An international, multicenter, survey-based analysis of practice and management of acute liver failure.

Acute liver failure (ALF) is an acute liver dysfunction with coagulopathy and HE in a patient with no known liver disease. As ALF is rare and large clinical trials are lacking, the level of evidence regarding its management is low-moderate, favoring heterogeneous clinical practice. In this international multicenter survey study, we aimed to investigate the current practice and management of patients with ALF. An online survey targeting physicians who care for patients with ALF was developed by the International Liver Transplantation Society ALF Special-Interest Group. The survey focused on the management and liver transplantation (LT) practices of ALF. Survey questions were summarized overall and by geographic region. A total of 267 physicians completed the survey, with a survey response rate of 21.36%. Centers from all continents were represented. More than 90% of physicians specialized in either transplant hepatology/surgery or anesthesiology/critical care. Two hundred fifty-two (94.4%) respondents' institutions offered LT. A total of 76.8% of respondents' centers had a dedicated liver-intensive or transplant-intensive care unit ( p < 0.001). The median time to LT was within 48 hours in 12.7% of respondents' centers, 72 hours in 35.6%, 1 week in 37.6%, and more than 1 week in 9.6% ( p < 0.001). Deceased donor liver graft (49.6%) was the most common type of graft offered. For consideration of LT, 84.8% of physicians used King's College Criteria, and 41.6% used Clichy Criteria. Significant differences were observed between Asia, Europe, and North America for offering LT, number of LTs performed, volume of patients with ALF, admission to a dedicated intensive care unit, median time to LT, type of liver graft, monitoring HE and intracranial pressure, management of coagulopathy, and utilization of different criteria for LT. In our study, we observed significant geographic differences in the practice and management of ALF. As ALF is rare, multicenter studies are valuable for identifying global practice.

Bridging the critically ill patient with acute to chronic liver failure to liver transplantation.

Liver transplantation (LT) has emerged as an effective therapy for severe forms of acute-on-chronic liver failure (ACLF), an entity characterized by the development of multiorgan failure and high short-term mortality. The aim of critical care management of ACLF patients is to rapidly treat precipitating events and aggressively support failing organs to ensure that patients may successfully undergo LT or, less frequently, recover. Malnutrition and sarcopenia are frequently present, adversely impacting the prognosis of these patients. Management of critical care patients with ACLF is complex and requires the participation of different specialties. Once the patient is stabilized, a rapid evaluation for salvage LT should be performed because the time window for LT is often narrow. The development of sepsis and prolonged organ support may preclude LT or diminish its chances of success. The current review describes strategies to bridge severe ACLF patients to LT, highlights the minimal evaluation required for listing and the currently suggested contraindications to proceed with LT, and addresses different aspects of management during the perioperative and early posttransplant period.

Liver trauma in the intensive care unit.

PURPOSE OF REVIEW: To review the surgical and critical care management of liver trauma; one of the most common abdominal injuries sustained due to its size and location. RECENT FINDINGS: Hepatic injuries range from negligible to life threatening: in the acute phase, the most common cause of morbidity and mortality is hemorrhage; however, severe traumatic hepatic injuries can also lead to biochemical abnormalities, altered coagulation, and ultimately liver failure. This brief review will review the classification of traumatic liver injuries by mechanism, grade, and severity. Most Grades I-III injuries can be managed nonoperatively, whereas the majority of Grades IV-VI injuries require operative management. Therapeutic strategies for traumatic liver injury including nonoperative, operative, radiologic will be described. The primary goal of liver trauma management in the acute setting is hemorrhage control, then the management of secondary factors such as bile leaks. The rapid restoration of homeostasis may prevent further damage to the liver and allow for deferred nonoperative management, which has been shown to be associated with good clinical outcomes. SUMMARY: A multidisciplinary approach to the care of these patients at an experienced liver surgery center is warranted.

When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts.

BACKGROUND: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. METHODS: Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. RESULTS: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or <72 hours of appropriate antimicrobial therapy in case of ongoing sepsis were considered reasons to delay LT. A simple assessment of the number of organs failing was considered the most appropriate way to decide whether LT should be delayed or denied, with respiratory, circulatory and metabolic failures having the most influence in this decision. The thresholds of severity of organ failures contraindicating LT for which a consensus was achieved were a Pao2/FiO2 ratio<150 mm Hg, a norepinephrine dose >1 µg/kg per minute and a serum lactate level >9 mmol/L. CONCLUSIONS: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented.

Longterm Outcomes of Patients Undergoing Liver Transplantation for Acute-on-Chronic Liver Failure.

Recent data have demonstrated >80% 1-year survival probability after liver transplantation (LT) for patients with severe acute-on-chronic liver failure (ACLF). However, longterm outcomes and complications are still unknown for this population. Our aim was to compare longterm patient and graft survival among patients transplanted across all grades of ACLF. We analyzed the United Network for Organ Sharing database for the years 2004-2017. Patients with ACLF were identified using the European Association for the Study of the Liver-Chronic Liver Failure criteria. Kaplan-Meier and Cox regression methods were used to determine patient and graft survival and associated predictors of mortality in adjusted models. A total of 56,801 patients underwent transplantation of which 31,024 (54.6%) had no ACLF, 8757 (15.4%) had ACLF grade 1, 9039 (15.9%) had ACLF grade 2, and 7891 (14.1%) had ACLF grade 3. The 5-year patient survival after LT was lower in the ACLF grade 3 patients compared with the other groups (67.7%; P < 0.001), although after year 1, the percentage decrease in survival was similar among all groups. Infection was the primary cause of death among all patient groups in the first year. Infection was the primary cause of death among all patient groups in the first year. After the first year, infection was the main cause of death in patients transplanted with ACLF grade 1 (32.1%), ACLF grade 2 (33.9%), and ACLF grade 3 (37.6%), whereas malignancy was the predominant cause of death in those transplanted with no ACLF (28.5%). In conclusion, patients transplanted with ACLF grade 3 had lower 5-year survival as compared with patients with ACLF grades 0-2, but mortality rates were not significantly different after the first year following LT. Graft survival was excellent across all ACLF groups.

Significant lung injury and its prognostic significance in acute liver failure: A cohort analysis.

BACKGROUND AND AIMS: Respiratory failure complicating acute liver failure (ALF) may preclude liver transplantation (LT). We evaluated the association between significant lung injury (SLI) and important clinical outcomes. METHODS: Retrospective cohort study of 947 ALF patients with chest radiograph (CXR) and arterial blood gas (ABG) data enrolled in the US Acute Liver Failure Study Group (US-ALFSG) from January 1998 to December 2016. SLI was defined by moderate hypoxaemia (Berlin classification; PaO2 /FiO2  < 200 mm Hg) and abnormalities on CXR. Primary outcomes were 21-day transplant-free survival (TFS) and overall survival. RESULTS: Of 947 ALF patients, 370 (39%) had evidence of SLI. ALF patients with SLI (ALF-SLI) had significantly worse oxygenation than controls on admission (median PF ratio 120 vs 300 mm Hg, P < .0001) and higher lactate (6.1 vs 4.6 mmol/l, P = .0008). ALF-SLI patients had higher rates of tracheal (19% vs 14%) and bloodstream (17% vs 11%, P < .005 for both) infections and were more likely to receive transfusions (red cells 55% vs 43%; FFP 74% vs 66%; P < .009 for both). ALF-SLI patients were less likely to receive LT (18% vs 25%, P = .02) and had significantly decreased 21-day TFS (34% vs 42%) and overall survival (49% vs 64%, P < .007 for both). After adjusting for significant covariates (INR, bilirubin, acetaminophen aetiology), the development of SLI was independently associated with decreased 21-day TFS (OR 0.71, P = .03) in ALF patients (C-index 0.78). The incorporation of SLI improved discriminatory ability of the King's College Criteria (P = .0061) but not the ALFSG prognostic index (P = .34). CONCLUSION: Significant lung injury is a common complication in ALF patients that adversely affects patient outcomes.

The impact of cirrhosis in patients undergoing cardiac surgery: a retrospective observational cohort study.

PURPOSE: Patients with cirrhosis and concomitant coronary/valvular heart disease present a clinical dilemma. The therapeutic outcome of major cardiac surgery is significantly poorer in patients with cirrhosis compared with patients without cirrhosis. To address this, we aimed to identify associations between the severity of cirrhosis and post-cardiac surgical outcomes. METHODS: A historical cohort analysis of patients undergoing cardiac surgery at the University of Alberta Hospital from January 2004 to December 2014 was used to identify and propensity score-match 60 patients with cirrhosis to 310 patients without cirrhosis. The relationships between cirrhosis and i) mortality, ii) postoperative complications, and iii) requirement of healthcare resources were evaluated. RESULTS: Ten-year mortality was significantly higher in cirrhotic patients compared with propensity score-matched non-cirrhotic patients (40% vs 20%; relative risk [RR], 2.0; 95% confidence interval [CI], 1.3 to 2.9; P = 0.001). Cirrhotic patients had more complications (63% vs 48%; RR, 1.3; 95% CI, 1.05 to 1.7; P = 0.02), longer median [interquartile range (IQR)] intensive care unit stays (5 [3-11] vs 2 [1-4] days; P < 0.001), time on mechanical ventilation (median [IQR] 2 [1-5] vs 1 [0.5-1.2] days; P < 0.001) and more frequently required renal replacement therapy (15% vs 6%; RR, 2.5; 95% CI, 1.2 to 5.2; P = 0.02) postoperatively. After adjusting for other covariates, presence of cirrhosis (adjusted odds ratio, 2.2; 95% CI, 1.1 to 4.1) and intraoperative transfusion (adjusted odds ratio, 3.2; 95% CI, 1.6 to 6.3) were independently associated with increased mortality. CONCLUSION: Despite having low median model for end-stage liver disease scores, this small series of cirrhotic patients undergoing cardiac surgery had significantly higher mortality rates and required more organ support postoperatively than propensity score-matched non-cirrhotic patients. Impact de la cirrhose chez les patients subissant une chirurgie cardiaque : une étude de cohorte observationnelle et rétrospective.

The impact of delayed source control and antimicrobial therapy in 196 patients with cholecystitis-associated septic shock: a cohort analysis

Background: Cholecystitis-associated septic shock carries a significant mortality. Our aim was to determine whether timing of source control affects survival in cholecystitis patients with septic shock. Methods: We conducted a nested cohort study of all patients with cholecystitis-associated septic shock from an international, multicentre database (1996­2015). Multivariable logistic regression was performed to determine associations between clinical factors and in-hospital mortality. The results were used to inform a classification and regression tree (CART) analysis that modelled the association between disease severity (APACHE II), time to source control and survival. Results: Among 196 patients with cholecystitis-associated septic shock, overall mortality was 37%. Compared with nonsurvivors (n = 72), survivors (n = 124) had lower mean admission APACHE II scores (21 v. 27, p < 0.001) and lower median admission serum lactate (2.4 v. 6.8 µmol/L, p < 0.001). Survivors were more likely to receive appropriate antimicrobial therapy earlier (median 2.8 v. 6.1 h from shock, p = 0.012). Survivors were also more likely to undergo successful source control earlier (median 9.8 v. 24.7 h from shock, p < 0.001). Adjusting for covariates, APACHE II (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.06­1.21 per increment) and delayed source control > 16 h (OR 4.45, 95% CI 1.88­10.70) were independently associated with increased mortality (all p < 0.001). The CART analysis showed that patients with APACHE II scores of 15­26 benefitted most from source control within 16 h (p < 0.0001). Conclusion: In patients with cholecystitis-associated septic shock, admission APACHE II score and delay in source control (cholecystectomy or percutaneous cholecystostomy drainage) significantly affected hospital outcomes.

Contexte: Le choc septique associé à une cholécystite s'accompagne d'une mortalité significative. Notre but était de déterminer si le moment du contrôle de la source affecte la survie chez les patients atteints de cholécystite qui se trouvent en choc septique. Méthodes: Nous avons procédé à une étude de cohorte nichée regroupant tous les patients ayant présenté un choc septique associé à une cholécystite à partir d'une base de données multicentrique internationale (1996­2015). La régression logistique multivariée a été utilisée pour déterminer les liens entre les facteurs cliniques et la mortalité perhospitalière. Les résultats ont été utilisés pour éclairer une analyse par arbre de classification (CART) qui modélisait le lien entre la gravité de la maladie (APACHE II), le temps nécessaire au contrôle de la source et la survie. Résultats: Parmi 196 patients souffrant d'un choc septique associé à une cholécystite, la mortalité globale a été de 37 %. Comparativement aux patients décédés (n = 72), les survivants (n = 124) présentaient à l'admission des scores APACHE II moyens plus bas (21 c. 27, p < 0,001) et un taux de lactate sérique médian plus bas (2,4 c. 6,8 µmol/L, p < 0,001). Les survivants étaient plus susceptibles de recevoir une antibiothérapie adéquate plus hâtive (médiane 2,8 c. 6,1 h suivant le choc, p = 0,012). Les survivants étaient aussi plus susceptibles de bénéficier plus hâtivement d'un contrôle réussi de la source (médiane 9,8 c. 24,7 h suivant le choc, p < 0,001). L'ajustement pour tenir compte des covariables du score APACHE II (rapport des cotes [RC] 1,13, intervalle de confiance [IC] de 95 % 1,06­1,21 par palier) et le retard du contrôle de la source > 16 h (RC 4,45, IC de 95 % 1,88­10,70) ont été associés indépendamment à une mortalité plus élevée (tous deux p < 0,001). L'analyse CART a révélé que les patients ayant des scores APACHE II de 15­26 ont le plus bénéficié d'un contrôle de la source dans les 16 h (p < 0,0001). Conclusion: Chez les patients présentant un choc septique associé à une cholécystite, le score APACHE II à l'admission et le retard de contrôle de la source (cholécystectomie ou drainage par cholécystotomie percutanée) ont significativement influé sur les résultats hospitaliers.

Acute kidney injury in cirrhosis: implications for liver transplantation.

PURPOSE OF REVIEW: Acute kidney injury (AKI) in cirrhosis consists of varying phenotypes, with hepatorenal syndrome (HRS) representing a single entity. Prompt recognition and diagnosis of AKI cause identifies appropriate therapeutic measures. This review provides an overview of AKI definitions, highlights challenges in quantifying renal impairment in cirrhosis, lists novel diagnostic AKI biomarkers, and summarizes transplantation implications. RECENT FINDINGS: Biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18, and liver-type fatty acid-binding protein) may assist in the identification of underlying acute tubular necrosis. Of these, neutrophil gelatinase-associated lipocalin is the most promising; however, significant overlap occurs among AKI phenotypes, with diagnostic values yet to be defined. Mainstay treatment of HRS consists of albumin and vasopressors. Acute-on-chronic liver failure grade independently predicts response to terlipressin treatment. Many end-stage liver disease patients with AKI have underlying chronic kidney disease with important implications on pre and postliver transplantation mortality. Simultaneous liver-kidney transplant candidacy is based on low likelihood of renal recovery. SUMMARY: Novel biomarkers may assist in identification of acute tubular necrosis and persistent/severe AKI. Norepinephrine has been suggested to be inferior to terlipressin, with additional research required. Increasing acute-on-chronic liver failure grade correlates with lower likelihood of vasopressor response in HRS. Severe preliver transplantation AKI confers significantly worse postliver transplantation renal outcomes.

Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review.

BACKGROUND: Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. AIMS: To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. METHODS: The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. RESULTS: The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. CONCLUSIONS: Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.

Critical care management of the patient with cirrhosis awaiting liver transplant in the intensive care unit.

Patients with cirrhosis who are awaiting liver transplantation (LT) are at high risk for developing critical illnesses. Current liver allocation policies that dictate a "sickest first" approach coupled with a mismatch between need and availability of organs result in longer wait times, and thus, patients are becoming increasingly ill while awaiting organ transplantation. Even patients with well-compensated cirrhosis may suffer acute deterioration; the syndrome of acute-on-chronic liver failure (ACLF) results in multisystem organ dysfunction and a marked increase in associated short-term morbidity and mortality. For patients on transplant waiting lists, the development of multisystem organ failure may eliminate candidacy for transplant by virtue of being "too sick" to safely undergo transplantation surgery. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (eg, infection and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo LT. Management of the critically ill ACLF patient awaiting transplantation is best accomplished by multidisciplinary teams with expertise in critical care and transplant medicine. Such teams are well suited to address the needs of this unique patient population and to identify patients who may be too ill to proceed to transplantation surgery. The focus of this review is to identify the common complications of ACLF and to describe our approach management in critically ill patients awaiting LT in our centers. Liver Transplantation 23 1465-1476 2017 AASLD.

Clinical Impact of Portal Vein Thrombosis Prior to Liver Transplantation: A Retrospective Cohort Study

ABSTRACT Introduction. To identify the impact of portal vein thrombosis (PVT) and associated medical and surgical factors on outcomes post liver transplant (LT). Material and methods. Two analyses were performed. Analysis One: cohort study of 505 consecutive patients who underwent LT (Alberta) between 01/2002-12/2012. PVT was identified in 61 (14%) patients. Analysis Two: cohort study of 144 consecutive PVT patients from two sites (Alberta and London) during the same period. Cox multivariable survival analysis was used to identify independent associations with post-LT mortality. Results. In Analysis One (Alberta), PVT was not associated with post-LT mortality (log rank p = 0.99). On adjusted analysis, complete/occlusive PVT was associated with increased mortality (Hazard Ratio (HR) 8.4, p < 0.001). In Analysis Two (Alberta and London), complete/occlusive PVT was associated with increased mortality only on unadjusted analysis (HR 3.7, p = 0.02). On adjusted analysis, Hepatitis C (HR 2.1, p = 0.03) and post-LT portal vein re-occlusion (HR 3.2, p = 0.01) were independently associated with increased mortality. Conclusion: Well-selected LT patients who had PVT prior to LT had similar post-LT outcomes to non-PVT LT recipients. Subgroups of PVT patients who did worse post-LT (complete/occlusive thrombosis pre-LT, Hepatitis C or post-LT portal vein re-occlusion) warrant closer evaluation in listing and management post-LT.

HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death.

BACKGROUND & AIMS: Acute liver failure (ALF) caused by hepatitis B virus (HBV) infection can occur after immunosuppressive treatment and be fatal, although it might be preventable. We aimed to characterize the causes, clinical course, and short-term outcomes of HBV-associated ALF after immune-suppressive therapy, compared with patients with HBV-associated ALF without immunosuppression (control subjects). METHODS: We performed a retrospective multicenter study of 156 consecutive patients diagnosed with HBV-associated ALF (22 with a solid or blood malignancy) enrolled in the Acute Liver Failure Study Group registry from January 1998 through April 2015. We collected data on results of serologic and hepatic biochemistry analyses, grade of hepatic encephalopathy, Model for End-Stage Liver Disease score, and King's College criteria. We also collected data on clinical features, medical therapies, and complications in the first 7 days following study enrollment. Logistic regression was used to identify factors associated with transplant-free survival at 21 days in HBV-associated ALF (the primary outcome). RESULTS: Among patients with HBV-associated ALF, 28 cases (18%) occurred after immunosuppressive therapy (15 patients received systemic corticosteroids and 21 received chemotherapy); and 128 cases did not (control subjects, 82%). Significantly greater proportions of patients with HBV-associated ALF after immunosuppression were nonwhite persons, and had anemia or thrombocytopenia than controls (P < .02 for all). The serologic profile of HBV infection, severity of liver failure (based on MELD score), and complications (hepatic encephalopathy or need for mechanical ventilation, vasopressors, or renal replacement therapy) were similar between the groups (P > .17 for all). Factors associated with 21 day transplant-free survival were increased MELD score (odds ratio ∼OR, 0.894 (95% confidence interval 0.842-0.949 per increment), requirement for mechanical ventilation (OR 0.111(0.041-0.300), and immunosuppressive therapy (OR 0.274(0.082-0.923)). CONCLUSIONS: Within a cohort study of patients with HBV-associated ALF, 18% had received immunosuppressive therapy. Significantly smaller proportions of patients with HBV-associated ALF after immunosuppression survive beyond 21 days than patients with HBV-associated ALF who did not receive immunosuppression. Patients undergoing chemotherapy should be screened for HBV infection and given appropriate antiviral therapies to reduce preventable mortality.

Acute liver injury and acute liver failure from mushroom poisoning in North America.

BACKGROUND & AIMS: Published estimates of survival associated with mushroom (amatoxin)-induced acute liver failure (ALF) and injury (ALI) with and without liver transplant (LT) are highly variable. We aimed to determine the 21-day survival associated with amatoxin-induced ALI (A-ALI) and ALF (A-ALF) and review use of targeted therapies. METHODS: Cohort study of all A-ALI/A-ALF patients enrolled in the US ALFSG registry between 01/1998 and 12/2014. RESULTS: Of the 2224 subjects in the registry, 18 (0.8%) had A-ALF (n = 13) or A-ALI (n = 5). At admission, ALF patients had higher lactate levels (5.2 vs. 2.2 mm, P = 0.06) compared to ALI patients, but INR (2.8 vs. 2.2), bilirubin (87 vs. 26 µm) and MELD scores (28 vs. 24) were similar (P > 0.2 for all). Of the 13 patients with ALF, six survived without LT (46%), five survived with LT (39%) and two died without LT (15%). Of the five patients with ALI, four (80%) recovered and one (20%) survived post-LT. Comparing those who died/received LT (non-spontaneous survivors [NSS]) with spontaneous survivors (SS), N-acetylcysteine was used in nearly all patients (NSS 88% vs. SS 80%); whereas, silibinin (25% vs. 50%), penicillin (50% vs. 25%) and nasobiliary drainage (0 vs. 10%) were used less frequently (P > 0.15 for all therapies). CONCLUSION: Patients with mushroom poisoning with ALI have favourable survival, while around half of those presenting with ALF may eventually require LT. Further study is needed to define optimal management (including the use of targeted therapies) to improve survival, particularly in the absence of LT.

Detection of Ophthalmic Acid in Serum from Acetaminophen-Induced Acute Liver Failure Patients Is More Frequent in Non-Survivors.

BACKGROUND/AIM: Acetaminophen (APAP) hepatotoxicity is related to the formation of N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified through conjugation with reduced glutathione (GSH). Ophthalmic acid (OA) is an analogue of GSH in which cysteine is replaced with 2-aminobutyrate. Metabolomics studies of mice with APAP-induced acute liver failure (APAP-ALF) identified OA as a marker of oxidative stress and hepatic GSH consumption. The aim of the current study was to determine whether OA is detectable in APAP-ALF human patients either early (day 2) or late (day 4) and whether OA levels were associated with in-hospital survival in the absence of liver transplant. METHODS: Serum samples from 130 APAP-ALF patients (82 survivors, 48 non-survivors) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and correlated with clinical data from the United States Acute Liver Failure Study Group (US ALFSG) Registry (2004-2011). RESULTS: Survivors had significantly lower admission bilirubin (4.2 vs. 5.7 mg/dl) and lactate levels (3.3 vs. 6.5 µmol/l, p<0.05 for all). During the first 7 days of the study, survivors were less likely to require mechanical ventilation (55% vs. 88%), vasopressor support (9.8% vs. 67%) or renal replacement therapy (26% vs. 63%, p< 0.001 for all). Non-survivors were more likely to have detectable OA levels early (31% vs. 15%, p = 0.034) and late (27% vs. 11%, p = 0.02). However there were no significant differences in mean OA levels between non-survivors and survivors (early 0.48 vs. 0.36, late 0.43 vs. 0.37, P > 0.5 for all). CONCLUSION: OA was detectable more frequently in APAP-ALF non-survivors but mean OA levels were not associated with survival. The routine clinical administration of N-acetyl cysteine could replenish GSH levels and prevent OA production.

Acute Kidney Injury in Cirrhosis.

Acute kidney injury (AKI) is a frequent complication of end-stage liver disease, especially in those with acute-on-chronic liver failure, occurring in up to 50% of hospitalized patients with cirrhosis. There is no specific blood or urine biomarker that can reliably identify the cause of AKI in cirrhotic patients. This review examines studies used to assess renal dysfunction in cirrhotic patients including new diagnostic criteria and potential novel biomarkers. Although biomarker development to differentiate the cause of AKI in cirrhosis has promise, the utility of biomarkers to determine irreversible renal dysfunction with liver transplant remains lacking, warranting further investigation.

Postoperative resource utilization and survival among liver transplant recipients with Model for End-stage Liver Disease score ≥ 40: A retrospective cohort study.

BACKGROUND: Cirrhotic patients with Model for End-stage Liver Disease (MELD) score ≥ 40 have high risk for death without liver transplant (LT). OBJECTIVE: To evaluate these patients' outcomes after LT. METHODS: The present study analyzed a retrospective cohort of 519 cirrhotic adult patients who underwent LT at a single Canadian centre between 2002 and 2012. Primary exposure was severity of liver disease measured by MELD score at LT (≥ 40 versus < 40). Primary outcome was duration of first intensive care unit (ICU) stay after LT. Secondary outcomes were duration of first hospital stay after LT, rate of ICU readmission, re-LT and survival rates. RESULTS: On the day of LT, 5% (28 of 519) of patients had a MELD score ≥ 40. These patients had longer first ICU stays after LT (14 versus two days; P < 0.001). MELD score ≥ 40 at LT was independently associated with first ICU stay after LT ≥ 10 days (OR 3.21). These patients had longer first hospital stays after LT (45 versus 18 days; P < 0.001); however, there was no significant difference in the rate of ICU readmission (18% versus 22%; P = 0.58) or re-LT rate (4% versus 4%; P = 1.00). Cumulative survival at one month, three months, one year, three years and five years was 98%, 96%, 90%, 79% and 72%, respectively. There was no significant difference in cumulative survival stratified according to MELD score ≥ 40 versus < 40 at LT (P = 0.59). CONCLUSIONS: Cirrhotic patients with MELD score ≥ 40 at LT utilize greater postoperative health resources; however, they derive similar long-term survival benefit from LT.

Increased health services use by severely obese patients undergoing emergency surgery: a retrospective cohort study.

BACKGROUND: The aim of this study was to assess perioperative outcomes in obese patients undergoing emergency surgery. METHODS: We retrospectively reviewed the charts of all adult (> 17 yr) patients admitted to the acute care emergency surgery service at the University of Alberta Hospital between January 2009 and December 2011 who had a body mass index (BMI) of 35 or higher. Patients were divided into subgroups for analysis based on "severe" (BMI 35-39.9) and "morbid" obesity (BMI ≥ 40). Multivariate logistic regression was performed to identify predictors of in-hospital mortality after controlling for confounding factors. RESULTS: Data on 111 patients (55% women, median BMI 39) were included in the final analysis. Intensive care unit (ICU) support was required for 40% of patients. Postoperative complications occurred in 42% of patients, and 31% required reoperation. Overall in-hospital mortality was 17%. Morbidly obese patients had increased rates of reoperation (40% v. 23%, p = 0.05) and increased lengths of stay compared with severely obese patients (14.5 v. 6.0 d, p = 0.09). Age (odds ratio [OR] 1.08 per increment) and preoperative ICU stay (OR 12) were significantly associated with in-hospital mortality after controlling for confounding, but BMI was not. CONCLUSION: Obese patients requiring emergency surgery represent a complex patient population at high risk for perioperative morbidity and mortality. Greater resources are required for their care, including ICU support, repeat surgery and prolonged ICU stay. Future studies could help identify predictors of reoperation and strategies to optimize nutrition, rehabilitation and resource allocation.

CONTEXTE: Cette étude avait pour objet d'évaluer les résultats périopératoires chez des patients obèses soumis à une chirurgie d'urgence. MÉTHODES: Nous avons passé en revue de manière rétrospective les dossiers de tous les patients adultes (> 17 ans) pris en charge par l'équipe de chirurgie d'urgence du Centre hospitalier de l'Université de l'Alberta entre janvier 2009 et décembre 2011 et dont l'indice de masse corporelle (IMC) était de 35 ou plus. Aux fins de l'analyse, les patients ont été répartis en 2 groupes selon qu'ils présentaient une obésité « grave ¼ (IMC 35­39,9) ou « morbide ¼ (IMC ≥ 40). Nous avons utilisé un modèle d'analyse de régression logistique multivariée pour reconnaître les prédicteurs de la mortalité perhospitalière après avoir tenu compte des facteurs de confusion. RÉSULTANTS: L'analyse finale a porté sur les données concernant 111 patients (55 % de femmes, IMC médian 39). Il a fallu faire appel à l'Unité des soins intensifs (USI) pour 40 % des patients. Des complications postopératoires sont survenues chez 42 % des patients et 31 % ont nécessité une réopération. Dans l'ensemble, la mortalité perhospitalière a été de 17 %. Les patients atteints d'obésité morbide ont présenté des taux plus élevés de réopération (40 % c. 23 %, p = 0,05) et des séjours hospitaliers plus longs comparativement aux patients souffrant d'obésité grave (14,5 c. 6,0 jours, p = 0,09). L'âge (rapport des cotes [RC] 1,08 par palier) et un séjour préopératoire à l'USI (RC 12) ont été significativement associés à la mortalité perhospitalière après contrôle des facteurs de confusion, mais non l'IMC. CONCLUSION: Les patients obèses qui ont besoin d'une chirurgie urgente forment une population de patients complexe exposée à un risque élevé de morbidité et de mortalité périopératoires. Leurs soins requièrent plus de ressources, y compris recours à l'USI, reprise de la chirurgie et prolongation du séjour à l'USI. D'autres études pourraient aider à recenser les prédicteurs des réopérations et à trouver des stratégies d'optimisation de la nutrition, de la réadaptation et de l'attribution des ressources.

Sarcopenia is a predictor of outcomes in very elderly patients undergoing emergency surgery.

BACKGROUND: With the increasing aging population, the number of very elderly patients (age ≥80 years) undergoing emergency operations is increasing. Evaluating patient-specific risk factors for postoperative morbidity and mortality in the acute care surgery setting is crucial to improving outcomes. We hypothesize that sarcopenia, a severe depletion of skeletal muscles, is a predictor of morbidity and mortality in very elderly patients undergoing emergency surgery. METHODS: A total of 170 patients older than the age of 80 underwent emergency surgery between 2008 and 2010 at a tertiary care facility; 100 of these patients had abdominal computed tomography images within 30 days of the operation that were adequate for the assessment of sarcopenia. The impact of sarcopenia on the operative outcomes was evaluated using both univariate and multivariate analysis. RESULTS: The mean patient age was 84 years, with an in-hospital mortality of 18%. Sarcopenia was present in 73% of patients. More sarcopenic patients had postoperative complications (45% sarcopenic versus 15% nonsarcopenic, P = .005) and more died in hospital (23 vs 4%, P = .037). There were no differences in duration of stay or requirement for intensive care unit postoperatively. After we controlled for confounding factors, increasing skeletal muscle index (per incremental cm(2)/m(2)) was associated with decreased in-hospital mortality (odds ratio ∼0.834, 95% confidence interval 0.731-0.952, P = .007) in multivariate analysis. CONCLUSION: Sarcopenia was independently predictive of greater complication rates, discharge disposition, and in-hospital mortality in the very elderly emergency surgery population. Using sarcopenia as an objective tool to identify high-risk patients would be beneficial in developing tailored preventative strategies and potentially resource allocation in the future.