Long-term outcome following liver transplantation of patients with ACLF grade 3.

BACKGROUND AND AIMS: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included the three-center retrospective French experience published in 2017. METHOD: All patients with ACLF-3 (n=73) as well as their transplanted matched controlled with ACLF-2 (n=145), 1 (n=119) and no ACLF (n=292) that have participated in the princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survivals, causes of death and their predictive factors. RESULTS: Median follow-up of patients ACLF-3 patients was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patients' survivals were respectively 72.6% vs. 69.7% vs. 76.4% vs. 77.0% (p=0.31). Ten-year patients' survival ACLF-3 was 56.8% and was not different other groups (p=0.37) Leading causes of death in ACLF-3 patients were infections (33.3%), and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and Chronic Liver Failure Consortium ACLF score were independently associated with 10-year patients' survival. Long-term grafts' survivals were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years. CONCLUSION: 5- and 10-year patients' and grafts' survivals in ACLF-3 patients were not different from their controls. 5-year patients' survival is higher than that of the 50%-70% threshold defining the utility of liver graft. Efforts should focus on candidates' selection based on comorbidities as well as the prevention of infection and cardiovascular events standing as the main cause of death. IMPACT AND IMPLICATIONS: While short-term outcomes following liver transplantation in the most severely ill cirrhotic patients (ACLF-3) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favorable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in ACLF-3 patients compared to matched ACLF-2, ACLF-1, and no-ACLF patients. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidities evaluation, such as the age-adjusted Charlson Comorbidity Index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and managing tightly cardiovascular risk over time.

Tumors located in the central column of the liver are associated with increased surgical difficulty and postoperative complications following open liver resection for colorectal metastases.

BACKGROUND: To assess the impact of difficult location (based on preoperative computed tomography) of liver metastases from colorectal cancer (LMCRC) on surgical difficulty, and occurrence of severe postoperative complications (POCs). METHODS: A retrospective single-centre study of 911 consecutive patients with LMCRC who underwent hepatectomy by the open approach between 1998 and 2011, before implementation of laparoscopic surgery to obviate approach selection bias. LMCRC with at least one of the following four features on preoperative imaging: tumor invading the hepatocaval confluence or retro-hepatic inferior vena cava, centrally located (Segments 4,5,8) and >10 cm in diameter, abutting the supra-hilar area, or involving the paracaval portion or caudate process of Segment 1; were considered as topographically difficult (top-diff). Independent predictors of surgical difficulty assessed by number of blood units transfused, duration of ischemia, and number of sessions of pedicle clamping during surgery and of severe POCs were identified by multivariate analysis before, and after propensity score matching. RESULTS: Top-diff tumor location independently predicted surgical difficulty. Severe POCs were associated with the tumor location [top-diff vs. topographically non difficult (non top-diff)], preoperative portal vein embolization, and variables related to surgical difficulty. CONCLUSION: LMCRC in difficult location independently predicts surgical difficulty and severe POCs.

Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score.

BACKGROUND & AIMS: In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. METHODS: This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 µmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3-D0)/D0. RESULTS: A total of 128 patients were included, with a median age of 52 (39-62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23-21.06; p <0.001), Δ%3-INR ≥0.1% (OR 6.97; 95% CI 1.59-30.46; p <0.01) and Δ%3-bilirubin ≥-8% (OR 5.14; 95% CI 1.09-24.28; p <0.04) were predictive of a non-response. The SURFASA score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (AUC = 0.93) (88% specificity; 84% sensitivity) with a cut-off point of <-0.9. Below this cut-off, the chance of responding was 75%. With a score higher than 1.75, the risk of dying or being transplanted was between 85% and 100%. CONCLUSION: In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. LAY SUMMARY: The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.

Mild increases in plasma creatinine after intermediate to high-risk abdominal surgery are associated with long-term renal injury.

BACKGROUND: The potential relationship between a mild acute kidney injury (AKI) observed in the immediate postoperative period after major surgery and its effect on long term renal function remains poorly defined. According to the "Kidney Disease: Improving Global Outcomes" (KDIGO) classification, a mild injury corresponds to a KIDIGO stage 1, characterized by an increase in creatinine of at least 0.3 mg/dl within a 48-h window or 1.5 to 1.9 times the baseline level within the first week post-surgery. We tested the hypothesis that patients who underwent intermediate-to high-risk abdominal surgery and developed mild AKI in the following days would be at an increased risk of long-term renal injury compared to patients with no postoperative AKI. METHODS: All consecutive adult patients with a plasma creatinine value ≤1.5 mg/dl who underwent intermediate-to high-risk abdominal surgery between 2014 and 2019 and who had at least three recorded creatinine measurements (before surgery, during the first seven postoperative days, and at long-term follow up [6 months-2 years]) were included. AKI was defined using a "modified" (without urine output criteria) KDIGO classification as mild (stage 1 characterised by an increase in creatinine of > 0.3 mg/dl within 48-h or 1.5-1.9 times baseline) or moderate-to-severe (stage 2-3 characterised by increase in creatinine 2 to 3 times baseline or to ≥4.0 mg/dl). The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the same KDIGO initiative criteria. Development of long-term renal injury was compared in patients with and without postoperative AKI. RESULTS: Among the 815 patients included, 109 (13%) had postoperative AKI (81 mild and 28 moderate-to-severe). The median long-term follow-up was 360, 354 and 353 days for the three groups respectively (P = 0.2). Patients who developed mild AKI had a higher risk of long-term renal injury than those who did not (odds ratio 3.1 [95%CI 1.7-5.5]; p < 0.001). In multivariable analysis, mild postoperative AKI was independently associated with an increased risk of developing long-term renal injury (adjusted odds ratio 4.5 [95%CI 1.8-11.4]; p = 0.002). CONCLUSIONS: Mild AKI after intermediate-to high-risk abdominal surgery is associated with a higher risk of long-term renal injury 1 y after surgery.

Mass Spectrometry-Based Proteomics Reveal Alcohol Dehydrogenase 1B as a Blood Biomarker Candidate to Monitor Acetaminophen-Induced Liver Injury.

Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10-48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI.

Liver transplantation in patients with liver failure related to exertional heatstroke.

BACKGROUND & AIMS: Severe acute liver injury is a grave complication of exertional heatstroke. Liver transplantation (LT) may be a therapeutic option, but the criteria for LT and the optimal timing of LT have not been clearly established. The aim of this study was to define the profile of patients who require transplantation in this context. METHODS: This was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related severe acute liver injury with a prothrombin time (PT) of less than 50%. A total of 24 male patients were studied. RESULTS: Fifteen of the 24 patients (median nadir PT: 35% [29.5-40.5]) improved under medical therapy alone and survived. Nine of the 24 were listed for emergency LT. At the time of registration, the median PT was 10% (5-12) and all had numerous dysfunctional organs. Five patients (nadir PT: 12% [9-12]) were withdrawn from the list because of an elevation of PT values that mainly occurred between day 2 and day 3. Ultimately, 4 patients underwent transplantation as their PT persisted at <10%, 3 days (2.75-3.25) after the onset of exertional heatstroke, and they had more than 3 organ dysfunctions. Of these 4 patients, 3 were still alive 1 year later. Histological analysis of the 4 explanted livers demonstrated massive or sub-massive necrosis, and little potential for effective mitoses, characterised by a "mitonecrotic" appearance. CONCLUSION: The first-line treatment for exertional heatstroke-related severe acute liver injury is medical therapy. LT is only a rare alternative and such a decision should not be taken too hastily. A persistence of PT <10%, without any signs of elevation after a median period of 3  days following the onset of heatstroke, was the trigger that prompted LT, was the trigger adopted in order to decide upon LT. LAY SUMMARY: Acute liver injury due to heatstroke can progress to acute liver failure with organ dysfunction despite medical treatment; in such situations, liver transplantation (LT) may offer a therapeutic option. The classic criteria for LT appear to be poorly adapted to heatstroke-related acute liver failure. We confirmed thatmedication is the first-line therapy acute liver injury caused by heatstroke, with LT only rarely necessary. A decision to perform LT should not be made hastily. Fluctuations in prothrombin time and the patient's clinical status should be considered even in the event of severe liver failure.

Arterial Lactate Concentration at the End of Liver Transplantation Is an Early Predictor of Primary Graft Dysfunction.

BACKGROUND: Although many prognostic factors of primary graft dysfunction after liver transplantation (LT) are available, it remains difficult to predict failure in a given recipient. OBJECTIVE: We aimed to determine whether the intraoperative assay of arterial lactate concentration at the end of LT (LCEOT) might constitute a reliable biological test to predict early outcomes [primary nonfunction (PNF), early graft dysfunction (EAD)]. METHODS: We reviewed data from a prospective database in a single center concerning patients transplanted between January 2015 and December 2016 (n = 296). RESULTS: There was no statistical imbalance between the training (year 2015) and validation groups (year 2016) for epidemiological and perioperative feature. Ten patients (3.4%) presented with PNF, and EAD occurred in 62 patients (20.9%); 9 patients died before postoperative day (POD) 90. LCEOT ≥5 mmol/L was the best cut-off point to predict PNF (Se=83.3%, SP=74.3%, positive likelihood ratio (LR+)=3.65, negative likelihood ratio (LR-)=0.25, diagnostic odds ratio (DOR)=14.44) and was predictive of PNF (P = 0.02), EAD (P = 0.05), and death ≤ POD90 (P = 0.06). Added to the validated BAR-score, LCEOT improved its predictive value regarding POD 90 survival with a better AUC (0.87) than BAR score (0.74). The predictive value of LCEOT was confirmed in the validation cohort. CONCLUSION: As a reflection of both hypoperfusion and tissue damage, the assay of arterial LCEOT ≥5 mmol/L appears to be a strong predictor of early graft outcomes and may be used as an endpoint in studies assessing the impact of perioperative management. Its accessibility and low cost could impose it as a reliable parameter to anticipate postoperative management and help clinicians for decision-making in the first PODs.

Long-lasting successful dissemination of resistance to oxazolidinones in MDR Staphylococcus epidermidis clinical isolates in a tertiary care hospital in France.

OBJECTIVES: Patient- and procedure-related changes in modern medicine have turned CoNS into one of the major nosocomial pathogens. Treatments of CoNS infections are challenging owing to the large proportion of MDR strains and oxazolidinones often remain the last active antimicrobial molecules. Here, we have investigated a long-lasting outbreak (2010-13) due to methicillin- and linezolid-resistant (LR) CoNS (n = 168), involving 72 carriers and 49 infected patients. METHODS: Antimicrobial susceptibilities were tested by the disc diffusion method and MICs were determined by broth microdilution or Etest. The clonal relationship of LR Staphylococcus epidermidis (LRSE) was first determined using a semi-automated repetitive element palindromic PCR (rep-PCR) method. Then, WGS was performed on all cfr-positive LRSE (n = 30) and LRSE isolates representative of each rep-PCR-defined clone (n = 17). Self-transferability of cfr-carrying plasmids was analysed by filter-mating experiments. RESULTS: This outbreak was caused by the dissemination of three clones (ST2, ST5 and ST22) of LRSE. In these clones, linezolid resistance was caused by (i) mutations in the chromosome-located genes encoding the 23S RNA and L3 and L4 ribosomal proteins, but also by (ii) the dissemination of two different self-conjugative plasmids carrying the cfr gene encoding a 23S RNA methylase. By monitoring linezolid prescriptions in two neighbouring hospitals, we highlighted that the spread of LR-CoNS was strongly associated with linezolid use. CONCLUSIONS: Physicians should be aware that plasmid-encoded linezolid resistance has started to disseminate among CoNS and that rational use of oxazolidinones is critical to preserve these molecules as efficient treatment options for MDR Gram-positive pathogens.

Liver transplantation in the most severely ill cirrhotic patients: A multicenter study in acute-on-chronic liver failure grade 3.

BACKGROUND & AIMS: Liver transplantation (LT) for the most severely ill patients with cirrhosis, with multiple organ dysfunction (accurately assessed by the acute-on-chronic liver failure [ACLF] classification) remains controversial. We aimed to report the results of LT in patients with ACLF grade 3 and to compare these patients to non-transplanted patients with cirrhosis and multiple organ dysfunction as well as to patients transplanted with lower ACLF grade. METHODS: All patients with ACLF-3 transplanted in three liver intensive care units (ICUs) were retrospectively included. Each patient with ACLF-3 was matched to a) non-transplanted patients hospitalized in the ICU with multiple organ dysfunction, or b) control patients transplanted with each of the lower ACLF grades (three groups). RESULTS: Seventy-three patients were included. These severely ill patients were transplanted following management to stabilize their condition with a median of nine days after admission (progression of mean organ failure from 4.03 to 3.67, p=0.009). One-year survival of transplanted patients with ACLF-3 was higher than that of non-transplanted controls: 83.9 vs. 7.9%, p<0.0001. This high survival rate was not different from that of matched control patients with no ACLF (90%), ACLF-1 (82.3%) or ACLF-2 (86.2%). However, a higher rate of complications was observed (100 vs. 51.2 vs. 76.5 vs. 74.3%, respectively), with a longer hospital stay. The notion of a "transplantation window" is discussed. CONCLUSIONS: LT strongly influences the survival of patients with cirrhosis and ACLF-3 with a 1-year survival similar to that of patients with a lower grade of ACLF. A rapid decision-making process is needed because of the short "transplantation window" suggesting that patients with ACLF-3 should be rapidly referred to a specific liver ICU. Lay summary: Liver transplantation improves survival of patients with very severe cirrhosis. These patients must be carefully monitored and managed in a specialized unit. The decision to transplant a patient must be quick to avoid a high risk of mortality.

The impact of expanded indications on short-term outcomes for resection of malignant tumours of the liver over a 30 year period.

BACKGROUND: There are two philosophical approaches to planning liver resection for malignancy: one strives towards zero postoperative mortality by stringent selection of candidates, thus inherently limiting patients selected; the other, accepts a low yet definite postoperative mortality rate, and offers surgery to all those with potential gain in survival. The aim of this study was to retrospectively analyse an alternative and evolving strategy, and its impact on short-term outcomes. METHOD: 3118 consecutive hepatectomies performed in 2627 patients over 3 decades (1980-2011) were analysed. Patient demographics, tumour characteristics, operative details, and postoperative outcomes were analysed. RESULTS: 1528 patients (58%) were male. Colorectal liver metastases (1221 patients, 47%) and hepatocellular carcinoma (584 patients, 22%) were the most common diagnoses. Anatomical resections were performed in 2045 (66%), some form of vascular clamping was used in 2385 (72%), and blood transfusion was required in 1130 (36%) patients. Use of preoperative techniques to increase feasibility and safety of complex liver resections allowed expansion of indications to include sicker patients with larger tumours in the later period of the study. Overall morbidity and mortality rates were 31% and 3% respectively. During the first vs. second half of the study period the postoperative morbidity and mortality were 19% vs. 36% (p < 0.001) and 2% vs. 4% (p = 0.006) respectively. CONCLUSION: With increasing experience, more patients were accepted for complex hepatectomies. However, there was a definite yet contained increase in postoperative morbidity and mortality.

Repeat liver retransplantation: rationale and outcomes.

BACKGROUND: Liver retransplantation remains the only option for recurrent graft failure. The aim of our study is to identify predictive factors involved in patients and graft survival for patients undergoing repeat retransplantation (RRT). METHODOLOGY: From January 1985 to December 2012, 2940 liver transplantations were performed in 2477 patients at Paul Brousse Hospital, Villejuif, France. All patients who underwent third, fourth, and fifth transplantation were included in the study and retrospectively analyzed. RESULTS: In the univariate analysis, the factors that were associated with 90-d patient post-operative survival were pre-operative vasopressors support, pre-operative extra hepatic sepsis, primary non-function (PNF) as indication of RRT, recipient's model of end stage liver disease (MELD), urgent RRT, creatinine value at RRT, and prothrombin ratio. The multivariate logistic regression confirmed the role of systemic septic status (OR = 12.8, p = 0.01) and vasopressor drug support (OR = 4.7, p = 0.05) as predictors of post-operative mortality. In the univariate analysis, the factors that were associated with patient 10 yr long-term survival (were vasopressor support, systemic septic patient, PNF as indication of RRT, RRT occurred between 1985 and 1999, recipient's MELD, creatinine value at RRT, and prothrombin ratio. The multivariate logistic regression confirmed the role of systemic septic patient (OR = 6.4, p = 0.03) and the RRT between 1985 and 1999 (OR = 3.6, p = 0.05) as predictors of long-term mortality. CONCLUSION: RRT represent a valid alternative in selected patients. Selection should be oriented on patients needing third transplant without extra hepatic sepsis and vasoactive drug support at moment of RRT. If necessary, fourth and fifth RRT could be performed with a decision made on case-by-case basis, despite a high post-operative mortality.

Central Hepatectomy versus Extended Hepatectomy for Malignant Tumors: A Propensity Score Analysis of Postoperative Complications.

BACKGROUND: The specific definition of central hepatectomy (CH) (i.e., resection of segments 4-5-8 ± 1) is not uniformly used, resulting in conflicting comparisons with the more commonly performed extended hepatectomy (EH). The study aimed to compare, using propensity score matching (PSM) analysis, the incidence of postoperative complications between CH and EH for centrally located liver tumors (CLLT). METHODS: All consecutive CH and EH procedures for CLLT performed from 1980 to 2011 were retrospectively reviewed. Independent predictors of postoperative complications were identified. CH was compared to EH after PSM. RESULTS: The study population consisted of 373 patients, 44 (11.8 %) of whom underwent CH and 329 (88.2 %) of whom underwent EH. Before PSM, the overall 90-day mortality was 7.2 % (27 patients) without a group difference (2 (4.5 %) for CH vs. 25 (7.6 %) for EH, p = 0.756). The CH and EH groups had similar postoperative morbidity rates (43.2 vs. 55.3 %; p = 0.108). Blood transfusion was the only independent predictor of postoperative complications (Hazard Ratio: 1.73; 95 % confidence interval: 1.11-2.68; p = 0.014). After PSM, 43 CH patients were matched with 43 EH patients. No group difference was observed for the postoperative mortality, morbidity, or duration of hospital stay. A higher number of EH patients (30.2 vs. 9.3 %, p = 0.028) presented with more than one postoperative complication. CONCLUSIONS: CH and EH yield similar mortality and morbidity. For CLLT, CH may be an attractive procedure with the advantage of sparing the liver parenchyma compared with EH.

Patients with acute liver failure listed for superurgent liver transplantation in France: reevaluation of the Clichy-Villejuif criteria.

In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non-paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance≥60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level<200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level>20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level<200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non-paracetamol-induced ALF were split and 2 other items were included in this model: the bilirubin level and creatinine clearance.

Hepatitis E infection in patients with severe acute alcoholic hepatitis.

BACKGROUND & AIMS: Hepatitis E virus (HEV) infection is a known cause of acute-on-chronic liver failure in developing countries, but its implication in Western countries remains unknown. HEV burden in the setting of severe acute alcoholic hepatitis (AAH) was assessed. METHODS: Patients admitted for severe AAH from 2007 to 2013, with available sera and histologically proven AAH, were included and managed according to current European guidelines. At admission, clinical and biological characteristics were collected; HEV serology and RNA detection were retrospectively performed. RESULTS: Eighty-four patients were included. Mean age was 50.8 ± 9.6 years, 65.5% were male, 91.7% were cirrhotic and 33.3% presented with encephalopathy. Mean MELD and Maddrey scores were respectively 32.4 ± 11.4 and 73.3 ± 37. Liver biopsy showed mild, moderate and severe hepatitis in 25 (29.8%), 23 (27.4%) and 32 (38.1%) patients respectively. Steroids were given to 61 patients (72.6%) of whom 35 (57.4%) presented corticoresistance (mean Lille score: 0.78 ± 0.21). During hospitalization, 24 patients (28.6%) died and 11 (13.1%) were transplanted. Three patients (3.6%) presented markers of acute HEV infection and 21 (25%) markers of past HEV infection. Patient with acute infection were men, cirrhotic, and 2/3 presented with encephalopathy. Steroids were given to two patients without any response. The third patient died. None were transplanted. CONCLUSIONS: A substantial proportion of patients with severe AAH had markers of acute HEV infection, with similar clinical presentation and outcomes. Larger studies are needed to evaluate HEV impact on AAH management, resistance to steroids, and outcome.

The implementation of an Intensive Care Information System allows shortening the ICU length of stay.

Intensive care information systems (ICIS) implemented in intensive care unit (ICU) were shown to improve patient safety, reduce medical errors and increase the time devolved by medical/nursing staff to patients care. Data on the real impact of ICIS on patient outcome are scarce. This study aimed to evaluate the effects of ICIS on the outcome of critically-ill patients. From January 2004 to August 2006, 1,397 patients admitted to our ICU were enrolled in this observational study. This period was divided in two phases: before the implementation of ICIS (BEFORE) and after implementation of ICIS (AFTER). We compared standard ICU patient's outcomes: mortality, length of stay in ICU, hospital stay, and the re-admission rate depending upon BEFORE and AFTER. Although patients admitted AFTER were more severely ill than those of BEFORE (SAPS II: 32.1±17.5 vs. 30.5±18.5, p=0.014, respectively), their ICU length of stay was significantly shorter (8.4±15.2 vs. 6.8±12.9 days; p=0.048) while the re-admission rate and mortality rate were similar (4.4 vs. 4.2%; p=0.86, and 9.6 vs 11.2% p=0.35, respectively) in patients admitted AFTER. We observed that the implementation of ICIS allowed shortening of ICU length of stay without altering other patient outcomes.

Outcome of patients with cirrhosis requiring mechanical ventilation in ICU.

INTRODUCTION: Mortality rate of patients with cirrhosis admitted to the intensive care unit (ICU) and requiring mechanical ventilation varies between 60 and 91%. The aim of our study is to assess the prognosis of these patients, their 1-year outcome and to analyze predictive factors of long-term mortality. METHODS: From May 2005 to May 2011, we studied 246 consecutive patients with cirrhosis requiring mechanical ventilation either at admission or during their ICU stay. RESULTS: Alcohol was the most common etiology of the cirrhosis (69%). Bleeding related to portal hypertension (30%) and severe sepsis (33%) were the most common reasons for admission. ICU and hospital mortality were respectively 65.9% and 70.3%. Prognostic severity scores, the need for other organ support therapy, infection, and total bilirubin value at ICU admission were significantly associated with ICU mortality. Eighty-four patients (34.1%) were discharged from the ICU. Among these patients, the one-year survival was only of 32%. Logistic regression analysis, using survival at one year as the endpoint, identified two independent risk factors: the length of ventilation (odds ratio [OR] = 1.1; 95% CI, 1.0-1.2; p = 0.02) and total bilirubin at ICU discharge (OR = 1.3; 95% CI, 1.1-1.5; p = 0.006). CONCLUSION: Patients with cirrhosis admitted to the liver ICU and who required mechanical ventilation have a poor prognosis with a 1-year mortality of 89%. At ICU discharge, a total bilirubin level higher than 64.5 µmol/L and length of ventilation higher than 9 days could help the hepatologists to identify patients at risk of death in the year following the ICU discharge.

Long term results of liver transplantation for Wilson's disease: experience in France.

BACKGROUND & AIMS: Liver transplantation (LT) is the therapeutic option for severe complications of Wilson's disease (WD). We aimed to report on the long-term outcome of WD patients following LT. METHODS: The medical records of 121 French patients transplanted for WD between 1985 and 2009 were reviewed retrospectively. Seventy-five patients were adults (median age: 29 years, (18-66)) and 46 were children (median age: 14 years, (7-17)). The indication for LT was (1) fulminant/subfulminant hepatitis (n = 64, 53%), median age = 16 years (7-53), (2) decompensated cirrhosis (n = 50, 41%), median age = 31.5 years (12-66) or (3) severe neurological disease (n = 7, 6%), median age = 21.5 years (14.5-42). Median post-transplant follow-up was 72 months (0-23.5). RESULTS: Actuarial patient survival rates were 87% at 5, 10, and 15 years. Male gender, pre-transplant renal insufficiency, non elective procedure, and neurological indication were significantly associated with poorer survival rate. None of these factors remained statistically significant under multivariate analysis. In patients transplanted for hepatic indications, the prognosis was poorer in case of fulminant or subfulminant course, non elective procedure, pretransplant renal insufficiency and in patients transplanted before 2000. Multivariate analysis disclosed that only recent period of LT was associated with better prognosis. At last visit, the median calculated glomerular filtration rate was 93 ml/min (33-180); 11/93 patients (12%) had stage II renal insufficiency and none had stage III. CONCLUSIONS: Liver failure associated with WD is a rare indication for LT (<1%), which achieves an excellent long-term outcome, including renal function.

Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial.

BACKGROUND: Albumin dialysis with the Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden), a noncell artificial liver support device, may be beneficial in acute liver failure (ALF). OBJECTIVE: To determine whether MARS improves survival in ALF. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT00224705). SETTING: 16 French liver transplantation centers. PATIENTS: 102 patients with ALF. INTERVENTION: Conventional treatment (n = 49) or MARS with conventional treatment (n = 53), stratified according to whether paracetamol caused ALF. MEASUREMENTS: 6-month survival and secondary end points, including adverse events. RESULTS: 102 patients (mean age, 40.4 years [SD, 13]) were in the modified intention-to-treat (mITT) population. The per-protocol analysis (49 conventional, 39 MARS) included patients with at least 1 session of MARS of 5 hours or more. Six-month survival was 75.5% (95% CI, 60.8% to 86.2%) with conventional treatment and 84.9% (CI, 71.9% to 92.8%) with MARS (P = 0.28) in the mITT population and 75.5% (CI, 60.8% to 86.2%) with conventional treatment and 82.9% (CI, 65.9% to 91.9%) with MARS (P = 0.50) in the per-protocol population. In patients with paracetamol-related ALF, the 6-month survival rate was 68.4% (CI, 43.5% to 86.4%) with conventional treatment and 85.0% (CI, 61.1% to 96.0%) with MARS (P = 0.46) in the mITT population. Sixty-six of 102 patients had transplantation (41.0% among paracetamol-induced ALF; 79.4% among non-paracetamol-induced ALF) (P < 0.001). Adverse events did not significantly differ between groups. LIMITATION: The short delay from randomization to liver transplantation (median, 16.2 hours) precludes definitive efficacy or safety evaluations. CONCLUSION: This randomized trial of MARS in patients with ALF was unable to provide definitive efficacy or safety conclusions because many patients had transplantation before administration of the intervention. Acute liver failure not caused by paracetamol was associated with greater 6-month patient survival. PRIMARY FUNDING SOURCE: Assistance Publique-Hôpitaux de Paris.