Preoperative thrombelastography maximum amplitude predicts massive transfusion in liver transplantation.

BACKGROUND: Massive transfusion (MT) is frequently required during liver transplantation. Risk stratification of transplant patients at risk for MT is an appealing concept but remains poorly developed. Thrombelastography (TEG) has recently been shown to reduce mortality when used for trauma resuscitation. We hypothesize that preoperative TEG can be used to risk stratify patients for MT. MATERIAL AND METHODS: Liver transplant patients had blood drawn before surgical incision and assayed via TEG. Preoperative TEG measurements were collected in addition to standard laboratory coagulation tests. TEG variables including R-time (reaction time), angle, maximum amplitude (MA), and LY30 (clot lysis 30 min after MA) were correlated to red blood cell units, plasma (fresh frozen plasma), cryoprecipitate, and platelets during the first 24 h after surgery and tested for their performance using a receiver-operating characteristic curve. RESULTS: Twenty-eight patients were included in the analysis with a median Model for End-Stage Liver Disease score of 17; 36% received a MT. The TEG variables associated with MT (defined as ≥10 red blood cell units/24 h) were a low MA (P < 0.001) and low angle (P = 0.014). A high international normalized ratio of prothrombin time (P = 0.003) and low platelet count (P = 0.007) were also associated with MT. MA had the highest area under the curve (0.861) followed by international normalized ratio of prothrombin time (0.803). An MA of less than 47 mm has a sensitivity of 90% and specificity of 72% to predict a MT. MA was the only coagulation variable that correlated strongly to all blood products transfused. CONCLUSIONS: TEG MA has a high predictability of MT during liver transplantation. The use of TEG preoperatively may help guide more cost effective blood bank preparation for this procedure as only a third of patients required a MT.

Signaling through hepatocellular A2B adenosine receptors dampens ischemia and reperfusion injury of the liver.

Ischemia and reperfusion significantly contributes to the morbidity and mortality of liver surgery and transplantation. Based on studies showing a critical role for adenosine signaling in mediating tissue adaptation during hypoxia, we hypothesized that signaling events through adenosine receptors (ADORA1, ADORA2A, ADORA2B, or ADORA3) attenuates hepatic ischemia and reperfusion injury. Initial screening studies of human liver biopsies obtained during hepatic transplantation demonstrated a selective and robust induction of ADORA2B transcript and protein following ischemia and reperfusion. Subsequent exposure of gene-targeted mice for each individual adenosine receptor to liver ischemia and reperfusion revealed a selective role for the Adora2b in liver protection. Moreover, treatment of wild-type mice with an Adora2b-selective antagonist resulted in enhanced liver injury, whereas Adora2b-agonist treatment was associated with attenuated hepatic injury in wild-type, but not in Adora2b(-/-) mice. Subsequent studies in mice with Adora2b deletion in different tissues--including vascular endothelia, myeloid cells, and hepatocytes--revealed a surprising role for hepatocellular-specific Adora2b signaling in attenuating nuclear factor NF-κB activation and thereby mediating liver protection from ischemia and reperfusion injury. These studies provide a unique role for hepatocellular-specific Adora2b signaling in liver protection during ischemia and reperfusion injury.

Defining long-term outcomes with living donor liver transplantation in North America.

OBJECTIVES: To compare long-term survival of living donor liver transplant (LDLT) at experienced transplant centers with outcomes of deceased donor liver transplant and identify key variables impacting patient and graft survival. BACKGROUND: The Adult-to-Adult Living Donor Liver Transplantation Cohort Study is a prospective multicenter National Institutes of Health study comparing outcomes of LDLT and deceased donor liver transplant and associated risks. METHODS: Mortality and graft failure for 1427 liver recipients (963 LDLT) enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study who received transplant between January 1, 1998, and January 31, 2014, at 12 North American centers with median follow-up 6.7 years were analyzed using Kaplan-Meier and multivariable Cox models. RESULTS: Survival probability at 10 years was 70% for LDLT and 64% for deceased donor liver transplant. Unadjusted survival was higher with LDLT (hazard ratio = 0.76, P = 0.02) but attenuated after adjustment (hazard ratio = 0.98, P = 0.90) as LDLT recipients had lower mean model for end-stage liver disease (15.5 vs 20.4) and fewer received transplant from intensive care unit, were inpatient, on dialysis, were ventilated, or with ascites. Posttransplant intensive care unit days were less for LDLT recipients. For all recipients, female sex and primary sclerosing cholangitis were associated with improved survival, whereas dialysis and older recipient/donor age were associated with worse survival. Higher model for end-stage liver disease score was associated with increased graft failure. Era of transplantation and type of donated lobe did not impact survival in LDLT. CONCLUSIONS: LDLT provides significant long-term transplant benefit, resulting in transplantation at a lower model for end-stage liver disease score, decreased death on waitlist, and excellent posttransplant outcomes. Recipient diagnosis, disease severity, renal failure, and ages of recipient and donor should be considered in decision making regarding timing of transplant and donor options.Clinical Trials ID: NCT00096733.

Equilibrative nucleoside transporter (ENT)-1-dependent elevation of extracellular adenosine protects the liver during ischemia and reperfusion.

UNLABELLED: Ischemia and reperfusion-elicited tissue injury contributes to morbidity and mortality of hepatic surgery and during liver transplantation. Previous studies implicated extracellular adenosine signaling in liver protection. Based on the notion that extracellular adenosine signaling is terminated by uptake from the extracellular towards the intracellular compartment by way of equilibrative nucleoside transporters (ENTs), we hypothesized a functional role of ENTs in liver protection from ischemia. During orthotopic liver transplantation in humans, we observed higher expressional levels of ENT1 than ENT2, in conjunction with repression of ENT1 and ENT2 transcript and protein levels following warm ischemia and reperfusion. Treatment with the pharmacologic ENT inhibitor dipyridamole revealed elevations of hepatic adenosine levels and robust liver protection in a murine model of liver ischemia and reperfusion. Studies in gene-targeted mice for Ent1 or Ent2 demonstrated selective protection from liver injury in Ent1(-/-) mice. Treatment with selective adenosine receptor antagonists indicated a contribution of Adora2b receptor signaling in ENT-dependent liver protection. CONCLUSION: These findings implicate ENT1 in liver protection from ischemia and reperfusion injury and suggest ENT inhibitors may be of benefit in the prevention or treatment of ischemic liver injury.

Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation.

BACKGROUND & AIMS: IL28B single nucleotide polymorphisms are strongly associated with spontaneous HCV clearance and treatment response in non-transplant populations. A DDX58 single nucleotide polymorphism is associated with the antiviral response of innate lymphocytes. We aimed at evaluating the associations of donor and recipient IL28B (rs12979860 and rs8099917) and DDX58 (rs10813831) genotypes with severity of HCV recurrence after liver transplantation. METHODS: In a case-control study of 523 liver transplantation recipients with HCV, we matched severe with mild recurrent HCV based on 2-year clinical and histologic follow-up. A total of 440 liver transplantation recipients (severe, n=235; mild, n=205) with recipient DNA and 225 (severe, n=123; mild, n=102) with both recipient and donor DNA were analyzed. RESULTS: IL28B [rs12979860, non-CC (vs. CC) and rs8099917, non-TT (vs. TT)] in the recipient-only analysis had higher risk of severe recurrent HCV [OR 1.57 and 1.58, p<0.05]. However, for the 225 with donor and recipient DNA, IL28B rs12979860 CC (vs. non-CC) and rs8099917 TT (vs. non-TT) and DDX58 rs10813831 non-GG (vs. GG) were associated with more (not less) severe recurrent HCV. The greatest risk of severe recurrent HCV was for rs12979860 CC donors in non-CC recipients (OR 7.02, p <0.001, vs. non-CC donor/recipient) and for rs8099917 TT donors in non-TT recipients (OR 5.78, p=0.001, vs. non-TT donor/recipient). These associations persisted after controlling for donor age, donor race, and donor risk index. CONCLUSIONS: IL28B and DDX58 single nucleotide polymorphisms that are favorable when present in the non-transplant setting or in the recipient are unfavorable when present in a donor liver graft.

Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the United States With hepatitis B immunoglobulin and nucleoside/nucleotide analogues.

Reinfection with hepatitis B virus (HBV) after liver transplantation (LT) may favor the recurrence of hepatocellular carcinoma (HCC), and combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogues may reduce HBV recurrence after LT. To test associations between HBV, HCC, and survival, we performed a retrospective chart review of patients undergoing LT for HBV between January 1985 and December 2010 at 7 US transplant centers. After we divided the patients into 3 eras based on evolving strategies in antiviral therapy (1985-1994, 1995-2004, and 2005-2010), we reviewed 16 variables to determine whether there were associations between survival and HCC recurrence. Seven hundred thirty-eight patients underwent transplantation for HBV, and 354 (48.0%) had concomitant HCC, which recurred in 58 patients (16.4%). Three-year survival was much better in era 3 versus era 1 (87% versus 40%, P = 0.001), and the incidence of HCC recurrence was lower (12% versus 29%, P = 0.009). The lungs were the most frequent first site of HCC recurrence, and they were followed by the liver. A multivariate analysis showed that HBV reinfection, HCC recurrence, and HBIG use were associated with worse survival (P < 0.001, P < 0.001, and P = 0.002, respectively); HCC recurrence and stage 3 HCC, among other factors, were associated with HBV reinfection (P < 0.001 and P = 0.004); and stage 3 HCC, vascular invasion of the explanted tumor, and post-LT chemotherapy were associated with HCC recurrence (P = 0.008, P < 0.001, and P < 0.001, respectively). Patients with HBV reinfection were 3.6 times more likely than patients without HBV to have HCC recurrence. These data suggest further study of attempts at LT for patients with HBV and HCC beyond the Milan criteria if their HBV is aggressively and successfully treated.

Multicenter review of liver transplant for hepatitis B-related liver disease: disparities in gender and ethnicity.

Orthotopic liver transplantation (OLT) is the preferred treatment for selected patients with hepatitis B virus (HBV)-related liver disease. This study aimed to (i) define long-term outcomes following OLT for HBV; (ii) to quantify the incidence of HBV recurrence (rHBV) as it relates to anti-HBV treatment; and (iii) to determine outcomes for specific patient subgroups. We performed a retrospective chart review of 738 patients undergoing OLT between 1985 and 2010 at seven US transplant centers and divided the patients into 3 eras, 1985-1994, 1995-2004, and 2005-2010, based on hepatitis B immunoglobulin and antiviral therapies. In Era 3, female gender (p = 0.002), recurrent hepatocellular cancer (p < 0.001), and retransplantation (p = 0.01) were significantly associated with worse survival on multivariate analysis. Survival at three yr was poor for all ethnicities in Era 1, but significantly improved for all except black Americans by Era 3. Era 2 data showed a continued increase in rHBV from five to 10 yr (16.6%, 26.2%). In conclusion, while OLT outcomes have improved because of combination antiviral and immunoglobulin therapy, women and black Americans may not have realized an equal benefit. The rate of rHBV is significant even 10 yr post-transplant with survival affected.

Incentives for organ donation: proposed standards for an internationally acceptable system.

Incentives for organ donation, currently prohibited in most countries, may increase donation and save lives. Discussion of incentives has focused on two areas: (1) whether or not there are ethical principles that justify the current prohibition and (2) whether incentives would do more good than harm. We herein address the second concern and propose for discussion standards and guidelines for an acceptable system of incentives for donation. We believe that if systems based on these guidelines were developed, harms would be no greater than those to today's conventional donors. Ultimately, until there are trials of incentives, the question of benefits and harms cannot be satisfactorily answered.

Choledochoduodenostomy continues to be a safe alternative for biliary reconstruction in deceased-donor liver transplantation.

Debate continues as to whether choledochoduodenostomy (CDD) can be used instead of Roux-en-Y choledochojejunostomy (CDJ) when duct-to-duct (DTD) is not an option. We hypothesized that CDD and CDJ had similar rates of complications. All deceased-donor liver transplantations from September 2011 to March 2020 were categorized by biliary reconstruction. Primary outcomes were bleeding, bile leak, anastomotic stricture, and cholangitis. Of the 1,086 patients, 812 (74.8%) received a DTD; 225 (20.7%) received a CDD; and 49 (4.5%) received a CDJ. Cholangitis was significantly higher in CDJ compared to DTD and CDD (26.5% vs 6% vs 13.8%, p < 0.0001). When controlling for significant confounders, CDJ had 10.2 higher odds of cholangitis (95% CI 4.4-23.2) compared to DTD, and 3.3 higher odds compared to CDD (95% CI 1.4-7.8). When compared to DTD, CDJ and CDD had significantly lower odds of stricture. CDD continues to be a safe alternative for biliary reconstruction in deceased-donor liver transplantation.

Outcomes of adult living donor liver transplantation: comparison of the Adult-to-adult Living Donor Liver Transplantation Cohort Study and the national experience.

The study objectives were to determine whether the findings of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) reflect the U.S. national experience and to define risk factors for patient mortality and graft loss in living donor liver transplantation (LDLT). A2ALL previously identified risk factors for mortality after LDLT, which included early center experience, older recipient age, and longer cold ischemia time. LDLT procedures at 9 A2ALL centers (n = 702) and 67 non-A2ALL centers (n = 1664) from January 1998 through December 2007 in the Scientific Registry of Transplant Recipients database were analyzed. Potential predictors of time from transplantation to death or graft failure were tested using Cox regression. No significant difference in overall mortality between A2ALL and non-A2ALL centers was found. Higher hazard ratios (HRs) were associated with donor age (HR = 1.13 per 10 years, P = 0.0002), recipient age (HR = 1.20 per 10 years, P = 0.0003), serum creatinine levels (HR = 1.52 per loge unit increase, P < 0.0001), hepatocellular carcinoma (HR = 2.12, P<0.0001) or hepatitis C virus (HR = 1.18, P = 0.026), intensive care unit stay (HR = 2.52, P< 0.0001) or hospitalization (HR = 1.62, P < 0.0001) versus home, earlier center experience (LDLT case number 15: HR = 1.61, P < 0.0001, and a cold ischemia time >4.5 hours (HR = 1.79, P = 0.0006). Except for center experience, risk factor effects between A2ALL and non-A2ALL centers were not significantly different. Variables associated with graft loss were identified and showed similar trends. In conclusion, mortality and graft loss risk factors were similar in A2ALL and non-A2ALL centers. These analyses demonstrate that findings from the A2ALL consortium are relevant to other centers in the U.S. performing LDLT, and conclusions and recommendations from A2ALL may help to guide clinical decision making.

Differential effects of plasma and red blood cell transfusions on acute lung injury and infection risk following liver transplantation.

Patients with chronic liver disease have an increased risk of developing transfusion-related acute lung injury (TRALI) from plasma-containing blood products. Similarly, red blood cell transfusions have been associated with postoperative and nosocomial infections in surgical and critical care populations. Patients undergoing liver transplantation receive large amounts of cellular and plasma-containing blood components, but it is presently unclear which blood components are associated with these postoperative complications. A retrospective cohort study of 525 consecutive liver transplant patients revealed a perioperative TRALI rate of 1.3% (7/525, 95% confidence interval = 0.6%-2.7%), which was associated with increases in the hospital mortality rate [28.6% (2/7) versus 2.9% (15/518), P = 0.02] and the intensive care unit length of stay [2 (1-11 days) versus 0 days (0-2 days), P = 0.03]. Only high-plasma-containing blood products (plasma and platelets) were associated with the development of TRALI. Seventy-four of 525 patients (14.1%) developed a postoperative infection, and this was also associated with increased in-hospital mortality [10.8% (8/74) versus 2.0% (9/451), P < 0.01] and a prolonged length of stay. Multivariate logistic regression determined that the number of transfused red blood cell units (adjusted odds ratio = 1.08, 95% confidence interval = 1.02-1.14, P < 0.01), the presence of perioperative renal dysfunction, and reoperation were significantly associated with postoperative infection. In conclusion, patients undergoing liver transplantation have a high risk of developing postoperative complications from blood transfusion. Plasma-containing blood products were associated with the development of TRALI, whereas red blood cells were associated with the development of postoperative infections in a dose-dependent manner.

Choledochoduodenostomy in pediatric liver transplantation.

UNLABELLED: Reconstruction of the bile ducts during pediatric liver transplantation is generally performed by a Roux-en-Y CDJ because direct duct-to-duct anastomosis CC is often not possible. Anastomosis of the donor liver bile duct to the duodenum CDD provides another option. We provide preliminary evidence that CDD is an alternative technique for biliary reconstruction when CC is not possible in pediatric liver transplant recipients that have a hostile abdomen or to preserve bowel length. METHODS: From 2007 to 2008, a total of 19 pediatric cadaveric liver transplants were performed at our center. Four of the 19 had a bile duct reconstruction by CDD. RESULTS: CDD reconstruction was used in patients who received a liver transplant for a diagnosis of PSC, congenital hepatic fibrosis, biliary atresia, and Alagille syndrome. The ages of the patients were 17 and 10 yr and 10 and 17 months. Three grafts were whole cadaveric livers, and one was a reduced left lobe. CDD was used to revise a prior anastomosis in one patient who had a previous Roux-en-Y that was unusable during the retransplant, and another to repair a stricture in a second patient with a CC. We also performed a CDD in a patient with a hostile abdomen from previous surgery, and another patient to avoid short gut syndrome that a Roux-en-Y may have created. All patients are alive with functioning grafts with a follow-up of at least one yr. None of the patients developed clinically significant biliary complications (leak, stricture, cholangitis). CONCLUSION: Our preliminary experience suggests that CDD is an option for biliary reconstruction in pediatric transplant patients with hostile abdomens or to preserve bowel length.

The influence of OKT3 therapy on hepatocellular carcinoma recurrence following liver transplantation.

INTRODUCTION: Cancer recurrence following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) is a significant obstacle in up to 10-20% of recipients. Recent evidence suggests that anti-CD3 antibody (OKT3) therapy may be associated with increased rates of HCC recurrence. METHODS: At the University of Colorado Transplant Center, 173 patients underwent OLT for end-stage liver disease with concomitant HCC between 1997 and 2008. Nine clinical and pathologic variables were analyzed to test the association between OKT3 therapy for steroid-resistant rejection (SRR) and HCC recurrence-free survival. RESULTS: Overall, the rate of HCC recurrence in this cohort was low and comparable across treatment groups (8.7%). Multivariate analysis reveals that increasing tumor diameter and differentiation have a negative impact on HCC recurrence-free survival. CONCLUSIONS: While several pathologic variables appear to influence outcome, we found no association between OKT3 therapy for SRR and HCC recurrence or survival.

Adult right lobe live donor liver transplantation without reconstruction of the middle hepatic vein: a single-center study of 109 cases.

We report our experience in adult-to-adult right hepatic lobe living donor liver transplantation (ALDLT) using extension of the hepatectomy transection line medially to incorporate the right middle hepatic vein branches into the donor graft. One hundred and nine ALDLT were performed at the University of Colorado from August 1997 to December 2005. Donors were screened preoperatively for hepatic venous anatomy compatible with this technique. Of the 109 ALDLT, the first 10 did not include the right middle hepatic vein branches in the graft. As such, three patients required retransplantation, two from graft loss because of venous congestion. Of the next 99 transplants, only 11 required retransplantation and none because of venous congestion. This approach allows adequate venous outflow through the right hepatic vein more than 1 cm, which is demonstrated by the absence of graft loss from venous congestion and superior graft survival.

Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma.

Experience with sirolimus (SRL)-based immunosuppression following orthotopic liver transplantation (OLT) is rapidly accumulating. In combination with calcineurin inhibitors (CNIs), SRL may reduce the incidence of acute rejection and lower overall required drug levels. This study sought to quantify long-term outcome following OLT in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC) who were treated with an SRL-based regimen as a primary therapy. From January 2000 to June 2007, 97 patients underwent OLT for end-stage liver disease and HCC at the University of Colorado Health Sciences Center. Of those, 45 patients received SRL, in addition to CNIs, as a component of their primary immunosuppression regimen post-OLT. Conversely, 52 patients received the standard immunosuppression regimen including CNIs, mycophenolate mofetil, and corticosteroids. The 2 treatment groups were compared with respect to the following variables: age, gender, tumor stage by explant, grade, size, presence of vascular invasion, focality, Child's class, baseline creatinine, and warm and cold ischemic times. The 2 groups were comparable by all factors save for cold ischemic time, which was significantly longer in the CNI-treated group. Overall survival at 1 and 5 years post-OLT for patients treated with SRL was 95.5% and 78.8%, respectively. Conversely, survival in patients treated with CNIs exclusively at the same time intervals was 83% and 62%. Although there was no difference in the incidence of major complications, the SRL group experienced a modest improvement in renal function. Cumulatively, these data suggest a potential survival benefit with SRL-based therapy in patients undergoing OLT for end-stage liver disease and concomitant malignancy.

Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal.

Our center has attempted to minimize corticosteroid (CS) use in all of our orthotopic liver transplantation (OLT) recipients. Because patients with autoimmune hepatitis (AIH) typically require CSs after transplantation, we reviewed our experience in this cohort of patients to determine (1) patient outcomes including recurrent disease and (2) long-term requirements for CS use in AIH patients. From 1988 to 2006, 1102 OLTs were performed in 1032 adult patients at the University of Colorado, of whom 66 (6%) with AIH received 68 allografts. Recurrence was defined by a clinically worsening examination and histological evidence from biopsy. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Twelve potential predictors of CS discontinuation were considered: age, gender, presence of inflammatory bowel disease (IBD), type of graft (cadaver or living donor), recurrence of AIH, warm ischemia time, follow-up time (time since transplant), and immunosuppressants (cyclosporine, tacrolimus, sirolimus, azathioprine, and mycophenolate mofetil). Overall survival at 5 years was 91%. The 1- and 5-year recurrence-free survival was 88% and 59%, respectively. Risk (incidence) of recurrent AIH at 1, 3, and 5 years was 12%, 26%, and 36%, respectively. Disease recurred in 23 of 66 patients or 34.8%. Of the 23 patients who developed recurrent disease, none received a second transplant because of recurrent disease. CSs were withdrawn in 50% of patients at the time of review. Only 2 factors on multivariate analysis were strongly associated negatively with CS withdrawal: (1) an increasing dose of the immunosuppressant and (2) the presence of IBD. Controlling for these other factors, we found that recurrent disease did not strongly influence CS withdrawal. In conclusion, outcomes in AIH patients were quite favorable, and none of the patients required retransplantation for recurrent AIH. With a CS minimization approach, one-half of the patients were able to remain CS-free.

Adjustable gastric banding in a morbidly obese patient during liver transplantation.

The increase in morbidly obese (MO; BMI >35) patients requiring liver transplant has mirrored the growing prevalence of obesity in the USA. However, there is considerable debate among physicians whether these patients should undergo transplantation. This is because outcome analysis shows that long-term survival following transplant is adversely affected by complications caused by MO. To date, there is little experience treating MO in transplant patients. Sustained weight reduction in MO liver transplant recipients would likely improve long-term survival and resolve the debate over whether these patients should receive a transplant. Three investigators have described good outcomes from bariatric surgical interventions following liver transplantation. But this requires a second operation with all the attendant risks of additional surgery and anesthesia. This report details an innovative step in the care of the MO transplant recipient: the placement of a gastric band at the time of transplantation. We describe the success of the combined procedure at 6 months following transplantation.

Hepatocellular carcinoma in a noncirrhotic patient with hereditary hemochromatosis.

We report the case of a 66-year-old man with genetic hemochromatosis who was found to have hepatocellular carcinoma (HCC) in the absence of cirrhosis. This is a rare and life-threatening complication of noncirrhotic hemochromatosis that has been described only 10 times in the English literature. In addition to presenting our case, we also cite some other potential causes of HCC in noncirrhotic patients that should be clinically considered. Although the incidence of HCC in noncirrhotic hemochromatosis patients is not sufficiently high to warrant routine screening, physicians should be aware that this fatal complication may rarely occur.

Hepatic Hemodynamics and Portal Flow Modulation: The A2ALL Experience.

OBJECTIVE: A principal aim of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study was to study hepatic blood flow and effect of portal flow modulation on graft outcomes in the setting of increasing use of smaller and left lobe grafts. METHODS: Recipients of 274 living donor liver transplant were enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, including 233 (85.0%) right lobes, 40 (14.6%) left lobes, and 1 (0.5%) left lateral section. Hepatic hemodynamics were recorded after reperfusion. A total of 57 portal flow modulations were performed on 52 subjects. RESULTS: Modulation lowered portal pressure in 68% of subjects with inconsistent effects on hepatic arterial and portal flow. A higher rate of graft dysfunction was observed in modulated vs. unmodulated subjects (31% vs. 18%; P = 0.03); however, graft survival in modulated subjects was not different from unmodulated subjects at 3 years. CONCLUSIONS: These results suggest the need for a study using a prespecified portal flow modulation protocol with defined indications to better define the effects of these interventions.

Donor preoperative oxygen delivery and post-extubation hypoxia impact donation after circulatory death hypoxic cholangiopathy.

AIM: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions. METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO2, PaO2, FiO2, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O2 content was computed as [hemoglobin (gm/dL) × 1.37 (mL O2/gm) × SpO2%) + (0.003 × PaO2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin. RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O2/100 mL blood vs 16.8 ± 3.3 mL O2/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r(2) = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006). CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.