Severe Cholestasis Predicts Recurrent Primary Sclerosing Cholangitis Following Liver Transplantation.

BACKGROUND AIMS: Primary sclerosing cholangitis (PSC) may reoccur following liver transplantation (LT) and the diagnosis established once imaging studies demonstrate the diagnostic cholangiographic appearance. To evaluate whether the development of recurrent PSC (rPSC) is associated with cholestasis soon after LT, we studied whether changes in hepatic biochemistry within the first 12 months were linked with the development of rPSC and graft loss. METHODS: We conducted a retrospective cohort analysis of 158 transplant recipients with PSC in Canada, and 549 PSC transplant recipients from the United Kingdom. We evaluated serum liver tests within 12 months after LT and the subsequent development of a cholangiographic diagnosis of rPSC as a time-dependent covariate using Cox regression. Severe cholestasis was defined as either alkaline phosphatase> 3xupper limit of normal or total bilirubin> 100 µmol/L. RESULTS: Patients who developed rPSC were more likely to have severe cholestasis versus those without at 3 months (20.5% vs 8.2%, p=0.011), at 6 months (17.9% vs. 10.0%, p=0.026) and 12 months (15.4% vs. 7.8%, p=0.051) in the Canadian cohort and at 12 months in the UK cohort (27.9% vs. 12.6%, p<0.0001). By multivariable analysis, development of severe cholestasis in the Canadian cohort at 3 months (HR=2.41, p=0.046) and in the UK cohort at 12 months (HR=3.141, p<0.0001) were both associated with rPSC. Severe cholestasis at 3 months in the Canadian cohort was predictive of graft loss (HR=3.88, p=0.0001). CONCLUSIONS: The development of cholestasis within 3 to 12 months following LT was predictive of rPSC and graft loss.

Antibodies to gp210 and understanding risk in patients with primary biliary cholangitis.

BACKGROUND AND AIMS: A variety of auto-antibody assays are available as part of the clinical care of patients with liver disease. We sought to better understand the clinical utility of immune serological testing in patients with primary biliary cholangitis (PBC). METHODS: We retrospectively analysed data from 2846 patients investigated for liver disease at a UK liver centre between 2001 and 2017. A total of 499 patients with PBC were identified. Immune serology results were examined for their diagnostic utility and prognostic significance to predict transplant-free survival. RESULTS: Antimitochondrial antibodies (AMAs) were specific (94.5%) and sensitive (85.6%) for PBC; antinuclear antibodies (ANAs) against glycoprotein 210 (gp210) and sp100 were specific (>98%) but not sensitive (<25%). The disease-specific ANAs were detectable in 29.6% of AMA-negative patients. Anti-gp210 auto-antibodies were significantly associated with elevated serum aminotransferase activity, bilirubin and liver stiffness at presentation (P < .010). Anti-gp210 auto-antibodies predicted non-response to ursodeoxycholic acid (UDCA) by GLOBE criteria (39.3% vs 16.7%, P = .005). Moreover, anti-gp210 was independently associated with death or liver transplantation (HR 3.22, 95% CI 1.49-6.96; P = .003), after accounting for other significant baseline determinants of outcome. Serologic finding of anti-gp210 antibodies conferred an independent risk of death or transplantation (HR 4.13, 95% CI 1.85-9.22; P = .001) after accounting for treatment response. CONCLUSION: In our single-centre cohort of patients with PBC, the presence of anti-gp210 was associated with an adverse presenting phenotype, predicted treatment non-response and independently predicted reduced transplant-free survival.

What did the European Liver Transplant Registry bring to liver transplantation?

Since its foundation in 1985, the European Liver Transplant Registry has evolved to become an important tool to monitor the liver transplantation activity in Europe. The vast amount of data collected on 169 473 liver transplantations performed in 153 238 recipients has also resulted in scientific publications. Without doubt, several of these have influenced the daily practice of liver transplantation. This paper gives an overview of the development, the functioning, and the scientific activity of the European Liver Transplant Registry during more than three decades. Indeed, it can be said that the registry helped to advance the practice of liver transplantation not only in Europe but also worldwide.

Outcomes of Pregnancy in Recipients of Liver Transplants.

BACKGROUND & AIMS: Despite increasing reports of pregnancy in women who received liver transplants, it is not clear how transplantation and immunosuppression affect pregnancy. We collected data from liver transplant recipients who became pregnant on immunosuppression regimens, pregnancy management, graft morbidity, and outcomes of mothers and neonates. METHODS: We searched the liver transplant database in Birmingham, United Kingdom, for women who reported pregnancy after liver transplantation from August 1986 through May 2016. We collected information on morbidities and outcomes of 139 pregnancies in 83 women (median age at conception, 27 y; range, 15-46 y). Fisher exact tests were used to compare categoric variables and Mann-Whitney U and Kruskal-Wallis tests were used to compare continuous variables. The primary outcome was the live birth rate in the entire cohort. Additional outcomes analyzed included differences in immunotherapy regimens, and outcomes associated with exposure to cyclosporine and tacrolimus, time to transplantation (<12 vs >12 mo), and time period of pregnancy (1986-2000 vs 2001-2016). RESULTS: Of the pregnancies, 69% resulted in live births, 19% resulted in miscarriages or still births, and 9% were terminated. A higher proportion of patients who conceived more than 1 year after liver transplantation had live births than of women who conceived before this time (98% vs 80%; P = .006). Tacrolimus exposure was associated with higher risks of premature delivery (P = .045) and caesarian section (P = .031) than cyclosporine exposure. Compared with the period from 1986 to 2000, women who conceived from 2001 to 2016 had a significantly shorter time between transplantation and conception (median, 3 vs 7 y; P = .027), frequent use of tacrolimus vs cyclosporine (84% vs 26%; P = .001), and a higher incidence of cesarean section (44% vs 32%; P = .025). CONCLUSIONS: Almost 70% of women who conceive after liver transplantation have live births, although this rate is lower than that of women in the overall population. These cases require involvement of hepatologists and obstetricians.

Incidence and outcome of colorectal cancer in liver transplant recipients: A national, multicentre analysis on 8115 patients.

BACKGROUND & AIMS: De novo malignancies after liver transplantation represent one of the leading causes of death in the long-term. It remains unclear whether liver transplant recipients have an increased risk of colorectal cancer and whether this negatively impacts on survival, particularly in those patients affected by primary sclerosing cholangitis and ulcerative colitis. METHODS: In this national multicentre cohort retrospective study, the incidence of colorectal cancer in 8115 evaluable adult patients undergoing a liver transplantation between 1 January 1990 and 31 December 2010 was compared to the incidence in the general population through standardised incidence ratios. RESULTS: Fifty-two (0.6%) cases of colorectal cancer were identified at a median of 5.6 years postliver transplantation, predominantly grade 2 (76.9%) and stage T3 (50%) at diagnosis. The incidence rate of colorectal cancer in the whole liver transplant population was similar to the general UK population (SIR: 0.92), but significantly higher (SIR: 7.0) in the group of patients affected by primary sclerosing cholangitis/ulcerative colitis. One-, five- and ten-year survival rates from colorectal cancer diagnosis were 71%, 48% and 31%, respectively, and the majority of colorectal cancer patients died of cancer-specific causes. CONCLUSIONS: Liver transplantation alone is not associated with an increased risk of colorectal cancer development. The primary sclerosing cholangitis/ulcerative colitis liver transplant population showed a significantly higher risk of colorectal cancer development than the general population, with a high proportion of advanced stage at diagnosis and a reduced patient survival.

Clinical outcomes of donation after circulatory death liver transplantation in primary sclerosing cholangitis.

BACKGROUND & AIM: Primary sclerosing cholangitis (PSC) is a progressive fibro-inflammatory cholangiopathy for which liver transplantation is the only life-extending intervention. These patients may benefit from accepting liver donation after circulatory death (DCD), however their subsequent outcome is unknown. The aim of this study was to determine the clinical impact of using DCD liver grafts in patients specifically undergoing transplantation for PSC. METHODS: Clinical outcomes were prospectively evaluated in PSC patients undergoing transplantation from 2006 to 2016 stratified by donor type (DCD, n=35 vs. donation after brainstem death [DBD], n=108). RESULTS: In liver transplantation for PSC; operating time, days requiring critical care support, total ventilator days, incidence of acute kidney injury, need for renal replacement therapy (RRT) or total days requiring RRT were not significantly different between DCD vs. DBD recipients. Although the incidence of ischaemic-type biliary lesions was greater in the DCD group (incidence rate [IR]: 4.4 vs. 0 cases/100-patient-years; p<0.001) there was no increased risk of post-transplant biliary strictures overall (hazard ratio [HR]: 1.20, 0.58-2.46; p=0.624), or in sub-analysis specific to anastomotic strictures or recurrent PSC, between donor types. Graft loss and mortality rates were not significantly different following transplantation with DCD vs. DBD livers (IR: 3.6 vs. 3.1 cases/100-patient-years, p=0.34; and 3.9 vs. 4.7, p=0.6; respectively). DCD liver transplantation in PSC did not impart a heightened risk of graft loss (HR: 1.69, 0.58-4.95, p=0.341) or patient mortality (0.75, 0.25-2.21, p=0.598). CONCLUSION: Transplantation with DCD (vs. DBD) livers in PSC patients does not impact graft loss or patient survival. In an era of organ shortage, DCD grafts represent a viable therapeutic option for liver transplantation in PSC patients. Lay summary: This study examines the impact of liver transplantation in primary sclerosing cholangitis (PSC) with organs donated after circulatory death (DCD), compared to donation after brainstem death (DBD). We show that in appropriately selected patients, the outcomes for DCD transplantation mirror those using DBD livers, with no significant differences in complication rate, patient survival or transplanted liver survival. In an era of organ shortage and increasing wait-list times, DCD livers represent a potential treatment option for transplantation in PSC.

Longterm corticosteroid use after liver transplantation for autoimmune hepatitis is safe and associated with a lower incidence of recurrent disease.

Patients transplanted for autoimmune hepatitis (AIH) are at risk of recurrent disease. Our current practice is to maintain long-term low-dose corticosteroids with additional immunosuppressive agents. This study describes the implications on patients' outcomes, sepsis, and osteoporosis. We collected data on patients transplanted between January 1999 and October 2014 in a single center who survived for more than 6 months. AIH recurrence was diagnosed by a combination of histology, raised immunoglobulin G levels, and exclusion of other etiologies. Sepsis was defined as any infection that resulted in significant morbidity or mortality. Osteoporosis was defined as a bone densitometry T score of less than -2.0 or evidence of osteoporosis-related fractures. Outcomes were assessed using Kaplan-Meier survival analysis methods. Seventy-three AIH patients underwent liver transplantation with a median follow-up of 94 months (interquartile range, 55-144). The cohort was mainly Caucasian (78%), female (79%), with type 1 AIH (90%), and a mean age of 43 ± 15 years. Overall survival was 92%, 90%, 86%, and 73%, and regraft-free survival was 86%, 81%, 78%, and 64% at 1, 3, 5, and 10 years, respectively. Five patients developed AIH recurrence, giving recurrence rates of 0%, 4%, 6%, and 11% at 1, 3, 5, and 10 years, respectively. Pneumonia was the most common infection, but gastroenteritis and cholangitis were the most recurrent. Freedom from sepsis was 91%, 82%, 80%, and 63%, and freedom from osteoporosis was 100%, 94%, 82%, and 58% at 1, 3, 5, and 10 years, respectively. Longterm low-dose corticosteroid in combination with other immunosuppressive agents seems to reduce AIH recurrence without jeopardizing patient and graft survival. Sepsis and osteoporosis did not occur more often compared to the published literature on liver transplant recipients.

The new liver allocation score for transplantation is validated and improved transplant survival benefit in Germany but not in the United Kingdom.

Prognostic models for the prediction of 90-day mortality after transplantation with pretransplant donor and recipient variables are needed to calculate transplant benefit. Transplants in adult recipients in Germany (Hannover, n = 770; Kiel, n = 234) and the United Kingdom (Birmingham, n = 829) were used for prognostic model design and validation in separate training and validation cohorts. The survival benefit of transplantation was estimated by subtracting the observed posttransplant 90-day mortality from the expected 90-day mortality without transplantation determined by the Model for End-Stage Liver Disease (MELD) score. A prognostic model called the liver allocation score (LivAS) was derived using a randomized sample from Hannover using pretransplant donor and recipient variables. This model could be validated in the German training and validation cohorts (area under the receiver operating characteristic curve [AUROC] > 0.70) but not in the English cohort (AUROC, 0.58). Although 90-day mortality rates after transplantation were 13.7% in Hannover, 12.1% in Kiel, and 8.3% in Birmingham, the calculated 90-day survival benefits of transplantation were 6.8% in Hannover, 7.8% in Kiel, and 2.8% in Birmingham. Deployment of the LivAS for limiting allocation to donor and recipient combinations with likely 90-day survival as indicated by pretransplant LivAS values below the cutoff value would have increased the survival benefit to 12.9% in the German cohorts, whereas this would have decreased the benefit in England to 1.3%. The English and German cohorts revealed significant differences in 21 of 28 pretransplant variables. In conclusion, the LivAS could be validated in Germany and may improve German allocation policies leading to greater survival benefits, whereas validation failed in England due to profound differences in the selection criteria for liver transplantation. This study suggests the need for national prognostic models. Even though the German centers had higher rates of 90-day mortality, estimated survival benefits were greater. Liver Transplantation 22 743-756 2016 AASLD.

Accepting multiple simultaneous liver offers does not negatively impact transplant outcomes.

Impact of performing multiple liver transplants (LT) in a short period of time is unknown. Consecutively performed LT potentially increase complication rates through team fatigue and overutilization of resources and increase ischemia time. We analyzed the impact of undertaking consecutive LT (Consecutive liver transplant, CLT; LT preceded by another transplant performed not more than 12 h before, both transplants grouped together) on outcomes. Of 1702 LT performed, 314 (18.4%) were CLT. Outcome data was compared with solitary LT (SLT; not more than one LT in 12-h period). Recipient, donor, and graft characteristics were evenly matched between SLT and CLT; second LT of CLT group utilized younger donors grafts with longer cold ischemic times (P = 0.015). Implantation and operative time were significantly lower in CLT recipients on intergroup analysis (P = 0.0001 and 0.002, respectively). Early hepatic artery thrombosis (E-HAT) was higher in CLT versus SLT (P = 0.038), despite absolute number of E-HAT being low in all groups. Intragroup analysis demonstrated a trend toward more frequent E-HAT in first LT, compared to subsequent transplants; however, difference did not reach statistical significance (P = 0.135). In era of organ scarcity, CLT performed at high-volume center is safe and allows pragmatic utilization of organs, potentially reducing number of discarded grafts and reducing waiting list mortality.

Long-term follow-up after endovascular treatment of hepatic venous outflow obstruction following liver transplantation.

Hepatic venous outflow obstruction (HVOO) is a rare complication after liver transplantation (LT) associated with significant morbidity and reduced graft survival. Endovascular intervention has become the first-line treatment for HVOO, but data on long-term outcomes are lacking. We have analysed outcomes after endovascular intervention for HVOO in 905 consecutive patients who received 965 full-size LT at our unit from January 2007 to June 2014. There were 27 (3%) patients who underwent hepatic venogram for suspected HVOO, with persistent ascites being the most common symptom triggering the investigation (n = 19, 70%). Of those, only 10 patients demonstrated either stricture or pressure gradient over 10 mmHg on venogram, which represents a 1% incidence of HVOO. The endovascular interventions were balloon dilatation (n = 3), hepatic vein stenting (n = 4) and stenting with dilatation (n = 3). Two patients required restenting due to stent migration. The symptoms of HVOO completely resolved in all but one patient, with a median follow-up period of 74 (interquartile range 39-89) months. There were no procedure-related complications or mortality. In conclusion, the incidence of HVOO in patients receiving full-size LT is currently very low. Endovascular intervention is an effective and safe procedure providing symptom relief with long-lasting primary patency.

Non-selective ß-blockers are associated with improved survival in patients with ascites listed for liver transplantation.

OBJECTIVE: Recent data have suggested that non-selective ß-blockers (NSBB) are associated with increased mortality in patients with cirrhosis and refractory ascites. However, other evidence implies that NSBB may be beneficial in this setting by reducing bacterial translocation. Our aim was to determine whether NSBB use was a risk factor for mortality in patients with end-stage chronic liver disease and ascites awaiting liver transplantation. DESIGN: This was a single-centre retrospective study of 322 patients with ascites listed January 2007 to July 2011. RESULTS: NSBB patients (n=159) and non-NSBB patients (n=163) were comparable with regards to listing model for end-stage liver disease score (p=0.168), frequency of hepatocellular carcinoma (p=0.193) and refractory ascites (35.2% vs. 37.4%, p=0.681). 82 patients died, 221 patients were transplanted and 19 patients were removed from the list during a median follow-up duration of 72 days; the median time to death was 150 and 54 days in the NSBB and non-NSBB groups, respectively. In a multivariate competing risk Cox model, patients on NSBB had reduced mortality compared with propensity risk score-matched non-NSBB patients (HR 0.55; 95% CI 0.32 to 0.95, p=0.032). Similarly, in the subgroup of patients with refractory ascites (n=117), NSBB remained independently associated with less waitlist death (adjusted HR 0.35; 95% CI 0.14 to 0.86, p=0.022). CONCLUSIONS: NSBB in patients with ascites and refractory ascites listed for liver transplantation are not detrimental, and instead are associated with reduced waitlist death. Our findings argue that NSBB are safe and may confer benefit in patients with ascites complicating end-stage liver disease.

Risk factors for recurrent primary sclerosing cholangitis after liver transplantation.

BACKGROUND & AIMS: The association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is well recognised. However, the relationship between IBD and recurrent PSC (rPSC) is less well understood. We assessed the prevalence of rPSC and analysed the factors associated with rPSC post-liver transplantation and its influence on graft and patient survival. METHODS: This is a UK multicentre observational cohort study across six of the seven national liver transplant units. All patients undergoing a first liver transplant for PSC between January 1 1990 and December 31 2010 were included. Prospectively collected liver transplant data was obtained from NHSBT and colitis data was retrospectively collected from individual units. RESULTS: There were 679 (8.8%) first transplants for PSC. 347 patients (61.4%) had IBD, of which 306 (88.2%) had ulcerative colitis (UC). 81 (14.3%) patients developed rPSC and 37 (48.7%) of them developed graft failure from rPSC. Presence of UC post-liver transplant (HR=2.40, 95% CI 1.44-4.02) and younger age (HR=0.78, 95% CI 0.66-0.93) were the only factors significantly associated with rPSC. rPSC was associated with over a 4-fold increase in the risk of death (HR=4.71, 95% CI 3.39, 6.56) with 1, 5, and 10-year graft survival rates of 98%, 84%, and 56% respectively compared to 95%, 88%, and 72% in patients who did not develop rPSC. CONCLUSION: The presence of UC post-liver transplant is associated with a significantly increased risk of rPSC. Furthermore, the presence of rPSC increases the rate of graft failure and death, with higher re-transplantation rates.

Vasculobiliary complications following adult right lobe split liver transplantation from the perspective of reconstruction techniques.

Split liver transplantation (SLT) compensates for the organ shortage and provides an alternative solution for recipients disadvantaged by a smaller body size. Variations in the hepatic arterial anatomy and reconstructive techniques may lead to more technical complications, and we sought to analyze the incidence and risk factors of vasculobiliary complications with respect to reconstructive techniques. We identified 171 adult right lobe SLT procedures and 1412 whole liver transplantation (WLT) procedures between January 2000 and June 2012 and compared the results of these 2 groups. In the SLT group, arterial reconstruction techniques were classified into 4 subgroups (I-IV), and biliary reconstruction was classified into 2 groups [duct-to-duct (DD) anastomosis and Roux-en-Y hepaticojejunostomy (RH)]. Specific surgical complications were analyzed against reconstruction techniques. The overall incidence of vascular and biliary complications in the SLT group was greater than that in the WLT group (P = 0.009 and P = 0.001, respectively). There was no difference in hepatic artery thrombosis (HAT), but we saw a tendency toward early HAT in the presence of multiple hepatic arteries supplying the right lobe graft (group IV; 20%) in comparison with the other arterial reconstruction groups (P = 0.052). No difference was noticed in the overall incidence of biliary complications in either DD or RH recipients across 4 arterial reconstruction groups. When the arterial reconstruction involved a right hepatic artery (groups II and III) combined with a DD biliary anastomosis, there was a significant preponderance of biliary complications (P = 0.04 and P = 0.01, respectively). There was no survival difference between SLT and WLT grafts. In conclusion, the complications of SLT are directly related to arterial and biliary reconstruction techniques, and this classification helps to identify high-risk reconstructive techniques.

Neutrophil-to-lymphocyte ratio predicts mortality in patients listed for liver transplantation.

BACKGROUND & AIMS: In the absence of overt infection, the systemic inflammatory response is increasingly recognised as a pathogenetic factor in the circulatory dysfunction of advanced cirrhosis. Our aim was to determine whether the neutrophil-to-lymphocyte ratio, a marker of systemic inflammation, is predictive of mortality in patients with end-stage cirrhosis listed for liver transplantation. METHODS: A single centre study of 570 patients listed for first elective single-organ liver transplantation January 2007-June 2011. RESULTS: The median listing neutrophil-to-lymphocyte ratio was 2.9 (IQR 1.9-4.7). Neutrophil-to-lymphocyte ratio demonstrated a positive correlation with listing serum bilirubin (P < 0.001), negative correlation with serum sodium (P < 0.001), and positive correlation with the MELD score (P < 0.001). Neutrophil-to-lymphocyte ratio increased with increasing severity of ascites (P < 0.001). A higher neutrophil count (P < 0.001) and lower lymphocyte count (P = 0.001) were predictors of wait-list death. In a multivariate competing risk Cox model, neutrophil-to-lymphocyte ratio remained independently associated with mortality (HR 1.10; 95% CI 1.05-1.15, P < 0.001). The proportion of patients with a neutrophil-to-lymphocyte ratio <2, 2-4.9, and ≥5 who had died by 3 months of listing was 3%, 13.8% and 37.3% respectively (P < 0.001). After adjusting for MELD, increasing increments of neutrophil-to-lymphocyte ratio were predictive of death by 3 months (P = 0.043). CONCLUSIONS: The blood neutrophil-to-lymphocyte ratio, a simple and readily available marker of systemic inflammation, is an independent predictor of mortality in patients with liver failure listed for liver transplantation.

The evolving use of higher risk grafts is associated with an increased incidence of acute kidney injury after liver transplantation.

BACKGROUND & AIMS: The growing discrepancy between supply and demand for liver transplantation has necessitated a greater use of higher risk grafts. Donation after Circulatory Death (DCD) liver transplant recipients have an increased frequency of acute kidney injury (AKI). We hypothesised that other higher risk grafts might also impact negatively on renal function. Our aim was to examine the effect of the evolving use of higher risk grafts on the incidence of post liver transplant AKI. METHODS: Single-centre study of 1152 patients undergoing first-single-organ liver transplantation for chronic liver disease 01/2000-12/2011. To assess the impact of the evolution of graft quality over time; donor/graft/recipient variables were compared over three 4-year periods. RESULTS: Pretransplant recipient renal function improved during follow-up (p<0.001), and the median postoperative day-1 (p<0.001), -2 (p<0.001), and -3 (p<0.001) tacrolimus trough levels fell. The proportion of patients receiving a higher risk graft was 31.8% in 2000-2003, 40.9% in 2004-2007, and 59.1% in 2008-2011 (p<0.001). There was a progressive increase in AKI (2000-2003, OR 1.00; 2004-2007, OR 1.43; 2008-2011, OR 2.40, p<0.001). After adjusting for recipient variables increasing recipient warm ischaemic time (p=0.019), DCD transplantation (p<0.001), donor age ≥60 years (p=0.020), and donor body mass index ≥30 kg/m(2) (p<0.001) were independent predictors of AKI. CONCLUSIONS: The increasing use of higher risk liver grafts is associated with an increased incidence of AKI. These findings support the need for therapies that minimise the hepatic ischaemia-reperfusion injury.

Etiology and management of hepatic artery thrombosis after adult liver transplantation.

Hepatic artery thrombosis (HAT) represents a major cause of graft loss and mortality after liver transplantation. It occurs in up to 9% of adult recipients. The early diagnosis of HAT decreases septic complications, multiorgan failure, and graft loss, and there are better outcomes after treatment. In this study, we reviewed 102 episodes of HAT, which were classified as early hepatic artery thrombosis (E-HAT) when they were diagnosed within the first 21 days after transplantation. The overall incidence of HAT was 7%: 31 episodes (30.4%) were identified as E-HAT, and 71 episodes (69.6%) were identified as late hepatic artery thrombosis (L-HAT). Graft dysfunction was the commonest presentation (30 cases or 29%). Most E-HAT cases were managed with retransplantation (74%), whereas early revascularization was carried out for only 13% with a 75% success rate. The incidence of retransplantation for L-HAT was only 41%, whereas 32% were too ill for relisting and eventually died. Successful conservative management was noted for 13 of the 102 patients (13%) with collateralization and good hepatic perfusion, with biliary complications encountered in 7 cases (54%) subsequently. A multivariate analysis showed that previous episodes of HAT, the number of arterial anastomoses, and a low donor weight were independent risk factors for E-HAT, whereas a history of upper abdominal operations (non-HAT), a previous history of HAT, a low donor weight, and a recipient age < 50 years were independent risk factors for L-HAT. The graft survival rates for HAT patients were 52%, 36.6%, and 27.4% at 1, 3, and 5 years, whereas the corresponding rates were 81.4%, 81.2%, and 76.4% for non-HAT patients. In conclusion, prompt revascularization for E-HAT patients decreases the incidence of serious, irreversible septic complications and graft loss and improves overall outcomes. A significant number of L-HAT patients do not require further intervention despite the high incidence of ischemic cholangiopathy.

Increasing the donor pool: consideration of prehospital cardiac arrest in controlled donation after circulatory death for liver transplantation.

Donor warm ischemia has implications for outcomes after liver transplantation (LT) using organs from donation after circulatory death (DCD) donors. Prehospital cardiac arrest (PHCA) before donation may generate a further ischemic insult. The aim of this single-center study of 108 consecutive DCD LT procedures was to compare the outcomes of PHCA and non-PHCA cohorts. A review of a prospectively collected database of all DCD grafts transplanted between January 2007 and October 2011 was undertaken to identify donors who had sustained PHCA. The unit policy was to consider such donors when transaminase levels were ≤4 times the normal range and had an improving trend. Twenty-six of the 108 DCD transplants were from DCD donors with PHCA, and 82 were in the non-PHCA cohort. A comparative analysis of the PHCA and non-PHCA cohorts showed better short-term results (a low incidence of acute kidney injury) for the PHCA group but satisfactory long-term results for both groups with no significant differences in graft or patient survival between them. In conclusion, a careful donor selection policy for including PHCA DCD donors with normalized liver function tests or transaminase levels ≤ 4 times the norm resulted in successful transplantation and could boost the donor pool with no adverse outcomes.

Split liver transplant recipients do not have an increased frequency of acute kidney injury.

Small series have suggested that split liver transplantation (SLT) has an increased frequency of peri-operative acute kidney injury (AKI). However, the optimal donor selection in this setting could have a favourable impact on renal outcomes. This was a retrospective single-centre study of 76 adults who underwent SLT (right extended lobe) and 301 adults who underwent elective full-size donation after brain death liver transplantation (FSLT). SLT recipients were less likely than unmatched FSLT recipients to develop AKI (≥stage 1 KDIGO criteria) (40.3% vs. 56.1%, P = 0.016) and had a reduced frequency of renal replacement therapy (11.8% vs. 21.9%, P = 0.049). In 72 pairs of SLT patients and propensity risk score-matched FSLT controls the incidence of AKI was not significantly different (40.3% vs. 47.2%, P = 0.473). However, SLT patients were less likely to require renal replacement therapy (11.1% vs. 23.6%, P = 0.078; adjusted OR 0.32; 95% CI 0.11-0.87, P = 0.026). There was no association between SLT and the development of chronic kidney disease (eGFR<60 ml/min/1.73 m(2) , log rank P = 0.534). In conclusion, SLT is not associated with an increased frequency of AKI. These observations support the postulation that the optimal donor status of SLT may result in less graft injury with renal sparing effects.

Quantification of polyclonal free light chains in clinical samples using a single turbidimetric immunoassay.

BACKGROUND: Elevated polyclonal serum free light chain (FLC) levels have been associated with increased mortality and disease activity in many conditions. Currently, polyclonal FLC quantification requires summation of individual FLCκ and FLCλ assays. Here we present a single assay for combined FLC (cFLC, Combylite) which reduces assay time and eliminates potential imprecision errors incurred by summating FLC assays (ΣFLC). METHODS: Sheep FLCκ- and FLCλ-specific antibodies were conjugated to latex microparticles to quantify FLCκ and FLCλ in a single assay. Combylite results were compared to ΣFLC (Freelite) in 132 healthy controls and 1127 patient samples. The utility of cFLC for predicting all-cause mortality in a haematological referral population was evaluated. RESULTS: cFLC and ΣFLC results were highly concordant (Passing-Bablok equation y=0.98x-1.59 mg/L, R²=0.96). Combylite assay imprecision was low at concentrations around the upper normal range [coefficient of variation (CV) 5.5%, 54 mg/L] and the upper limit of the measuring range (CV 5.5%, 170 mg/L). cFLC levels were significantly raised in disease states compared with healthy controls. Additionally, cFLC >65 mg/L was associated with shorter overall survival in a haematological referral population (hazard ratio=4.5, p<0.001). CONCLUSIONS: cFLC values obtained using Combylite were comparable to ΣFLC results over a wide concentration range, were elevated in diseases characterised by B cell activation and were associated with increased mortality in a haematological referral population. These observations indicate the Combylite assay has value for investigating the role of B cell activation in disparate disease groups and could be considered as a surrogate indication of B cell function.

Hepatic ischemia reperfusion injury is associated with acute kidney injury following donation after brain death liver transplantation.

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury (AKI). This suggests that hepatic ischemia-reperfusion injury may play a critical role in the pathogenesis of AKI after liver transplantation. The aim of this single-center study was to determine if hepatic ischemia-reperfusion injury, estimated by peak peri-operative serum amino-transferase (AST), is associated with AKI following donation after brain death (DBD) liver transplantation. A total of 296 patients received 298 DBD liver transplants from January 2007 to June 2011. The incidence of AKI was 35.9%. AKI was a risk factor for chronic kidney disease (P = 0.037) and mortality (P = 0.002). On univariate analysis, peak AST correlated with peak creatinine (P < 0.001) and peak change in creatinine from baseline (P < 0.001). Peak AST was higher in AKI patients (P < 0.001). The incidence of AKI in patients with a peak AST of <1500, 1500-2999 and ≥ 3000 U/l was 26.1%, 39.8% and 71.2%, respectively (P < 0.001). On multiple logistic regression analysis, peak AST was independently associated with the development of AKI (P < 0.001). In conclusion, hepatic ischemia-reperfusion injury demonstrates a strong relationship with peri-operative AKI in DBD liver transplant recipients.