Pre-Hepatectomy Assessment of Bile Transporter Expression by Gadoxetic Acid-Enhanced MRI in a Rat Model of Liver Cirrhosis.

BACKGROUND: Gadoxetic acid is a liver-specific intravenous T1 magnetic resonance (MR) contrast agent that is excreted via the hepatobiliary system. We hypothesize that hepatocyte expressions of bile transporters (OATP1 and MRP2) correlate with dynamic profile of Gadoxetic acid enhanced (GE)-MR imaging (MRI). METHODS: Two groups of rats, control (n = 6) and cirrhosis (n = 12), received gadoxetic acid enhanced MRI followed by 70% hepatectomy. The change in MR signal intensity from the baseline before the contrast injection (ΔSI) was analyzed every minute for 30 min. Dynamic signal intensity retention ratio (DSR) was defined as the mean ΔSI of the third 10-minmin period divided by the first 10-minmin period. Real-time PCR was utilized to quantify mRNA expressions. RESULTS: Compared to the control, cirrhosis group demonstrated lower mRNA levels of OATP1 (0.038 ± 0.020 vs. 0.232 ± 0.0979; p = 0.004), MRP2 (0.201 ± 0.084 vs. 0.7567 ± 0.254; p = 0.002), and OATP1/MRP2 mRNA ratio (0.193 ± 0.065 vs. 0.342 ± 0.206; p = 0.032). DSR was higher in the cirrhosis group (0.678 ± 0.554 vs -0.125 ± 0.839; p = 0.033). In the cirrhosis group, there was an inverse correlation between the ratios of OATP1/MRP2 mRNA and DSR (R = -0.709, p = 0.01). CONCLUSION: Bile transporters OATP1/MRP2 mRNA expression ratio in rat liver tissue decreased with DMN-induced liver injury. The expressions of bile transporters correlated with GE-MRI DSR. The GE-MRI DSR has potential utility in qualifying OATP1/MRP2 mRNA expression.

Human Parechovirus as a Cause of Isolated Pediatric Acute Liver Failure.

Among infants, almost half of acute liver failure cases are classified as indeterminate, whereas only a small number of cases show a documented viral infection. We present the first reported case of isolated acute hepatic failure in an infant in the setting of a human parechovirus (HPeV) infection. HPeV also may have been contributory to the posttransplant complication of 2 intussusceptions. This is a 10-month-old girl who presented with only symptoms of fussiness and was noted to have progressive decline in synthetic liver function as well as worsening coagulopathy requiring a liver transplant. The acute liver failure was in the setting of a positive serum RNA HPeV, subtype 3 (HPeV-3), after extensive diagnostic testing with genetic, autoimmune, and infectious causes otherwise negative. After liver transplantation, the postoperative course was complicated by both an ileal-ileal intussusception as well as a jejunal intussusception. Viral testing in pediatric acute liver failure is often performed, but the workup is frequently incomplete. This case report would support more extensive viral testing in this population of patients. In the setting of HPeV, clinicians could be alerted to the possibility of delayed gastrointestinal pathology in the posttransplant phase. Wider use of routine HPeV testing may more clearly define the variable clinical presentations and outcomes.

Hydroxocobalamin for Vasoplegic Syndrome in Liver Transplantation: Restoration of Blood Pressure Without Vasospasm.

Systemic vasoplegia is common in patients undergoing liver transplantation. In this report, we present a case in which treatment with conventional vasopressors caused peripheral arterial spasm, rendering arterial blood pressure monitoring impossible. Administration of methylene blue resolved the vasospasm; however, concern for toxic dose requirements limited its use. Hydroxocobalamin administration resolved the vasospasm and increased blood pressure without the potential adverse effects seen with methylene blue. This case represents the first report of hydroxocobalamin use in liver transplantation and may represent a new option for the treatment of vasoplegia and the potential vasospasm that may result from traditional vasopressors.

Portal Steal Syndrome After Full-Size Deceased Donor Liver Transplantation.

Successful liver transplantation typically results in an immediate decrease in intrahepatic resistance accompanied by an initial increased hepatopedal portal flow. Within a short period of time, the portal hypertension resolves and the variceal shunts involute. However, in situations in which intrahepatic vascular resistance to venous flow remains elevated, significant hepatofugal portal flow may continue through persistent mesenteric shunts. This situation, portal steal, can result in decreased perfusion of the liver graft leading to graft dysfunction, failure, and potentially recipient death. This report details a case and the surrounding literature to highlight appropriate diagnosis and management in these patients.

Changing paradigms in organ preservation and resuscitation.

PURPOSE OF REVIEW: Shortage of donor organs has increased consideration for use of historically excluded grafts. Ex-vivo machine perfusion is an emerging technology that holds the potential for organ resuscitation and reconditioning, potentially increasing the quality and number of organs available for transplantation. This article aims to review the recent advances in machine perfusion and organ preservation solutions. RECENT FINDINGS: Flow and pressure-based machine perfusion has shown improved kidney graft function and survival, especially among expanded criteria donors. Pressure-based machine perfusion is demonstrating promising results in preservation and resuscitation of liver, pancreas, heart, and also lung grafts. August 2014 marked Food and Drug Administration approval of XPS XVIVO Perfusion System (XVIVO Perfusion Inc., Englewood, Colorado, USA), a device for preserving and resuscitating lung allografts initially considered unsuitable for transplantation. Although there is no consensus among physicians about the optimal preservation solution, adding antiapoptotic and cell protective agents to preservation solutions is an interesting research area that offers potential to improve preservation. SUMMARY: Ex-vivo machine perfusion of solid organs is a promising method that provides the opportunity for resuscitation and reconditioning of suboptimal grafts, expanding the number and quality of donor organs.

Global discovery of colonization determinants in the squid symbiont Vibrio fischeri.

Animal epithelial tissue becomes reproducibly colonized by specific environmental bacteria. The bacteria (microbiota) perform critical functions for the host's tissue development, immune system development, and nutrition; yet the processes by which bacterial diversity in the environment is selected to assemble the correct communities in the host are unclear. To understand the molecular determinants of microbiota selection, we examined colonization of a simplified model in which the light organ of Euprymna scolopes squid is colonized exclusively by Vibrio fischeri bacteria. We applied high-throughput insertion sequencing to identify which bacterial genes are required during host colonization. A library of over 41,000 unique transposon insertions was analyzed before and after colonization of 1,500 squid hatchlings. Mutants that were reproducibly depleted following squid colonization represented 380 genes, including 37 that encode known colonization factors. Validation of select mutants in defined competitions against the wild-type strain identified nine mutants that exhibited a reproducible colonization defect. Some of the colonization factors identified included genes predicted to influence copper regulation and secretion. Other mutants exhibited defects in biofilm development, which is required for aggregation in host mucus and initiation of colonization. Biofilm formation in culture and in vivo was abolished in a strain lacking the cytoplasmic chaperone DnaJ, suggesting an important role for protein quality control during the elaboration of bacterial biofilm in the context of an intact host immune system. Overall these data suggest that cellular stress responses and biofilm regulation are critical processes underlying the reproducible colonization of animal hosts by specific microbial symbionts.

Renal mucormycosis: a rare and potentially lethal complication of kidney transplantation.

Renal mucormycosis is a rare and potentially lethal complication of kidney transplantation. We describe two cases of renal mucormycosis following deceased donor kidney transplantation. This is the second report of renal mucormycosis following kidney transplantation in the United States, and the first case of renal mucormycosis infection presumed to be of recipient origin. Case A had an early presentation of mucormycosis isolated to the kidney allograft. He had an unexpected rise in serum creatinine and leukocytosis necessitating allograft biopsy which showed mucormycosis. He underwent transplant nephrectomy on posttransplant day 11, was treated with amphotericin B, and discharged home on posttransplant day 22. Case B had a late presentation of renal mucormycosis, preceded by a cutaneous manifestation. One year after kidney transplantation he had a nonhealing knee ulcer which on biopsy showed cutaneous mucormycosis. Treatment included aggressive debridement and amphotericin B. Allograft biopsy showed mucormycosis, necessitating transplant nephrectomy. He was discharged to a rehabilitation facility and died from noninfectious causes. Review of the published literature of renal mucormycosis cases following kidney transplantation reveals a mortality rate of more than 50%. The key to successful outcome is early recognition, prompt institution of surgical debridement of all infected tissue, and appropriate antifungal therapy.

Donor and recipient BKV-specific IgG antibody and posttransplantation BKV infection: a prospective single-center study.

BACKGROUND: The study evaluated the relationship of pretransplantation BK virus (BKV)-specific donor and recipient serostatus to posttransplantation BKV infection. METHODS: Two hundred forty adult de novo kidney-only recipients and 15 pediatric recipients were prospectively enrolled and followed for a minimum of 18 months. Pretransplantation BKV serostatus was available for 192 adult and 11 pediatric donor-recipient pairs. Based on BKV-specific IgG enzyme immunoassay ≥8 units, subjects were divided into four groups: D+R+, D+R-, D-R+, and D-R-. BKV DNA surveillance was performed at 1, 3, 6, 12, and 24 months. The outcomes studied were development of any BKV infection, viremia, and significant viremia (≥10,000 copies/mL plasma). RESULTS: Of the 192 adult subjects (D+R- [n=41], D+R+ [n=42], D-R+ [n=41], and D-R- [n=68]), 89 of 192 developed any BKV infection and 62 of 89 developed BK insignificant viremia (n=33) and significant viremia (n=29). Any BKV infection developed in 25 of 41, 22 of 42, 17 of 41, and 25 of 68 in the D+R-, D+R+, D-R+, and D-R- groups, respectively. Any viremia (20 of 41) and significant viremia (10 of 41) seen in the D+R- group was significantly higher than other groups (P=0.014). In 11 pediatric recipients, infection was seen only in the D+R- group. Overall, infection was highest in the D+R- group and lowest in the D-R- group. CONCLUSIONS: BKV serostatus can be used to risk stratify patients for posttransplantation infection.

Anomalous hepatic vein anatomy of left lateral section grafts and customized unification venoplasty for pediatric living donor liver transplantation.

In liver transplantation, a left lateral section (LLS) graft may have an unusual variant left hepatic vein (LHV) anatomy. This study was designed to analyze the incidence of unusual LHV variants and to determine technical methods for effective reconstruction in infant recipients weighing approximately 10 kg or less. The study comprised 3 parts: an LHV variation analysis, a simulation-based design for the technical modification of graft LHV venoplasty, and its clinical application. The LHV anatomy of 300 potential LLS graft donors was classified into 4 types according to the number and location of the hepatic vein openings: (1) a single opening (n = 218 or 72.7%); (2) 2 large adjacent openings (n = 29 or 9.7%); (3) 2 adjacent openings, 1 large and 1 small (n = 34 or 11.3%); and (4) 2 widely spaced openings (n = 19 or 6.3%). Types 2 and 3 required wedged unification venoplasty, and type 4 required additional vein interposition. In a series of 49 cases using LLS grafts, the graft hepatic vein complication rate was 4.5% at 3 years; stenting was necessary for 1 of the 36 type 1 LHV grafts (2.8%) and for 1 of the 13 type 2-4 LHV grafts (7.7%, P = 0.46). A customized interposition-wedged unification venoplasty technique for coping with type 4 vein variations was developed with a simulation-based approach, and it was successfully applied to a 10-month-old male infant receiving an LLS graft with a type 4 LHV. In conclusion, nearly all LHV variations can be effectively managed with customized unification venoplasty. These venoplasty techniques represent beneficial surgical options as part of graft standardization for hepatic vein reconstruction in pediatric living donor liver transplantation.

Anaphylaxis on reperfusion during liver transplantation with coagulopathy.

We present a case in which anaphylaxis on hepatic reperfusion during liver transplantation presented only with hypotension and coagulopathy. There were no cutaneous manifestations or clinical features distinguishing anaphylaxis from postreperfusion syndrome. The recipient regularly consumed seafood, and the organ donor died of anaphylaxis to shellfish. The trigger for anaphylaxis was postulated to be passive transfer of immunoglobulin to the recipient. Anesthesiologists should be notified of donor factors to anticipate anaphylaxis. In this report, we discuss coagulopathy of anaphylaxis and contrast it with disseminated intravascular coagulation.

Diagnostic accuracy of solid phase HLA antibody assays for prediction of crossmatch strength.

Solid phase antibody assays are increasingly used to provide quantitative measures of donor-specific HLA antibodies for assessment of pretransplant risk, although cell-based crossmatches continue to serve as gold standards for determination of donor HLA antibody strength. This study determined the ability of HLA antibody solid phase assays to predict the strength of cell-based flow cytometric (FC) and complement-dependent cytotoxicity (CDC) crossmatches. Eighty-two recipient/donors pairs were analyzed using receiver operating characteristic (ROC) curve analyses to determine the accuracy of donor-specific median fluorescence intensity values (Σ MFI) from single antigen bead assays for predicting strong FC and CDC crossmatches. Diagnostic sensitivity and specificity of optimal Σ MFI values were highest for predicting strong T cell FCs. Σ MFI values showed good sensitivity for predicting positive direct and AHG-augmented CDC crossmatches (91% and 94%, respectively), but with lower specificity (67% each). Specificity and sensitivity for predicting positive B cell CDC crossmatches were 73% and 84%. Σ MFI values derived from single antigen bead assays can predict strong flow and positive CDC crossmatches, but with tradeoffs between sensitivity and specificity. The results support the use of solid phase assays for quantitative virtual crossmatching and as a replacement for cell-based crossmatching.

Draft genome sequence of Vibrio fischeri SR5, a strain isolated from the light organ of the Mediterranean squid Sepiola robusta.

Here, we describe the draft genome sequence of Vibrio fischeri SR5, a squid symbiotic isolate from Sepiola robusta in the Mediterranean Sea. This 4.3-Mbp genome sequence represents the first V. fischeri genome from an S. robusta symbiont and the first from outside the Pacific Ocean.

Patient access to transplantation with an Internet-identified live kidney donor: a survey of U.S. centers.

BACKGROUND: To investigate legitimate transplantation in the United States with an Internet-identified live donor organ, from the patient's perspective, kidney centers were contacted by a researcher posing as an ideal patient and recipient pair seeking to find a center to perform their transplant. METHODS: Responses were obtained with fewer than three phone calls and within less than 2 wk from 100 of 206 UNOS listed centers; 42 pediatric or inactive centers were excluded. RESULTS: A total of 37% (76 of 100) indicated a willingness to consider such a transplant. Eight centers acknowledged having previously performed one, with 100% (8/8) of these indicating that they would still consider future participation. CONCLUSION: Large numbers of Internet-facilitated transplants are not yet being performed in the United States. Because it was possible to elicit a definite answer with 3 or fewer calls at only 49% of centers, we conclude that a significant proportion of centers are not providing easy access to potential donors and recipients. Agreeable centers were clustered geographically, suggesting that multiple factors may be influencing opinions. 100% of agreeable centers required their own standard evaluation of the donor and recipient and indicated that financial exchange between the pair was illegal. We conclude that Internet-based live donor kidney transplants are occurring and have received cautious acceptance at a significant number of legitimate centers. The utility of asking "How did the recipient-donor pair present to our institution" may no longer be relevant. We suggest that every pair seeking access to legitimate transplantation should undergo standardized evaluation with open acknowledgment of the relationship as a modifier.