Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis c infected donors to hepatitis c naïve recipients: A large single center experience.

BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.

Novel NMP split liver model recapitulates human IRI and demonstrates ferroptosis modulators as a new therapeutic strategy.

BACKGROUND: Almost 9%of deceased donor livers are discarded as marginal donor livers (MDL) due to concern of severe ischemia reperfusion injury (IRI). Emerging data supports ferroptosis (iron regulated hepatocellular death) as an IRI driver, however lack of robust preclinical model limits therapeutic testing. In this manuscript we describe the development of a novel rigorous internal control system utilizing normothermic perfusion of split livers to test ferroptosis regulators modulating IRI. METHODS: Upon institutional approval, split human MDLs were placed on our normothermic perfusion machine, Perfusion Regulated Organ Therapeutics with Enhanced Controlled Testing (PROTECT), pumping arterial and portal blood. Experiment 1 compared right (UR) and left (UL) lobes to validate PROTECT. Experiment 2 assessed ferroptosis regulator Deferoxamine in Deferoxamine Agent Treated (DMAT) vs. No Agent Internal Control (NAIC) lobes. Liver serology, histology, and ferroptosis genes were assessed. RESULTS: Successful MDL perfusion validated PROTECT with no ALT or AST difference between UR and UL (∆ALT UR: 235, ∆ALT UL: 212; ∆AST UR: 576, ∆AST UL: 389). Liver injury markers increased in NAIC vs. DMAT (∆ALT NAIC: 586, ∆ALT DMAT: -405; ∆AST NAIC: 617, ∆AST DMAT: -380). UR and UL had similar expression of ferroptosis regulators RPL8,HO-1 and HIFα. Significantly decreased intrahepatic iron (p = .038), HO-1 and HIFα in DMAT (HO-1 NAIC: 6.93, HO-1 DMAT: 2.74; HIFαNAIC: 8.67, HIFαDMAT: 2.60)and no hepatocellular necrosis or immunohistochemical staining (Ki67/Cytokeratin-7) differences were noted. CONCLUSION: PROTECT demonstrates the therapeutic utility of a novel normothermic perfusion split liver system for drug discovery and rapid translatability of therapeutics, driving a paradigm change in organ recovery and transplant medicine. Our study using human livers, provides preliminary proof of concept for the novel role of ferroptosis regulators in driving IRI.

Kidney paired donation in developing countries: A global perspective.

Purpose of review: We review the key principles of kidney paired donation (KPD) and discuss the status and unique considerations for KPD in developing countries. Recent findings: Despite the advantages of KPD programs, they remain rare among developing nations, and the programs that exist have many differences with those of in developed countries. There is a paucity of literature and lack of published data on KPD from most of the developing nations. Expanding KPD programs may require the adoption of features and innovations of successful KPD programs. Cooperation with national and international societies should be encouraged to ensure endorsement and sharing of best practices. Summary: KPD is in the initial stages or has not yet started in the majority of the emerging nations. But the logistics and strategies required to implement KPD in developing nations differ from other parts of the world. By learning from the KPD experience in developing countries and adapting to their unique needs, it should be possible to expand access to KPD to allow more transplants to happen for patients in need world-wide.

Biliary Intraepithelial Neoplasia With Gallbladder Adenoma and Cirrhosis: A Case Report.

Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of cholangiocarcinoma that has been rarely reported. The present study reports a 56-year-old male with low-grade BilIN of the bile ducts and the cystic duct margin. Stent exchange endoscopy demonstrated an irregular, intraductal mass extending along the common bile duct, common hepatic duct, and hepatic duct bifurcation. The peribiliary mass was found to abut the right portal vein, inferior vena cava, and pancreatic head, and replaced the right hepatic artery. In addition, there was evidence of gallbladder adenoma managed with cholecystectomy and a right-lobed liver lesion and cirrhosis, which prompted the discussion of prophylactic liver transplantation. We emphasize the radiological features of BilIN and associated pathological findings through multiple imaging modalities. Consideration of this diagnosis is indicated in western countries and requires timely management based on available guidelines.

Kidney Autotransplantation for Treatment of Ureteric Obstruction: A Case Report and Brief Review of the Literature.

Autologous kidney transplantation is a relatively rare procedure that has been used as an alternative treatment for a variety of complex genitourinary problems, in particular for the treatment of complex proximal ureteral strictures. In this case report, a 47-year-old male, who had undergone a living donor nephrectomy 14 years earlier, presented with episodes of acute kidney injury on chronic kidney disease. He was found to have a complex proximal ureter stricture of his solitary right kidney. He underwent nephrectomy with subsequent autotransplantation of the kidney into the right iliac fossa. His renal function improved significantly after surgery. Renal autotransplantation may be considered for the management of proximal ureteral obstruction when alternative options are contraindicated.

Treatment of Hepatitis C Post-Liver Transplantation Could Mitigate Discard Rates of Hepatitis C-Positive Deceased Donor Livers and Expand the Donor Pool.

BACKGROUND: Prior to 2014, treatment for hepatitis C was limited. However, the subsequent introduction of direct acting antiviral medications (DAA) against hepatitis C led to improvements in morbidity and better medication tolerance. DAA therapy allowed for an increase in treatment rates of hepatitis C in patients on the liver transplant waiting list. With the popularization of DAA, there became a growing concern about the utility of hepatitis C-positive (HCV+) deceased liver donors, especially after treating HCV+ potential recipients on the transplant waiting list. METHODS: This is a retrospective, observational study using Mid-America Transplant Services (MTS) database from 2008 to 2017. Comparison was made before the widespread use of DAAs 2008-2013 (pre-DAA) against their common practice use 2014-2017 (post-DAA). All deceased liver donors with HCV antibody or nucleic acid positive results were evaluated. RESULTS: Between 2008 and 2017, 96 deceased liver donors were positive for HCV. In the pre-DAA era, 47 deceased liver donors were positive for HCV, of which 32 (68.1%) were transplanted and 15 (31.9%) were discarded. In the post-DAA era, a total of 49 HCV+ organs were identified, out of which 43 (87.8%) livers were transplanted and 6 (12.2%) were discarded. Discard rate was significantly higher in the pre-DAA population (31.9% vs. 12.2%, p = 0.026). Secondary analysis showed a distinct trend towards increased regional sharing and utilization of HCV+ donors. CONCLUSION: In order to reduce discard rates of HCV+ patients, our data suggest that transplant centers could potentially delay HCV treatment in patients on the transplant waitlist.

The Creation of a Novel Low-Cost Bench-Top Kidney Transplant Surgery Simulator and a Survey on Its Fidelity and Educational Utility.

Introduction Resident inexperience during time-sensitive vascular anastomoses of a kidney transplant can negatively impact outcomes. In light of this, we created a low-cost bench-top kidney transplant surgery simulator to help residents practice vascular anastomoses. Methods We searched for inexpensive materials to design an iliac fossa and kidney allograft. Eighteen residents with real-life kidney transplant experience trialed the simulator and scored its fidelity and educational utility on a 0-100 visual analog scale (VAS) survey. Results A 35.9 x 19.4 x 12.4 cm plastic box mimicked the iliac fossa. Hooks attached to the box's sidewall held under tension 1.27 and 0.64 cm diameter Penrose drains to replicate the external iliac vein and artery. A modified kidney-shaped stress ball with 1.27 x 4, 0.64 x 4, and 0.64 x 15 cm Penrose drains replicated a kidney allograft with its vein, artery, and ureter, respectively. Residents performed and assisted in vascular anastomoses on the simulator. The iliac fossa and allograft cost $20.20 and each practice run cost $7.20. Residents thought that the simulator was less difficult than real-life procedure, had acceptable fidelity levels, and they highly rated its educational utility. Conclusion Our novel low-cost bench-top kidney transplant surgery simulator focusing on vascular anastomoses received positive educational feedback from residents.

Asymptomatic Intestinal Malrotation Progressing to Midgut Volvulus in a Decompensated Alcoholic Cirrhotic Adult: A Rare Scenario Requiring Special Considerations.

Intestinal malrotation usually presents in the pediatric population with midgut volvulus requiring emergency Ladd's procedure. Rarely, it remains asymptomatic and is discovered incidentally only during adulthood when it seldom causes intestinal complications. The scenario of a cirrhotic adult being diagnosed with asymptomatic intestinal malrotation with subsequent intestinal complications is thus extremely rare and to our knowledge has not been previously reported. We describe a 56-year-old man with decompensated alcoholic cirrhosis (Child-Pugh class C, MELD score 22) who was initially observed after an incidental diagnosis of intestinal malrotation on computed tomography. Observation continued as his liver disease improved with alcohol cessation (Child-Pugh class A, MELD score 8). He later presented with a closed loop bowel obstruction secondary to midgut volvulus at the time of alcohol relapse and liver redecompensation (Child-Pugh class C, MELD score 22-29). He underwent emergency Ladd's procedure during which his midjejunum was volvulized into an internal hernia space created by a thick Ladd's band containing large varices. The postoperative course was complicated by ileus and loculated bacterial peritonitis. Based on our experience, we discuss special considerations with regard to the surgical technique and timing of Ladd's procedure when encountering intestinal malrotation in a cirrhotic adult with portal hypertension.

Reno-portal shunt for liver transplant, an alternative inflow for recipients with grade III-IV portal vein thrombosis: Tips for a better outcome.

INTRODUCTION: Portal vein thrombosis (PVT) poses an extremely difficult problem in cirrhotic patients who are in need of a liver transplant. The prevalence of PVT in patients with cirrhosis ranges from 0.6% to 26% Nery et al. (2015) [1]. The presence of PVT is associated with more technically difficult liver transplant and in certain cases can be a contraindication to liver transplant. The only option for these patients with extensive PVT would be a multi-visceral transplant, the later unfortunately has a much higher morbidity and mortality compared to liver only transplant Smith et al. (2016) [2]. An alternative approach is needed to provide a safe and reliable outcome. PRESENTATION OF CASE: In this case series, we present our experience with reno-portal shunt as an alternative inflow for the liver allograft. DISCUSSION: This approach appears to be safe with good long-term outcome.Although this technique has been described before, we provide additional considerations that produced good outcomes in our patients. CONCLUSION: We believe that meticulous preoperative planning with high-resolution triple phase CT imaging with a measurement of the diameter of the spleno-renal shunt along with a duplex scan measuring flow through the shunt is key to a successful transplantation. Moreover, appropriate donor liver size is also of extreme importance to avoid portal hypoperfusion.

Epstein-Barr Virus-Associated Acute Liver Failure Present in a 67-Year-Old Immunocompetent Female.

Acute liver failure (ALF) is a rare illness with a high mortality rate. The only favorable management is emergent liver transplantation. About 13% of ALF cases have no clear etiology. Epstein-Barr virus (EBV)-associated ALF accounts for less than 1% of all ALF cases, and is seen mostly in adults younger than 40 years. There are only a few cases of EBV-associated ALF in elderly immunocompromised adults. We report a case of ALF in an immunocompetent 67-year-old woman caused by EBV infection that was treated by orthotopic liver transplantation (OLT). The diagnosis of EBV-associated ALF was established by EBV-DNA polymerase chain reaction (PCR) and EBV-encoded RNA (EBER-RNA) in situ hybridization (EBER-RISH). The patient is currently doing well 6 months after transplantation without any evidence of clinical EBV infection. This case illustrates the importance of early recognition and diagnosis of EBV-associated ALF by detection of EBV from liver biopsy, especially when patients are immunocompetent and other causes are excluded. To the best of our knowledge, this is the first case of EBV-associated ALF present in an immunocompetent elderly female.

Hepatectomy cures a cough: giant cavernous hemangioma in a patient with persistent cough.

Cavernous hemangiomas are the most common type of benign liver tumor. Although these tumors are often asymptomatic, they can occur with an array of symptoms. The authors describe a case of a 51-year-old man who presented to the emergency department with a relentless cough, nausea, and abdominal pain. Results of a computed tomography scan suggested the patient had a giant cavernous hemangioma on his liver; microscopic evaluation confirmed this diagnosis. The hemangioma was initially deemed unresectable and the patient was treated with one session of hepatic artery embolization. The embolization was unsuccessful at easing the patient's symptoms, however, and a hepatic lobectomy and resection was performed. After surgical intervention, the patient's symptoms resolved. The present case illustrates an unusual instance in which chronic cough was cured through hepatectomy for giant cavernous hemangioma. To our knowledge, no reports of coughing as a primary symptom of giant cavernous hemangioma have been previously reported in the literature.

Biliary-venous fistula complicating transjugular intrahepatic portosystemic shunt presenting with recurrent bacteremia, jaundice, anemia and fever.

A 50-year-old White man with noncirrhotic portal hypertension presented with bleeding from gastric varices. Bleeding was initially managed with band ligation and subsequent transjugular intrahepatic portosystemic shunt (TIPS). Over the next few months, the patient had recurrent episodes of anemia, jaundice, fever and polymicrobial bacteremia. Computed tomography (CT) of the abdomen and chest, upper and lower endoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and echocardiography failed to explain the bacteremia and anemia. Follow-up CT scan and Doppler sonography 9 months after placement showed TIPS was occluded. Repeat ERCP showed a bile leak with free run-off of contrast from the left hepatic duct into a vascular structure. The patient's status was upgraded for liver transplantation with Regional Review Board agreement and subsequently received a liver transplant. Gross examination of the native liver demonstrated a fistula between the left bile duct and the middle hepatic vein. Pathologic evaluation confirmed focal necrosis of the left hepatic duct communicating with an occluded TIPS and nodular regenerative hyperplasia consistent with noncirrhotic portal hypertension. Infection is rarely reported in a totally occluded TIPS. Biliary fistulas in patent TIPS have been treated by endoluminal stent graft and endoscopic sphincterotomy with biliary stent placement. Liver transplantation may be the preferred treatment if TIPS becomes infected following its complete occlusion.