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.

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.

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.

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.

Intercurrent infection predicts mortality in patients with late hepatic artery thrombosis listed for liver retransplantation.

Liver retransplantation for late hepatic artery thrombosis (HAT) is considered the treatment of choice for select patients. Nevertheless, there is a paucity of data to aid decision making in this setting. The aims of this single-center study of patients listed for late HAT were (1) to determine variables associated with wait-list mortality, (2) to describe survival after retransplantation, and (3) to determine variables associated with mortality after retransplantation. Seventy-eight patients were diagnosed with late HAT (incidence = 3.9%). Of the 49 patients listed for retransplantation, 9 died on the waiting list and 36 were retransplanted. The estimated 1-year survival after listing for retransplantation was 53.7%. Only multidrug-resistant (MDR) bacteria-positive cultures were predictive of wait-list mortality (P = 0.01). After retransplantation, the estimated 1- and 5-year patient survival was 71.9% and 62.5%, respectively. Increasing Model for End-Stage Liver Disease score (overall P = 0.007), MDR bacteria-positive cultures (P = 0.047), and continued antibiotic therapy (P = 0.001) at the time of retransplantation were risk factors for post retransplant death. In conclusion, patients who undergo liver retransplantation for late HAT have satisfactory outcomes. However, the presence of active infection and MDR bacteria-positive cultures should be taken into account when risk stratifying such patients.

Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis.

Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the U.K. Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation.

Renal function in patients undergoing transplantation for nonalcoholic steatohepatitis cirrhosis: time to reconsider immunosuppression regimens?

Nonalcoholic fatty liver disease is an independent risk factor for chronic kidney injury (CKI), yet the impact of liver transplantation (LT) on renal function in this at-risk group is not known. We compared the post-LT renal function of patients with nonalcoholic steatohepatitis (NASH) and a matched comparison group. Forty-eight consecutive patients who underwent transplantation for NASH between 2000 and 2008 in a single UK center were compared to non-NASH patients who were matched by age, sex, Model for End-Stage Liver Disease score, and estimated glomerular filtration rate (eGFR; calculated with the Modification of Diet in Renal Disease formula). In comparison with non-NASH patients, NASH patients had a significantly lower eGFR 3 months after LT (eGFR difference = 8.85 mL/minute/1.73 m(2), 95% confidence interval = 2.93-14.77). After adjustments for the effects of the body mass index, tacrolimus levels, diabetes mellitus, hypertension, and hepatocellular carcinoma, the difference between the groups remained significant 3 months after LT (P = 0.001). These data were then analyzed at numerous time points after LT (6, 12, and 24 months), and the time did not significantly affect the difference between the groups (P = 0.17). Within 2 years, 31.2% of the NASH patients (15/48) had developed stage IIIb CKI, whereas only 8.3% of the non-NASH patients (4/48) did (P = 0.009). In conclusion, this study has identified NASH as an independent risk factor for renal dysfunction after LT. Renal-sparing immunosuppression regimens should be considered at the time of LT to reduce the development of kidney injury in NASH patients. The optimization of such regimens requires a prospective study.

Liver transplantation for erythropoietic protoporphyria in Europe.

Liver transplantation is an established lifesaving treatment for patients with severe protoporphyric liver disease, but disease recurrence in the graft occurs for the majority of recipients. Severe burn injuries may occur when protective light filters are not used with surgical luminaires. Motor neuropathy with an unclear pathogenesis is a frequent complication. We retrospectively studied 35 transplants performed for protoporphyric liver disease in 31 European patients between 1983 and 2008. Most of the patients were male (61.3%), and the mean age at the time of primary transplantation was 39 years (range = 9-60 years). The overall patient survival rates were 77% at 1 year and 66% at 5 and 10 years. The overall rate of disease recurrence in the graft was 69%. Forty-three percent of the patients experienced recurrence within a year, but this was often a transient finding that was associated with other graft complications. Phototoxic injuries due to surgical luminaires were seen in 25.0% of the patients who were not protected by filters, but these injuries were not seen in the 9 patients who were protected by filters. Significant motor neuropathies requiring prolonged ventilation complicated the postoperative course for 5 of the 31 patients (16.1%). Hematopoietic stem cell transplantation was performed for 3 patients to prevent graft loss due to disease recurrence. Prognostic markers are needed to identify patients prone to severe protoporphyric liver disease so that curative stem cell transplantation can be offered to select patients instead of liver transplantation.

Liver retransplantation in adults: a single-centre, 25-year experience.

BACKGROUND: Retransplantation is the only form of treatment for patients with irreversible graft failure. The aim of this study was to analyse a single centre's experience of the indications for and outcomes of retransplantation. METHODS: A total of 196 patients who underwent liver retransplantation using 225 grafts, between January 1982 and July 2007, were included in the study. The following parameters were analysed: patient demographics; primary diagnosis; distribution of retransplantation over different time periods; indications for retransplantation; time interval to retransplantation, and overall patient and graft survival. RESULTS: Of the 2437 primary orthotopic liver transplantations, 196 patients (8%) required a first regraft, 23 patients (1%) a second regraft and six patients (0.25%) a third regraft. Autoimmune hepatitis was the most common primary diagnosis for which retransplantation was required (12.7% of primary transplantations). The retransplantation rate declined from 12% at the beginning of our programme to 7.6% at the end of the study period. The most common indication for retransplantation was hepatic artery thrombosis (31.6%). Nearly two-thirds of the retransplantations were performed within 6 months of the primary transplantation. The 1-, 3-, 5- and 10-year patient survival rates following first retransplantation were 66%, 61%, 57% and 47%, respectively. Five-year survival after second retransplantation was 40%. None of the patients have yet survived 3 years after a third regraft. Donor age of < or =55 years and a MELD (Model for End-stage Liver Disease) score of < or =23 were associated with better outcome following retransplantation. CONCLUSIONS: First retransplantation was associated with good longterm survival. There was no survival benefit following second and third retransplantations. A MELD score of < or =23 and donor age of < or =55 years correlated with better outcome following retransplantation.

Outcomes of liver transplantation for paracetamol (acetaminophen)-induced hepatic failure.

Paracetamol (acetaminophen) hepatotoxicity, whether due to intentional overdose or therapeutic misadventure, is an indication for liver transplantation in selected cases. However, there is a concern that long-term outcomes may be compromised by associated psychopathology that may predispose patients to further episodes of self-harm or poor treatment adherence. We therefore undertook a retrospective analysis of patients transplanted for paracetamol-induced fulminant hepatic failure (FHF) to determine their long-term outcomes, psychiatric problems, and compliance and whether these issues could be predicted from pretransplant information. Records from patients undergoing liver transplantation for paracetamol-associated liver failure in this unit and 2 comparison groups (patients undergoing liver replacement for FHF from other causes and for chronic liver diseases) were examined. Of 60 patients transplanted for paracetamol-induced FHF between 1989 and 2007, 44 (73%) survived to discharge. Currently, 35 patients (58%) are surviving at an average of 9 years post-transplantation. The incidence of psychiatric disease (principally depression) and 30-day mortality were greatest in the paracetamol group, but for those who survived 30 days, there was no difference in long-term survival rates between the groups. Adherence to follow-up appointments and compliance with immunosuppression were lowest in the paracetamol overdose group. Poor adherence was not predicted by any identifiable premorbid psychiatric conditions. Two patients grafted for paracetamol FHF died from self-harm (1 from suicide and 1 from alcoholic liver disease after 5 years). This study suggests that, notwithstanding the shortage of donor liver grafts, transplantation is an appropriate therapy in selected patients, although close follow-up is indicated.

Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation.

BACKGROUND: Causes of severe cholestasis after liver transplantation (LT) are multi-factorial. Although the etiology is predictable in some, others culminate in graft/patient loss without a definitive cause identified. Severe cholestasis is usually associated with overlapped histological findings of rejection and biliary features, and diagnostic interpretation may pose a challenge. METHODS: This is 10-year retrospective analysis of patients with unexplained severe cholestasis resulting in death/graft loss within 90 days of LT. Of 1 583 LT during the study period, 90-day graft failure occurred in 129 (8%) cases; a total of 45 (3%) patients had unresolving severe cholestasis (bilirubin, >100 µmol/L; alkaline phosphatase, >400 UI/L after 15 days from LT), excluding those due to primary nonfunction/sepsis/vascular causes (n = 84). Demographics, allograft biopsies, radiological investigations, and clinical outcome were analyzed. RESULTS: All patients had persistent abnormal liver biochemistry. Doppler ultrasound scan was normal in all cases. Thirty-five (78%) recipients had at least 1 allograft biopsy (2 [1-9]). On the first biopsy, 22 (63%) patients had acute rejection, 4 (18%) early-chronic rejection, 12 (34%) antibody-mediated rejection. In subsequent biopsies chronic rejection was evident in 5 (14%) cases. Donor-specific antibodies were detected in all patients tested. Biliary anatomy was studied in detail in 9 (20%) patients, all presenting biliary strictures. The majority (n = 39; 87%) died within 32 (10-91) days, only survivors were from retransplantation (n = 3;6.5%) and biliary intervention (n = 3;6.5%). CONCLUSIONS: Unresolving severe cholestasis after LT is a key parameter predicting patient/allograft outcome. Histologically, rejection seems to overlap with biliary strictures; hence, allograft biopsy with signs of rejection should not be a reason to overlook biliary problems, in particular when biliary features are present. Only extensive radiological investigation/intervention or retransplantation prevents patient/allograft loss.

Revascularization Time in Liver Transplantation: Independent Prediction of Inferior Short- and Long-term Outcomes by Prolonged Graft Implantation.

BACKGROUND: Strategies for successful transplantation are much needed in the era of organ shortage, and there has been a resurgence of interest on the impact of revascularization time (RT) on outcomes in liver transplantation (LT). METHODS: All primary LT performed in Birmingham between 2009 and 2014 (n = 678) with portal reperfusion first were stratified according to RT (<44 minutes vs ≥44 minutes) and graft quality (standard liver graft [SLG], Donor Risk Index < 2.3 vs marginal liver graft [MLG], Donor Risk Index ≥ 2.3). RESULTS: Revascularization time of 44 minutes or longer resulted in significantly greater incidence of early allograft dysfunction (EAD) (29% vs 47%, P < 0.001), posttransplant acute kidney injury (AKI) (39% vs 60%, P < 0.001), and new-onset AKI (37% vs 56%, P < 0.001), along with poor long-term outcome (3-year graft survival 92% vs 83%, P = 0.001; 3-year patient survival 87% vs 79%, P = 0.004). On multivariable analysis, RT ≥ 44 was a significant independent predictor of EAD, renal dysfunction, and overall graft survival, but not patient survival. The cumulative effect of prolonged revascularization in marginal grafts (MLG) resulted in the worst transplant outcome compared with all other groups, which could be mitigated by rapid revascularization (SLG, SLG, MLG vs MLG; EAD 24%, 39%, 39% vs 69%; AKI 32%, 46%, 51% vs 70%; 3-year graft survival 94%, 87%, 88% vs 70%, respectively; each P < 0.001). Factors associated with lack of abdominal space, larger grafts, and surgical skills were predictive of RT ≥ 44. CONCLUSIONS: Shorter graft revascularization is a protective factor in LT, particularly in the setting of graft marginality. Careful graft-recipient matching and emphasis on surgical expertise may aid in achieving better outcomes in LT.