated as being associated with relatively lower GFR.
The use of livers from hepatitis B surface antigen-negative (HBsAg 2 )/hepatitis B core antibody-positive (HBcAb 1 ) donors in liver transplantation (LT) for HBsAg 2 /HBcAb 2 recipients is still controversial because of a lack of standard antiviral prophylaxis and long-term follow-up. We present our 13-year experience with the use of HBcAb 1 donor livers in HBcAb 2 recipients. Patients received prophylaxis with hepatitis B immunoglobulin at the time of LT and then lamivudine daily. De novo hepatitis B virus (HBV) was defined as positive HBV DNA detection. Between January 1999 and December 2010, 1013 adult LT procedures were performed at our center. Sixty-four HBsAg 2 /HBcAb 2 patients (6.3%) received an HBsAg 2 /HBcAb 1 liver. All donor sera were negative for HBcAb immunoglobulin M and HBV DNA. The mean follow-up was 48.8 6 40.1 months (range 5 1.2-148.8). Both the patient survival rates and the graft survival rates were 92.2% and 69.2% at 1 and 5 years, respectively. No graft losses or deaths were related to de novo HBV. Nine of the 64 patients (14.1%) developed de novo HBV. The mean time from LT to de novo HBV was 21.4 6 26.1 months (range 5 10.8-92.8 months). De novo HBV was successfully treated with adefovir or tenofovir. In conclusion, HBcAb 1 allografts can be safely used in HBcAb 2 recipients without increased mortality or graft loss. Lifelong prophylaxis, continuous surveillance, and compliance are imperative for success. Should a de novo infection occur, our experience suggests that a variety of treatments can be employed to salvage the graft and obtain serum HBV DNA clearance. Liver Transpl 19:611-618, 2013. V C 2013 AASLD.Received November 11, 2012; accepted March 2, 2013.The disparity between the liver allograft supply and the demand remains a problem for those caring for patients with end-stage liver disease who require liver transplantation (LT). 1 In response, several strategies, including the use of hepatitis B surface antigen-negative (HBsAg 2 )/hepatitis B core antibody-positive (HBcAb 1 ) donors, have been used to expand the liver donor pool. This practice varies with the regional incidence of hepatitis B virus (HBV), and such donors represent 3% to 6% of the donor pool in the United States, 8% to 15% of the donor pool in Europe, and 50% to 55% of the donor pool in Asia. [2][3][4][5] The presence of persistent intrahepatic HBV covalently closed circular DNA in HBcAb 1 patients has been reported after HBsAg clearance, and constitutes a potential reservoir for viral reactivation. 6,7 In the absence of prophylaxis, the rate of de novo HBV has reached up to 75% to 80% in HBsAg 2 /HBcAb 2 recipients, 15% to 20% in HBcAb 1 or HBsAg 1 recipients, and 5% to 10% in HBcAb 1 /hepatitis B surface antibody-positive (HBsAb 1 ) recipients. 8 There is a consensus that HBsAg 2 /HBcAb 1 donor livers should be preferentially used in recipients with a diagnosis of HBV because these patients require HBV treatment
Purpose To assess response to transcatheter arterial chemoembolization (TACE) based on immune markers and tumor biology in patients with hepatocellular carcinoma (HCC) who were bridged to liver transplantation, and to produce an optimized pretransplantation model for posttransplantation recurrence risk. Materials and Methods In this institutional review board-approved HIPAA-compliant retrospective analysis, 93 consecutive patients (73 male, 20 female; mean age, 59.6 years; age range, 23-72 years) underwent TACE with doxorubicin-eluting microspheres (DEB) (hereafter, DEB-TACE) and subsequently underwent transplantation over a 5-year period from July 7, 2011, to May 16, 2016. DEB-TACE response was based on modified Response Evaluation Criteria in Solid Tumors. Imaging responses and posttransplantation recurrence were compared with demographics, liver function, basic immune markers, treatment dose, and tumor morphology. Treatment response and recurrence were analyzed with uni- and multivariate statistics, as well as internal validation and propensity score matching of factors known to affect recurrence to assess independent effects of DEB-TACE response on recurrence. Results Low-grade tumors (grade 0, 1, or 2) demonstrated a favorable long-term treatment response in 87% of patients (complete response, 49%; partial response, 38%; stable disease [SD] or local disease progression [DP], 13%) versus 33% of high-grade tumors (grade 3 or 4) (complete response, 0%; partial response, 33%; SD or DP, 67%) (P < .001). Of the 93 patients who underwent treatment, 82 were followed-up after transplantation (mean duration, 757 days). Recurrence occurred in seven (9%) patients (mean time after transplantation, 635 days). Poor response to DEB-TACE (SD or DP) was present in 86% of cases and accounted for 35% of all patients with SD or DP (P < .001). By using only variables routinely available prior to liver transplantation, a validated model of posttransplantation recurrence risk was produced with a concordance statistic of 0.83. The validated model shows sensitivity of 83.6%, specificity of 82.6%, and negative predictive value of 98.4%, which are pessimistic estimates. Conclusion Response to DEB-TACE is correlated with tumor biology and patients at risk for posttransplantation recurrence, and it may be associated with HCC recurrence after liver transplantation. RSNA, 2017 Online supplemental material is available for this article.
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