Elective Liver Transplantation Research Articles

Validação do escore APACHE IV no transplante hepático pós‐operatório no sul do Brasil: estudo de coorte

BackgroundLiver transplantation is the only curative therapeutic modality available for individuals at end‐stage liver disease. There is no reliable method of predicting the early postoperative outcome of these patients. The Acute Physiology and Chronic Health Evaluation (APACHE) is a widely used model for predicting hospital survival and benchmarking in critically ill patients. This study evaluated the calibration and discrimination of APACHE IV in the postoperative period of elective liver transplantation in the southern Brazil. MethodsThis was a clinical prospective and unicentric cohort study that included 371 adult patients in the immediate postoperative period of elective liver transplantation from January 1, 2012 to December 31, 2016. ResultsIn this study, liver transplant patients who evolved to hospital death had a significantly higher APACHE IV score (82.7±5.1 vs. 51.0±15.8; p<0.001) and higher predicted mortality (6.5% [4.4–20.2%] vs. 2.3% [1.4–3.5%]; p<0.001). The APACHE IV score showed an adequate calibration (Hosmer‐Lemeshow – H‐L=11.37; p=0.181) and good discrimination (Receiver Operator Curve – ROC of 0.797; Confidence Interval 95% – 95% CI 0.713–0.881; p<0.0001), although Standardized Mortality Ratio (SMR=2.63), (95% CI 1.66–4.27; p<0.001) underestimate mortality. ConclusionsIn summary, the APACHE IV score showed an acceptable performance for predicting a hospital outcome in the postoperative period of elective liver transplant recipients.

Effect of anesthesia factor on kidney injury in pediatric patients undergoing living donor liver transplantation: a comparison of sevoflurane- versus propofol-based anesthesia

Objective To compare the effects of sevoflurane- and propofol-based anesthesia on kidney injury in pediatric patients undergoing living donor liver transplantation. Methods Eighty pediatric patients of both sexes, aged 5-15 months, weighing 5.5-10.0 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective living donor liver transplantation, were divided into 2 groups (n=40 each) using a random number table method: sevoflurane-based anesthesia group (group S) and propofol-based anesthesia (group P). Sevoflurane was inhaled, and the end-tidal concentration was maintained at 1.0%-3.0% in group S. Propofol 9-15 mg·kg-1·h-1 was intravenously infused in group P. Fentanyl 1-3 μg/kg was intermittently injected, and cisatracurium 1-2 μg·kg-1·min-1 was intravenously infused in two groups.Bispectral index value was maintained at 40-60.Immediately before skin incision (T1), at 30 min of anhepatic phase (T2), at 3 h of neohepatic phase (T3), at 24 h after operation (T4) and at day 3 after surgery (T5), blood samples from the central vein and urine specimens were collected for determination of the levels of neutrophil gelatinase-associated lipocalin and cystatin C in serum and urine by enzyme-linked immunosorbent assay.The urine volume, requirement for dopamine and occurrence of hypotension and myocardial ischemia were recorded during surgery. Results Compared with group P, the levels of neutrophil gelatinase-associated lipocalin and cystatin in serum and urine were significantly decreased at T3-5(P 0.05). Conclusion Compared with propofol-based anesthesia, kidney injury is attenuated in pediatric patients undergoing living donor liver transplantation under sevoflurane-based anesthesia. Key words: Acute kidney injury; Anesthetics, inhalation; Propofol; Liver transplantation; Child

Liver Transplantation in Patients with and Without Hepatocellular Carcinoma Between 1997 and 2016 in the United Kingdom: An Analysis of Changes in Short and Long-Term Post-Transplant Mortality

Background: The rising incidence of hepatocellular cancer (HCC) is increasing the demand for liver transplantation. Consequently, there have been significant changes in characteristics of donors and recipients. We evaluated short-term and long-term mortality of HCC and non-HCC recipients in successive 5-year time-periods ('eras') between 1997 and 2016. Methods: First-time single-organ elective adult liver transplant recipients were identified in a national dataset of all liver transplantations in the UK. We estimated hazard ratios (aHR) adjusted for recipient characteristics to compare mortality by era. We estimated the impact of era separately on short-term (first 90 days) and on longer-term mortality (from 90 days to 5 years). Findings: 1 879 HCC recipients and 7 661 non-HCC recipients were included. The proportion of HCC recipients increased from 13.0% (275/2117) in era 1 (1997-2001) to 23.9% (727/3042) in era 4 (2012-2016). There was an increase in use of donors following circulatory death from 0% in era 1 to 35.2% in era 4 for HCC recipients and from 0.2% to 24.1% for non-HCC recipients. 3-year mortality decreased from 28.3% in era 1 to 16.9% in era 4 (aHR: 0.47, 95%CI: 0.35-0.63) for HCC recipients and from 20.4% to 9.3% (aHR: 0.44, 0.36-0.53) for non-HCC recipients. Comparing era 1 and era 4, improvements in short-term mortality were significantly more marked than in long-term mortality both for HCC (aHR 0-90 days: 0.20, 0.10-0.39; 90 days-5 years: 0.52, 0.35-0.75; p=0.04) and for non-HCC recipients (aHR 0-90 days: 0.32, 0.24-0.42; 90 days-5 years: 0.52, 0.40-0.67; p=0.02). Interpretation: In last 20 years, mortality after liver transplantation in the UK has more than halved for HCC and non-HCC recipients, despite an increasing use of sub-optimal donor organs. Improvements in overall survival in both HCC and non-HCC recipients can be explained by decreases in short-term and in longer-term mortality. Funding Statement: National Institute of Health Research. DW is funded by a Doctoral Research Fellowship from the National Institute of Health Research. JvdM is partly supported by the NHS National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care North Thames at Bart’s Health NHS Trust. Declaration of Interests: JvdM reports grants from Healthcare Quality Improvement Partnership during the conduct of the study. All other authors declare no competing interests. Ethics Approval Statement: The study received ethics and governance approvals from the following organisations: NHS Health Research Authority’s London - Brighton & Sussex Research Ethics Committee (17/LO/0231) and NHS Health Research Authority’s Confidentiality Advisory Group (17/CAG/0025).

Validation of APACHE IV score in postoperative liver transplantation in southern Brazil: a cohort study

BackgroundLiver transplantation is the only curative therapeutic modality available for individuals at end-stage liver disease. There is no reliable method of predicting the early postoperative outcome of these patients. The Acute Physiology and Chronic Health Evaluation (APACHE) is a widely used model for predicting hospital survival and benchmarking in critically ill patients. This study evaluated the calibration and discrimination of APACHE IV in the postoperative period of elective liver transplantation in the southern Brazil. MethodsThis was a clinical prospective and unicentric cohort study that included 371 adult patients in the immediate postoperative period of elective liver transplantation from January 1, 2012 to December 31, 2016. ResultsIn this study, liver transplant patients who evolved to hospital death had a significantly higher APACHE IV score (82.7±5.1 vs. 51.0±15.8; p<0.001) and higher predicted mortality (6.5% [4.4–20.2%] vs. 2.3% [1.4–3.5%]; p<0.001). The APACHE IV score showed an adequate calibration (Hosmer-Lemeshow – H-L=11.37; p=0.181) and good discrimination (Receiver Operator Curve – ROC of 0.797; Confidence Interval 95% – 95% CI 0.713–0.881; p<0.0001), although Standardized Mortality Ratio (SMR=2.63), (95% CI 1.66–4.27; p<0.001) underestimate mortality. ConclusionsIn summary, the APACHE IV score showed an acceptable performance for predicting a hospital outcome in the postoperative period of elective liver transplant recipients.

Liver transplant listing for hepatitis C-associated cirrhosis and hepatocellular carcinoma has fallen in the United Kingdom since the introduction of direct-acting antiviral therapy.

Following the introduction of direct-acting antivirals (DAA), there have been reports of declining incidence of hepatitis C (HCV)-related liver disease as a liver transplantation indication. In this study, we assessed the impact of DAA on liver transplant indications in the UK and waiting list outcomes for patients with HCV. We assessed UK adult elective liver transplant registrants between 2006 and 2017. The aetiology of liver disease at registration was reclassified using an accepted hierarchical system and changes were assessed over time and compared before and after the introduction of DAA. Registration UKELD scores and 1-year waiting list outcomes were also compared. The proportion of waiting list patients registered with HCV-related cirrhosis reduced after the introduction of DAA from 10.5% in 2013 to 4.7% in 2016 (P<0.001). Alcohol-related liver disease (ARLD) was the leading indication for liver transplantation followed by liver cancer (26.1% and 18.4% in 2016, respectively). The proportion of registrations with Hepatocellular carcinoma (HCC) associated with HCV reduced from 46.4% in 2013 to 33.7% in 2016 (P=0.002). For patients with HCV-related cirrhosis at one year the outcomes of death, transplantation, delisting due to improvement or deterioration and awaiting a graft at 1year were similar. For patients with HCV-related HCC, the proportion dying at 1year reduced significantly from 2.9% to 0.0% (P=0.04). These data demonstrate an association between DAA and reduced listing rates for HCV-related cirrhosis and HCC, but no significant changes in waiting list outcomes other than reduced mortality in the HCC group.

Effect of dexmedetomidine on renal function in pediatric patients undergoing living donor liver transplantation

Objective To evaluate the effect of dexmedetomidine on renal function in pediatric patients undergoing living donor liver transplantation. Methods Sixty pediatric patients of both sexes with congenital biliary atresia, aged 5-15 months, weighing 5.5-10.0 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective living donor liver transplantation, were randomly divided into either control group(group C)or dexmedetomidine group(group D)with 30 patients in each group.The infants were tracheally or nasotracheally intubated and mechanically ventilated after induction of anesthesia.Dexmedetomidine was intravenously infused in a loading dose of 1 μg/kg for 10 min, followed by a continuous infusion of 0.3 μg·kg-1·h-1 until the end of operation in group D. While the equal volume of normal saline was given instead of dexmedetomidine in group C. At skin incision (T1), at 30 min of anhepatic phase (T2), at 1 h of neohepatic phase (T3), immediately after peritoneum closure (T4) and at 24 h after operation (T5), blood samples from the central vein and urine specimens were collected for determination of creatinine and blood urea nitrogen (BUN) concentrations in serum (by colorimetric assay) and β2-microglobulin (β2-MG) concentrations in serum and urine (using immunoturbidimetric method), and concentrations of tumor necrosis factor-α, interleukin-6 (IL-6) and IL-18 in serum (by enzyme-linked immunosorbent assay). The urine volume was recorded during surgery. Results Compared with group C, the urine volume was significantly increased, and the serum creatinine, BUN and β2-MG concentrations and urine β2-MG concentrations at T3-5, serum BUN concentrations at T4, 5, and serum tumor necrosis factor-α, IL-6 and IL-18 concentrations at T2-5 were decreased in group D (P<0.05). Conclusion Dexmedetomidine can improve renal function in pediatric patients undergoing living donor liver transplantation. Key words: Dexmedetomidine; Liver transplantation; Kidney

Both α-1-antitrypsin Z phenotypes and low caeruloplasmin levels are over-represented in alcohol and nonalcoholic fatty liver disease cirrhotic patients undergoing liver transplant in Ireland.

Alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD) are steatotic liver diseases and major causes of cirrhosis. Only a minority of patients with risk factors develop cirrhosis and genetic cofactors may be important in pathogenesis. Mutations in the Wilson's and α-1-antitrypsin genes are not uncommon and we speculated that they may act as cofactors. We investigated α-1-antitrypsin phenotyes and caeruloplasmin levels in patients undergoing elective liver transplantation. We compared patients with alcohol and NAFLD with nonsteatotic liver disease patients: viral hepatitis B or C, autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. Two hundred and thirty-one patients were included in the study. Pretransplant caeruloplasmin levels and α-1-antitrypsin phenotypes were available in 197 and 112 patients, respectively. α-1-Antitrypsin Z phenotypes were significantly more common in the alcohol and NAFLD group: 12/56 versus 3/56 (P<0.05). Serum caeruloplasmin (0.3±0.01 vs. 0.39±0.01 g/l, P<0.01) and serum copper levels (13.5±0.9 vs. 19.3±0.9 μmol/l, P<0.01) were significantly lower in the alcohol and NAFLD patients compared with the viral and autoimmune patients. In this study, we found the α-1-antitrypsin Z phenotype was more common, and serum caeruloplasmin and copper levels were lower in patients with fatty liver diseases. We suggest that mutations in the α-1-antitrypsin and Wilson's genes may act as cofactors in the pathogenesis of fatty liver diseases.

Liver transplantation for alcoholic hepatitis: A systematic review with meta-analysis.

BackgroundThe rate of alcohol relapse among patients who underwent liver transplantation for alcoholic hepatitis (AH) is not precisely known.AimSynthesize the available evidence on liver transplantation for AH to assess alcohol relapse and 6-month survival.MethodsMeta-analysis of trials evaluating liver transplantation for AH, either clinically severe or diagnosed on the explant.ResultsEleven studies were included. The pooled estimate rate for alcohol relapse was 0.22 (95% CI = 0.12–0.36) in overall analysis with high heterogeneity between studies (I2 = 76%), 0.20 (95% CI = 0.07–0.43) in the subgroup analysis including patients with clinically severe AH (I2 = 84%), 0.14 (95% CI = 0.08–0.23) among patients with clinically severe AH in sensitivity analysis excluding the discrepant studies that did not use stringent selection criteria for liver transplantation (I2 = 0%), and 0.15 (95% CI = 0.07–0.27) for recurrent harmful alcohol consumption among patients with clinically severe AH (I2 = 3%). The risk of alcohol relapse was not different between AH transplanted patients and patients with alcoholic cirrhosis who underwent elective liver transplantation in sensitivity analysis excluding the discrepant studies (OR = 1.68, 95%CI = 0.79–3.58, p = 0.2, I2 = 16%). The pooled estimate rate for 6-month survival was 0.85 (95% CI = 0.77–0.91, I2 = 49%), and 0.80 among patients transplanted for clinically severe AH (95% CI = 0.69–0.88, I2 = 30%). AH transplanted patients had similar 6-month survival to patients with alcoholic cirrhosis who underwent elective liver transplantation (OR = 2.00, 95% CI = 0.95–4.23, p = 0.07, I2 = 0%).ConclusionUsing stringent selection criteria, 14% of patients with clinically severe AH have alcohol relapse after liver transplantation. The percentage of alcohol relapse of AH transplanted patients is similar than that of patients who underwent elective liver transplantation.

Salvage of red blood cell units using remote electronic blood issue system in operation theater: A pilot study from India

Introduction: Anesthetists procure pre-defined number of blood units in advance for surgical patients for ‘just-in-case’ scenarios. This often results in non-usage and discarding of blood units. Blood bank discards blood units returned from operation theatre due to disruption of cold chain. In an effort to reduce this wastage an intervention from transfusion medicine team was undertaken in collaboration with liver transplant team with help of an electronically controlled remote inventory and bedside transfusion management system called BloodTrack Courier. Effectiveness of BloodTrack® Courier in tracing and reducing red cell unit wastage was studied over a four-month period and compared with four-month historical control. Materials and Method: intervention was limited to red cell units issued in elective live-donor liver transplant cases through BloodTrack (Haemonetics Corporation, USA). Controlled access linked to hospital identity cards was provided to Transfusion Medicine Specialists and Liver Transplant anesthetists with different access levels. Pre-allocated RBC units were kept at OT refrigerator for a period of 24-36 hours after which unused units were retrieved by BTS and re-inventoried. Results: Transfusion of RBC units in 60 liver transplant recipients donor before installation was compared with similar 86 liver transplant recipient-donor after installation of BloodTrack. Mean number of RBC units transfused in recipient-donor decreased from 6.2 and 1.0 unit before installation to 5.9 and 0.76 units after installation, respectively. RBC units discarded due to breakage of cold-chain reduced to zero and RBC units successfully returned to blood bank increased 7.6 times. Conclusion: Blood inventory management and remote issue function of Blood Track was very effective in saving RBC units during four-month study period.

Silybin Against Liver Ischemia-Reperfusion Injury: Something Old, Something New…

ABSTRACTIschemia reperfusion injury (IRI) is a life threatening condition that may develop after elective liver surgery or liver transplantation. Numerous surgical and pharmacological approaches have shown varying degrees of protection against liver IRI. A group of protective compounds are the flavonoids but their intestinal absorbtion and bioavailability are low and impredictible. In this issue Tsaroucha et al. reports significantly decreased hepatocellular injury, Fas/FasL expression and inhibited HMGB1 release in rats receiving a hydrosoluble, lyophilized complex of SLB and hydroxypropyl-β-cyclodextrin (SLB-HP-β-CD) intravenously.

Adult Liver Allocation in Eurotransplant.

Liver allocation in Eurotransplant is complex because allocation rules need to follow not only the guidelines of the European Commission but also the specific regulations of each of the 7 Eurotransplant countries with active liver transplant programs. Thirty-eight liver transplant centers served a population of about 135 million in 2015. Around 1600 deceased donor livers are transplanted annually. The number of deceased organ donors remains stable but donor age is increasing. Nevertheless, liver utilization rates are unchanged at around 80%. Donation after circulatory determination of death (DCD) increased fourfold in the past decade. In Belgium and the Netherlands, DCDs were responsible for 30% of deceased donor liver transplant activity in 2015; Austria only occasionally transplants a DCD liver; other Eurotransplant countries do not have active DCD programs. The most frequent indications for liver transplantation are alcoholic liver disease, hepatocellular carcinoma, and viral hepatitis. Livers are allocated first internationally to high urgency status patients or those with an approved combined organ status (for a liver in combination with heart, lung, intestine, or pancreas) and then on a national basis where allocation is recipient-driven or center-driven, depending on country-specific rules. Median waiting time for an elective liver transplant was 4,4 months in 2015; high urgency status patients waited a median of 2 days for a suitable liver. Mortality on the waiting list was 18% in 2015, 4% of patients were delisted because they became unfit for transplantation. One-year and 5-year risk unadjusted adult patient survival after transplantation is 80% and 65%, respectively.

Impact of cigarette smoking on early complications after liver transplantation: A single-center experience and a meta-analysis.

BackgroundWhile studies have shown that cigarette smoking has negative implications on the long-term outcome following liver transplantation, its role in early complications is inconclusive.MethodsThe clinical data of 162 consecutive adult patients who underwent elective liver transplantation from January, 2012 to March, 2016 were analyzed. Patients were defined as active smokers, ex-smokers, or non-smokers on the basis of documentation at the time of liver transplantation. The overall complications following liver transplantation were expressed as the comprehensive complication index (CCI). The specific complications such as the incidence of hepatic artery thrombosis, biliary complications, acute kidney injury were also assessed. A meta-analysis was carried out based on results from the present study and 11 published studies.ResultsWe found that cigarette smoking was not associated with higher CCI scores and smokers did not have a higher risk for developing hepatic artery thrombosis, biliary complications, acute kidney injury after liver transplantation. Meta-analysis confirmed the null association between cigarette smoking and an increased incidence of hepatic artery thrombosis or biliary complications in liver transplant recipients. However, the pooled results showed a significantly higher risk of cardiovascular diseases and de-novo malignancies in smokers following liver transplantation.ConclusionThere is not enough evidence supporting an association between cigarette smoking and early mortality and morbidity after liver transplantation. However, smokers should still be encouraged to quit before and after liver transplantation due to the long-term health benefits of smoking cessation.

Effect of lung-protective ventilation on acute lung injury after liver transplantation

Objective To evaluate the effects of lung-protective ventilation on acute lung injury after liver transplantation. Methods Sixty patients of both sexes, aged 21-64 yr, with body mass index of 18-28 kg/m2, of American Society of Anesthesiologists physical status Ⅱ-Ⅳ, scheduled for elective orthotopic liver transplantation, were divided into 2 groups(n=30 each)using a random number table: conventional mechanical ventilation group(group CMV)and lung-protective ventilation group(group LPV). In group LPV, the patients were mechanically ventilated(tidal volume 6-8 ml/kg, respiratory rate 10-15 breaths/min, positive end-expiratory pressure 3-10 cmH2O), and lung recruitment maneuver was performed every 2 h. Before skin incision(T1), at 3 h of preanhepatic phase(T2), at 30 min of anhepatic phase(T3)and at 2 and 4 h of neohepatic phase(T4, 5), bronchoalveolar lavage fluid(BALF)was collected and blood samples from the radial artery were simultaneously collected for determination of tumor necrosis factor-alpha and interleukin-8 concentrations in BALF and serum by enzyme-linked immunosorbent assay.At 2 h after operation(T6), before tracheal extubation(T7)and at 2 days after operation(T8), blood samples from the radial artery were collected for blood gas analysis, and oxygenation index was calculated.The concentrations of serum Clara cell secretory protein 16, surfactant protein D and soluble receptor for advanced glycation end-products were determined at T1-T8 using enzyme-linked immunosorbent assay.The postoperative emergence time, extubation time, duration of intensive care unit stay and development of acute lung injury were recorded. Results Compared with group CMV, the extubation time was significantly shortened, serum concentrations of Clara cell secretory protein 16 at T2, T3, T6 and T7, serum surfactant protein D concentrations at T5 and serum concentrations of soluable receptor for advanced glycation end-products at T5 and T6 were decreased(P 0.05). Conclusion Although lung-protective ventilation dose not decrease the development of acute lung injury after liver transplantation, it attenuates lung tissue injury to some extent. Key words: Respiration, artificial; Respiratory distress syndrome, adult; Liver transplantation

Effect of dexmedetomidine on myocardial injury in pediatric patients undergoing living-related liver transplantation

Objective To evaluate the effect of dexmedetomidine on myocardial injury in pediatric patients undergoing living-related liver transplantation. Methods Fifty-eight pediatric patients of both sexes, aged 5-20 months, weighing 4.5-15.0 kg, of American Society of Anesthesiologists physical status Ⅲ or Ⅳ, scheduled for elective living-related liver transplantation, were divided into 2 groups(n=29 each)using a random number table: control group(group C)and dexmedetomidine group(group D). In group D, dexmedetomidine was intravenously infused at a dose of 0.5 μg/kg over 10 min starting from the time point immediately before skin incision, followed by an infusion of 0.8 μg·kg-1·h-1 until the end of surgery. The equal volume of normal saline was given instead in group C. Immediately before skin incision(baseline, T0), at 10 min of anhepatic phase(T1), at 30 min of neohepatic phase(T2)and at the end of surgery(T3), blood samples were obtained from the central vein for determination of serum cardiac troponin I(cTnI), lactate dehydrogenase(LDH), alpha-hydroxybutyrate dehydrogenase(α-HBDH), interleukin-6(IL-6)and IL-10 concentrations. The changing rate of serum cTnI concentrations were calculated at T2. The occurrence of myocardial ischemia and ventricular premature beat and requirement for dopamine were recorded during surgery. Results Compared with the baseline at T0, the serum concentrations of cTnI, LDH and α-HBDH were significantly increased at T2, 3, and the serum concentrations of IL-6 and IL-10 were increased at T1-3 in both groups(P 0.05). Conclusion Dexmedetomidine can attenuate the myocardial injury to some extent in pediatric patients undergoing living-related liver transplantation. Key words: Dexmedetomidine; Liver transplantation; Child; Myocardium; Prognosis

Anaesthesia for liver transplantation

### Key points Mortality rates after liver transplantation (LT) have steadily improved in recent years as units continue to gain more experience. A prospective cohort study of 7906 liver transplants in the UK and Ireland showed an unadjusted 90 day mortality rate for first elective LT of 10.2% for the period 1994–6,1 decreasing to 3% for 2013–4.2 Seven UK centres performed 914 LT procedures during 2013–4,2 compared with 602 in 2005–6, with much of the increase occurring after a national initiative to increase donation rates.1,3 This improvement is attributed to improved surgical techniques, better recipient selection, and advances in anaesthetic and intensive care management. However, LT remains a complex undertaking—older patients, those with progressively more severe co-morbidity, and those with previous complex abdominal surgery (including previous LT) are now considered eligible. An important remaining outcome determinant is graft quality. There are three types of grafts used commonly: donation after brain death, donation after cardiac death, and living related donation (LRD). LRD, and also split liver donation where a cadaveric graft is divided for two recipients, have helped increase graft supply, but at the cost of increased complexity. LT remains the treatment of choice for end-stage liver disease (ESLD), and there is still …

Acute on Chronic Liver Failure and Urgent Orthotopic Liver Transplantation in an Adult with Alagille Syndrome

Alagille syndrome is an autosomal dominant syndrome marked by a paucity of interlobular bile ducts with cholestasis, and whose features can include butterfly vertebrae, dysmorphic facies, cardiac and ocular anomalies. Most patients are symptomatic during childhood. As adult patients may require elective liver transplant for cirrhosis and intractable pruritus, liver failure is uncommon in these patients. We present a case of liver failure in an adult with Alagille syndrome. A 32-year-old man with known Alagille syndrome was admitted to the hospital with progressive jaundice and RUQ pain. At that time his MELD was 24 and he was referred for liver transplant evaluation. A month later, he was admitted for hematemesis and hepatic encephalopathy. He had a complicated hospital course with worsening encephalopathy, hepatorenal syndrome (requiring dialysis), and septic shock due to Streptococcus viridans requiring pressors. His peak MELD score during this hospitalization was 42(total bilirubin 47.5, Cr 5, INR 2.0). A CDC high risk liver became available and he underwent an orthotopic liver transplant. This was complicated by bacterial peritonitis from an infected hematoma. However, he recovered well after treatment of his peritonitis, and LFTs were normal one month post-transplant. Allagile syndrome occurs in 1 in 70,000 live births from a JAG1 or NOTCH2 mutation. They have paucity or stenotic bile ducts with progressive cholestasis in 95%, and cirrhosis in more than 20% of cases. Initial treatment includes ursodeoxycholic acid, cholestyramine, fat soluble vitamins and nutrition support. However, 21-31% patients will require liver transplant for severe xanthomatosis, intractable pruritus, and portal hypertension. Most liver transplants are done in the pediatric group. Only 9.7% patients had their first liver transplant beyond 18 years old, and are done electively for cirrhosis and intractable pruritus. Only a few cases were reported due to acute liver failure requiring an urgent transplant, similar to our patient. Alagille syndrome patients may require liver transplantation, usually during childhood. In some cases, transplant may be required in adulthood due to liver cirrhosis and intractable pruritis, and is mostly elective. Liver failure is uncommon in these patients.

Clinical relevance of peak serum transaminases after an elective liver transplantation

Introduction: Serum transaminases are routinely monitored after liver transplantation (LT) to detect graft dysfunction. However, the role of peak-serum-transaminases (PST) on postoperative outcome is controversial. The aim of the present study was to determine whether PST was correlated early graft failure. Method: Between 2006 and 2014, 302 consecutive patients receiving a first elective liver transplant from brain-dead donor were enrolled in a single-center prospective database. Donor and recipient demographic data as well as perioperative data were recorded and retrospectively analyzed. PST was defined as the highest value of either aspartate (AST) or alanine (ALT) aminotransferase within the postoperative two days. Early graft failure was defined as death or need for retransplantation within 90-days. Multivariable analysis was performed using logistic regression models. Results: Twenty-six (8.6%) patients had graft failure, of whom 6 (23.1%) had PST >2000 UI/L. Only pre-transplant dialysis (IC 95% [1.797–24.447]; p = 0.005) and PST >2000 UI/L (IC 95% [1.484–19.130]; p = 0.010) were shown to be independent predictor of early graft failure. However the specificity and sensitivity of PST >2000 UI/L to predict early graft failure were respectively 23% and 92% and the area under the ROC curve was 0.577, indicating a low discrimination of this surrogate. Conclusion: PST is an independent predictor of early graft failure but failed to accurately detect patients who will need an early retransplantation.

Neutralizing Antibodies Against Adeno-Associated Viral Capsids in Patients with mut Methylmalonic Acidemia.

Isolated methylmalonic acidemia (MMA), a group of autosomal recessive inborn errors of metabolism, is most commonly caused by complete (mut(0)) or partial (mut(-)) deficiency of the enzyme methylmalonyl-CoA mutase (MUT). The severe metabolic instability and increased mortality experienced by many affected individuals, especially those with mut(0) MMA, has led centers to use elective liver transplantation as a treatment for these patients. We have previously demonstrated the efficacy of systemic adeno-associated viral (AAV) gene delivery as a treatment for MMA in a murine model and therefore sought to survey AAV antibody titers against serotypes 2, 8, and 9 in a group of well-characterized MMA patients, accrued via a dedicated natural history study ( clinicaltrials.gov ID: NCT00078078). Plasma samples provided by 42 patients (8 mut(-) and 34 mut(0); 10 had received organ transplantation), who ranged in age between 2 and 31 years, were analyzed to examine AAV2 (n = 35), AAV8 (n = 41), and AAV9 (n = 42) antibody titers. In total, the seroprevalence of antibodies against AAV2, AAV8, or AAV9 was 20%, 22%, and 24%, respectively. We observed a lower-than-expected seropositivity rate (titers ≥1:20) in the pediatric MMA patients (2-18 years) for both AAV2 (p < 0.05) and AAV8 (p < 0.01) neutralizing antibodies (NAbs) compared with historical controls. Those with positive NAb titers were typically older than 18 years (p < 0.05 all serotypes) or had received solid organ transplantation (p < 0.01 AAV8, AAV9). The mut(0) patients who had not been transplanted (n = 24)-that is, the subset with the greatest need for improved treatments-represented the seronegative majority, with 21 out of 24 patients lacking Abs against all AAV capsids tested. The unexpected lack of NAbs against AAV in this patient population has encouraging implications for systemic gene delivery as a treatment for mut MMA.

Subclinical spontaneous bacterial peritonitis at the time of liver transplantation does not impact on outcomes.

Liver transplant recipients are often screened for spontaneous bacterial peritonitis during the immediate preoperative evaluation to determine medical fitness to proceed. However, it is unknown whether subclinical spontaneous bacterial peritonitis impacts on post-transplant outcomes. Our aim was to determine whether subclinical spontaneous bacterial peritonitis detected at the preoperative evaluation influences the decision to proceed, and subsequent postoperative morbidity and mortality. This study is a single-centre study of 1231 adults attending for possible first elective single-organ liver transplantation between January 2000 and December 2011. A total of 434 patients underwent ascitic fluid sampling on 460 occasions. Nineteen samples fulfilled the diagnostic criteria for spontaneous bacterial peritonitis (4.8%), including one that was culture positive (Candida spp.). Patients with spontaneous bacterial peritonitis had a higher serum bilirubin level than nonspontaneous bacterial peritonitis patients (P=0.018). Out of the 19 patients, 16 (84.2%) with a positive sample proceeded to transplantation on that occasion; the ascitic microscopy result did not influence the decision to proceed in any clinically stable patient. The 30-day post-transplant survival was 93.8% for spontaneous bacterial peritonitis patients and 96.2% for nonspontaneous bacterial peritonitis patients (P=0.478). After adjusting for recipient age, UK Score for Patients with End-Stage Liver Disease (UKELD) and donor risk index, there was no association between a positive tap and death within 30 days (P=0.649). Subclinical spontaneous bacterial peritonitis is rare in patients admitted for elective liver transplantation, does not influence the decision to proceed and is not associated with increased post-transplant mortality. Our findings suggest that routine preoperative ascitic fluid sampling is not indicated in clinically stable potential transplant recipients.

Thrombin activatable fibrinolysis inhibitor as a bleeding predictor in liver transplantation: a pilot observational study

Objective To correlate the levels of thrombin activatable fibrinolysis inhibitor in the immediate postoperative period and at 24 hours postoperatively with the volume of intraoperative bleeding.Methods Twenty-one patients allocated immediately before (elective or emergency) liver transplantation were analyzed. Blood samples were collected for thrombin activatable fibrinolysis inhibitor analysis at three different time points: immediately before liver transplantation (preoperative thrombin activatable fibrinolysis inhibitor), immediately after the surgical procedure (immediate postoperative thrombin activatable fibrinolysis inhibitor), and 24 hours after surgery (thrombin activatable fibrinolysis inhibitor 24 hours after surgery). The primary outcome of the study was to correlate the preoperative and immediate postoperative levels of thrombin activatable fibrinolysis inhibitor with intraoperative blood loss.Results There was a correlation between the preoperative thrombin activatable fibrinolysis inhibitor levels and bleeding volume (ρ = -0.469; p = 0.05) but no correlation between the immediate postoperative thrombin activatable fibrinolysis inhibitor and bleeding volume (ρ = -0.062; p = 0.79). No variable included in the linear regression analysis (prehemoglobin, prefibrinogen and preoperative thrombin activatable fibrinolysis inhibitor) was a bleeding predictor. There was a similar trend in the variation between the levels of thrombin activatable fibrinolysis inhibitor at the three different time points and fibrinogen levels. Patients who died within 6 months (14.3%) showed decreased preoperative and immediate postoperative levels of thrombin activatable fibrinolysis compared with survivors (preoperative: 1.3 ± 0.15 versus 2.55 ± 0.53, p = 0.06; immediate postoperative: 1.2 ± 0.15 versus 2.5 ± 0.42, p = 0.007).Conclusion There was a moderate correlation between preoperative thrombin activatable fibrinolysis inhibitor and intraoperative bleeding in liver transplantation patients, although the predictive role of this variable independent of other variables remains uncertain. Preoperative and immediate postoperative thrombin activatable fibrinolysis inhibitor levels may have a role in the survival prognosis of this population; however, this possibility requires confirmation in further studies with larger sample sizes.