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Background Microvascular hepatic artery reconstruction (MHAR) is associated with decreased rates of hepatic artery thrombosis (HAT) in living donor liver transplantation (LDLT). There is a paucity of literature describing the learning points and initiation of this technique at the institutional level. The objective of this study is to report our institutional experience using MHAR in adult LDLT with a focus on technique and outcomes. Methods A retrospective review of adult patients who underwent LDLT from January 2012 to December 2020 was conducted. Patients were divided into two groups, those who underwent LDLT without MHAR and with MHAR. We analyzed cases for technical data including donor and recipient artery characteristics, anastomotic techniques, intraop events, and postop complications. A Mann–Whitney test was performed to compare outcomes between non-MHAR and MHAR patients. Results Fifty non-MHAR and 50 MHAR patients met inclusion criteria. Median age at transplantation was 58 (interquartile range [IQR] 11.8) and 57.5 years (IQR 14.5), respectively. Median follow-up for MHAR patients was 12.8 months (IQR 11.6). The most common recipient arteries were the right hepatic artery (HA) (58%) and left HA (20%). Median size of recipient and donor arteries were 3.3 mm (IQR 0.7) and 3.1 mm (IQR 0.7), resulting in a median mismatch size of 0.3 mm (IQR 0.4). Median microanastomosis time was 44 minutes (IQR 0). HAT, graft failure, and mortality rates were higher in the non-MHAR cohort (6% vs. 0%, 8% vs. 0%, and 16% vs. 6%, respectively); however, these did not reach statistical significance. Conclusion This study found lower rates of HAT and graft failure after implementing MHAR, though statistical significance was not achieved. Larger cohort studies are needed to further assess the potential benefit of MHAR in adult LDLT. From our experience, MHAR requires cooperation between the transplant and microsurgical teams, with technical challenges overcome with appropriate instrumentation and planning.

(COVID-19) has resulted in significant morbidity and mortality in solid organ transplant recipients. In December 2020, at the peak of the Los Angeles outbreak, our center rapidly implemented a protocol to improve outpatient management and provide bamlanivimab or casirivimab-imdevimab [COVID monoclonal antibody (mAb) therapies] to all eligible COVID-19 positive liver and kidney transplant recipients.A retrospective review of all abdominal organ transplant recipients who were COVID-19 polymerase chain reaction positive between February 2020 and February 2021 from our center was performed. Patient demographics, COVID-19 treatments, hospitalizations, and survival were reviewed. Patients were considered eligible for COVID mAb therapy if they met outpatient criteria at the time of diagnosis.In the study period, 121 patients in the kidney transplant recipients group (KG) and 105 patients in the liver or combined liver/kidney transplant recipients group (LG) were COVID-19 polymerase chain reaction positive. Hospitalization rates were similar for the KG (45%) versus LG (35%) (P = 0.20), but mortality was higher for the KG (22%) when compared to LG (10%) (P = 0.02). Our programmatic response, including outpatient COVID mAb therapies, reduced hospitalizations (P = 0.01) and deaths (P = 0.01). Ninety-four KG and 87 LG patients were identified as potentially eligible for COVID mAb therapy, and 17 KG and 17 LG patients were treated. COVID mAb therapies reduced hospitalization from 32% to 15% (P = 0.045) and eliminated mortality (13% versus 0%, P = 0.04).An aggressive approach including outpatient COVID mAb therapy in the COVID positive abdominal organ transplant recipients significantly decreased hospitalization and death. Early outpatient intervention for COVID-19 disease in transplant patients should be considered where possible.

PURPOSE OF REVIEW Recently the United Network for Organ Sharing (UNOS) adopted new rules for the allocation of liver allografts for recipients with hepatocellular carcinoma (HCC) in hopes of removing regional variation in HCC practice and regional differences in patient survival. Understanding how previous changes to HCC allocation have both succeeded and failed to match the pretransplant mortality of HCC and non-HCC patients on the waitlist will help us to better evaluate these changes and predict where we may again fail. RECENT FINDINGS Previous revisions of the HCC allocation rules were successful in more accurately matching the waitlist mortality of HCC and non-HCC patients. Efforts to select for less aggressive tumor biology have resulted in better disease free and patient survival. Several articles have also supported the practice of using locoregional therapies to downstage the patients to within Milan criteria. New rules seek to reduce the amount of geographic disparity in the allocation system. SUMMARY Over time UNOS has steady improved the liver allocation polices to attempt to match pretransplant mortality for patients with HCC and without HCC. The latest changes to the organ allocation rules succeed in implementing some of these best practices. However, one can also predict several ongoing challenges to fair allocation that may not have been addressed by recent changes.

Liver transplantation presents unique challenges in patients who do not accept blood transfusions. The difficulty of balancing chemical augmentation and handling the technical difficulty of the surgery make transfusion-free liver transplantation an exception rather than the norm. However, at our center, we have performed 27 successful living donor liver transplants in transfusion-free patients. We describe a case of hepatic artery thrombosis (HAT) after living donor liver transplantation requiring retransplantation. This first report of safe retransplantation without blood products demonstrates that even graft-threatening complications can be safely managed in a transfusion-free setting. However, it remains unclear if the medical augmentation to meet hematologic and coagulation parameters before transfusion-free transplantation may increase the risk of postoperative HAT and other thrombotic complications. Although it is our center’s experience that the thrombosis rate is comparable with the published rate in standard transfusion-eligible living donor liver transplantations and this case demonstrates that HAT can be safely managed in this setting, further study on the risks and benefits of hematopoietic stimulants as pretransplant optimization is warranted.

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81-0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R2 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.

Background Biliary complications in liver transplantation (LT) can cause significant morbidity or even lead to a potential graft loss and patient mortality. Oftentimes biliary internal stents (ISs) are used at the time of LT to lower the risk for or prevent these biliary complications; however, their efficacy and outcomes remain controversial. Methods A retrospective cohort study was conducted on all of the adult patients who underwent a deceased-donor LT (DDLT) with an end-to-end choledococholedocostomy. An IS was placed across the biliary anastomosis, passing through the ampulla. We compared the demographic profiles and various outcomes between the 2 groups (no-IS group vs IS group) and examined risk factors associated with anastomotic biliary complications. Results The study comprised 350 patients in the no-IS group and 132 patients in the IS group. Anastomotic biliary fistula (ABF) occurred in 5 (1.4%) and 1 (0.8%) patients in the no-IS group and the IS group, respectively (P = .55). Anastomotic biliary stricture (ABS) occurred in 53 (15.1%) and 18 (13.6%) patients, respectively (P = .68). No significant difference was found in the overall biliary complications between the 2 groups (P = .33). In multivariate logistic regression analysis, acute rejection was the only risk factor for ABS (P = .02). One biliary complication–induced mortality occurred in the no-IS group in which the patient died of an ABF-induced hepatic artery pseudoaneurysm rupture. Conclusion The use of biliary ISs in DDLT did not reduce the overall risk for biliary complications, but more research is needed to draw definite conclusions.

We report two cases of successful renal transplantation with allografts from donors who suffered anoxic brain injury as the primary cause of death from house fires. Each was treated prophylactically with hydroxocobalamin (Cyanokit) for suspected cyanide toxicity. During organ procurement, gross examination was notable for deep discoloration of the parenchymal tissues. Approximately 6 and 18 months after transplantation, both recipients have excellent renal graft function and remain independent from hemodialysis (HD). Hydroxocobalamin is the antidote for suspected acute cyanide toxicity. While largely tolerated by the recipient, there is concern over the potential functional implications of the associated side effects of dramatic tissue discoloration and development of oxalate crystals. Furthermore, difficulties performing hemodialysis in patients treated with hydroxocobalamin have been reported due to discoloration of the effluent fluid impacting the colorimetric sensor, causing false alarms and repetitive interruptions. As such, many transplant centers in the United States (US) continue to reject these organs. We seek to highlight two cases of successful transplantation following donor administration of hydroxocobalamin (Cyanokit) and present the first documented case of successful perioperative intermittent hemodialysis following transplantation of an allograft exposed to hydroxocobalamin. Furthermore, we emphasize the importance of optimal organ utilization and caution against unnecessary refusal.

HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4+ and CD8+ T cells able to produce IFN-gamma following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4+ and CD8+ effector/memory (CD45RC- CD62L-) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naïve (CD45RC+ CD62L+) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process.

Pancreatic islet transplantation is a minimally invasive procedure that can restore normoglycemia and insulin independence in Type 1 diabetics without the surgical complications associated with vascularized pancreas transplantation. The advances made in this field over the past decade have dramatically improved patient outcomes, and the procedure is now transitioning from an experimental treatment to a clinical reality. Nonetheless, a number of important issues continue to hamper the success of islet transplantation and must be addressed before there is widespread clinical acceptance. These include the relative inefficiency of the islet isolation process, the progressive loss of islet function over time and the need for multiple donors to achieve insulin independence. Here, we discuss the current status of islet transplantation and examine its future as a treatment for Type 1 diabetes.

Hypothesis Despite the overall acceptance of laparoscopic donor nephrectomy (LDNX), concern remains about the application of this technique in certain complex situations, such as right-sided nephrectomies and in donors with complex kidney anatomy and obese donors. This study was designed to determine if complication rates have remained stable as we have offered LDNX to all medically acceptable donors and to analyze the results of cases in each of the complex categories. We hypothesized that complication rates in the 3 complex categories would be equivalent to those among more straightforward cases. Design Retrospective medical record review. Setting Academic medical center. Patients A total of 1045 patients who underwent LDNX between November 3, 1999, and August 28, 2009. Main Outcomes Measures Operative times, lengths of hospital stay, overall complications, major complications, conversions to open surgery, blood transfusions, readmissions, and reoperations. Results The outcomes of the first 250 patients (when LDNX was selectively offered) were compared with the outcomes of the last 795 patients (when LDNX was offered to all medically acceptable donors). Overall operative times significantly improved (212 vs 176 minutes), overall complication rates did not change (6.4% vs 5.5%), and major complication rates significantly declined (4.0% vs 1.4%). Among the last 795 patients, 1 conversion to open surgery and 1 blood transfusion occurred. There were no deaths in the series. Moreover, no differences in overall or major complication rates were seen when cases involving 200 right-sided nephrectomies, 204 donors with complex kidney anatomy, and 148 obese donors were analyzed independently. Conclusions Low complication rates persist for LDNX, even when applied to more technically challenging cases. This procedure is offered to all medically acceptable donors, with an excellent safety profile, and should be considered the standard of care for kidney donation.

Adeno-associated virus encodes four nonstructural proteins, which are known as Rep78, Rep68, Rep52, and Rep40. Expression of these nonstructural proteins affects cell growth and gene expression through processes that have not yet been characterized. Using a yeast two-hybrid screen, we have demonstrated that a stable interaction occurs between the viral proteins Rep78 and Rep52 and the putative protein kinase PrKX, which is encoded on the X chromosome. The stability and specificity of the Rep-PrKX interaction were confirmed by coimmunoprecipitation of complexes assembled in vitro and in vivo. Overexpressed PrKX, which was purified from cos cells, was shown to phosphorylate a synthetic protein kinase A (PKA) substrate. However, this activity was dramatically inhibited by stoichiometric amounts of Rep52 and weakly inhibited with Rep68, which lacks the carboxy-terminal sequence contained in Rep52. Similarly, a stable interaction was observed with Rep78, which also contains the carboxy-terminal sequence of Rep52. A stable interaction and inhibition were also observed between Rep52 and the catalytic subunit of PKA. By using surface plasmon resonance and kinetic studies, Kis of approximately 300 and 167 nM were calculated for Rep52 with PKA and with PrKX, respectively. Thus, Rep52 but not Rep68 can significantly inhibit the trans- and autophosphorylation activities of these kinases. The biological effects of Rep78-specific inhibition of PKA-responsive genes are illustrated by the reduction of steady-state levels of cyclic AMP-responsive-element-binding protein and cyclin A protein.

We explored the tolerogenicity of liver allografts (Ltx) by characterizing the phenotype and persistence of alloreactive T cells after spontaneously tolerant Ltx in mice. Using adoptive transfer of TCR-tg direct and indirect donor-reactive T cells, we found that LTx (BALB→B10) induced a stronger CD4 T cell response than either skin or heart Tx. Moreover, large numbers of donor-reactive T cells persist 21 days after Ltx and do not upregulate Foxp3, even though tolerance to subsequent allospecific skin grafts is established. In vivo MLR confirmed the persistence of endogenous effector CD4 T cells at 21 and 250 days post-Ltx. Overall, these findings are consistent with an ongoing effector alloresponse rather than immune regulation after Ltx. In contrast, the CD8 donor-reactive T cells were significantly reduced, though still detectable, after Ltx. However, post-Ltx animals selectively eliminate allogenic target cells in an in vivo CTL assay. Thus, deletion of effector CD8 T cells may help protect liver allografts, but cannot completely account for Ltx tolerance. Finally, CD4, CD8, and Total T cells isolated from day 90 post-Ltx mice reject donor skin grafts when transferred into Rag1-/- hosts, indicating that Ltx tolerance cannot be transferred via the immune compartment. These data demonstrate the magnitude and persistence of the anti-donor T cell responses after Ltx and opposes either deletional tolerance or regulatory T cell induction as mechanisms for Ltx tolerance.