Osteoporosis and Fragility Fractures in Patients With Cirrhosis Evaluated for Liver Transplantation: Identification of High-Risk Patients Based on Computed Tomography at Evaluation.

INTRODUCTION: Osteoporosis in candidates for liver transplantation (LT) is often underdiagnosed despite the important consequences of morbidity. METHODS: We included 376 patients with cirrhosis evaluated for LT with available computed tomography (CT) scans. Prevalent vertebral fractures (VFs) were identified on CT reconstructions, and bone density was assessed by measuring CT attenuation of the L1 vertebra (L1-CT). RESULTS: We identified 139 VFs in 55 patients (14.6%). Logistic regression models showed that low L1-CT was the only independent determinant of VF. DISCUSSION: In patients with cirrhosis evaluated for LT, CT scans identified persons with severe osteoporosis without additional costs.

Autoimmune hepatitis recurrence after liver transplantation: "Les jeux sont faits".

Autoimmune hepatitis (AIH) may recur after liver transplantation (LT). The aims of this study were to evaluate the incidence and risk factors for recurrent autoimmune hepatitis (rAIH). A multicenter retrospective French nationwide study, including all patients aged ≥16 transplanted for AIH, with at least 1 liver biopsy 1 year after LT, was conducted between 1985 and 2018. Risk factors for rAIH were identified using a multivariate Cox regression model. Three hundred and forty-four patients were included (78.8% women) with a median age at LT of 43.6 years. Seventy-six patients (22.1%) developed recurrence in a median time of 53.6 months (IQR, 14.1-93.2). Actuarial risk for developing rAIH was 41.3% 20 years after LT. In multivariate analysis, the strongest risk factor for rAIH was cytomegalovirus D+/R- mismatch status (HR=2.0; 95% CI: 1.1-3.6; p =0.03), followed by associated autoimmune condition. Twenty-one patients (27.6% of rAIH patients) developed liver graft cirrhosis after rAIH. Independent risk factors for these severe forms of rAIH were young age at LT, IgG levels >20.7 g/L, and LT in the context of (sub)fulminant hepatitis. Immunosuppression, especially long-term maintenance of corticosteroid therapy, was not significantly associated with rAIH. Recurrence of AIH after LT is frequent and may lead to graft loss. Recurrence is more frequent in young patients with active disease at the time of LT, yet systematic corticosteroid therapy does not prevent it.

Identification of Semiochemical Candidates Involved in Glossina Palpalis Gambiensis Larviposition Site Selection and Behavioural Responses of Adult Gravid Females.

Tsetse flies (Diptera: Glossinidae) are the cyclical vectors of human and animal trypanosomes. This viviparous insect develops and produces a single larva at 10-day intervals deposited in specific sites. In some species aggregation of larvae has been shown and seems to be mediated by both physical factors and volatile semiochemicals of larval origin. In this context, this study aims to identify chemicals emitted during the pupariation process in Glossina palpalis gambiensis. Volatile Organic Compounds (VOCs) emitted by larvae were identified using static headspace solid-phase microextraction and gas-chromatography mass-spectrometry (GC-MS) analysis. Electrophysiology and behavioural assays were performed on gravid females to confirm VOCs behavioural activity and attractiveness. GC-MS results revealed ten chemicals emitted during the pupariation process of G. p. gambiensis larvae. Among these chemicals, gravid females were shown to detect nine of them during coupled gas chromatography - electroantennographic detection tests. Behavioural assays highlighted two compounds were as attractive as pupae and one compound and a blend of four compounds were more attractive than pupae. Although the larval origin of some of them needs to be confirmed as they may also likely produced by micro-organisms, these compounds induced significant behavioural responses in the laboratory. Further experiments have to explore the biological activity and competitiveness of these compounds in the field. This work opens interesting opportunities for behavioural manipulation and control of tsetse flies.

Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.

Refining Auxiliary Orthotopic Liver Transplantation (AOLT) Improves Outcomes in Adult Patients With Acute Liver Failure.

OBJECTIVE: To investigate whether and how experience accumulation and technical refinements simultaneously implemented in auxiliary orthotopic liver transplantation (AOLT) may impact on outcomes. BACKGROUND: AOLT for acute liver failure (ALF) provides the unique chance of complete immunosuppression withdrawal after adequate native liver remnant regeneration but is a technically demanding procedure. Our department is a reference center for ALF and an early adopter of AOLT. METHODS: This is a single-center retrospective before/after study of a prospectively maintained cohort of 48 patients with ALF who underwent AOLT between 1993 and 2019. In 2012, technical refinements were implemented to improve outcomes: (i) favoring the volume of the graft rather than that of the native liver, (ii) direct anastomosis of graft hepatic artery with recipient right hepatic artery instead of the use of large size vessels, (iii) end-to-side hepaticocholedocostomy instead of bilioenteric anastomosis. Early experience (1993-2011) group (n=26) and recent experience (2012-2019) group (n=22) were compared. Primary endpoint was 90-day severe morbidity rate (Clavien-Dindo≥IIIa) and secondary endpoints were overall patient survival and complete immunosuppression withdrawal rates. RESULTS: Compared with the earlier experience group, the recent experience group was associated with a lower severe complication rate (27% vs 65%, P <0.001), as well as less biliary (18% vs 54%, P =0.017) and arterial (0% vs 15%, P =0.115) complications. The 1-, 3-, and 5-year patient survival was significantly improved (91%, 91%, 91% vs 76%, 61%, 60%, P =0.045). The rate of complete immunosuppression withdrawal increased to 94% vs 70%, ( P =0.091) with no need of long-term graft explant. CONCLUSION: These technical refinements favoring the liver graft and reducing morbidity may promote AOLT implementation among LT centers.

Liver transplantation for autoimmune hepatitis: Pre-transplant does not predict the early post-transplant outcome.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a rare indication (<5%) for liver transplantation (LT). The aim of this study was to describe the early outcome after LT for AIH. METHODS: A multicenter retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Occurrences of biliary and vascular complications, rejection, sepsis, retransplantation and death were collected during the first year after LT. RESULTS: A total of 344 patients (78.8% of women, 17.0% of (sub)fulminant hepatitis and 19.2% of chronic liver diseases transplanted in the context of acute-on-chronic liver failure [ACLF]) were included, with a median age at LT of 43.6 years. Acute rejection, sepsis, biliary and vascular complications occurred in respectively 23.5%, 44.2%, 25.3% and 17.4% of patients during the first year after LT. One-year graft and patient survivals were 84.3% and 88.0% respectively. The main cause of early death was sepsis. Pre-LT immunosuppression was not associated with an increased risk for early infections or surgical complications. Significant risk factors for septic events were LT in the context of (sub)fulminant hepatitis or ACLF, acute kidney injury at the time of LT (AKI) and occurrence of biliary complications after LT. AKI was the only independent factor associated with graft (HR = 2.5; 95% CI: 1.1-5.4; p = .02) and patient survivals (HR = 2.6; 95% CI: 1.0-6.5; p = .04). CONCLUSION: Early prognosis is good after LT for AIH and is not impacted by pre-LT immunosuppression but by the presence of AKI at the time of LT.

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years.

BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH). METHODS: A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded. RESULTS: The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4-53.8). Median follow-up was 87.0 months (IQR, 43.5-168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4-6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2-5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5-5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4-6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2-3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0-3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2-3.5; p = 0.006) complications. CONCLUSION: Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.

Evaluation of transcranial Doppler use in patients with acute liver failure listed for emergency liver transplantation.

PURPOSE: Acute liver failure (ALF) is characterized by hepatic encephalopathy (HE) often due to intracranial hypertension (ICH). The risk/benefit-balance of intraparenchymal pressure catheter monitoring is controversial during ALF. AIMS: Perform an evaluation of transcranial Doppler (TCD) use in patients with ALF listed for emergency liver transplantation. MATERIAL AND METHODS: Single center retrospective cohort study including all patients registered on high emergency LT list between 2012 and 2018. All TCD measurements performed during ICU stay after listing and after LT (when performed) were recorded. TCD was considered abnormal when pulsatility index (PI) was >1.2. RESULTS: Among 106 patients with ALF, forty-seven (44%) had a TCD while on list. They had more severe liver and extrahepatic organ failure. When performed, TCD was abnormal in 51% of patients. These patients more frequently developed ICH events (45% vs. 13%, p = .02) and more frequently required increase in sedative drugs and vasopressors. While 22% of patients with normal TCD spontaneously survived, all of those with abnormal TCD died or were transplanted (p = .02). All transplanted patients who had abnormal exams normalized their TCD within 2 (1-2) days after LT. CONCLUSION: TCD may be a useful non-invasive tool for ICH detection and management, then guide sedation withdrawal.

Enterococcal pyogenic liver abscesses: high risk of treatment failure and mortality.

Enterococci are the most frequent gram-positive bacteria recovered from pyogenic liver abscesses (PLA). This study aims to analyze the impact of the presence of Enterococcus spp. on PLA outcome. We retrospectively analyzed the characteristics and outcome of all PLA cases in which Enterococcus spp. was isolated between January 2010 and September 2019 in a French university hospital and compared them to PLA without Enterococcus spp. Enterococci were recovered from 68 of the 359 (19%) PLA cases. Among the 78 isolates, Enterococcus faecalis (n = 37, 47.7%) and Enterococcus faecium (n = 32, 41%) were the most frequent. Enterococcal PLA were more often of biliary origin (79.4% versus 54.6%, p < 0.001) or post-surgical (35.3% versus 18.6%, p = 0.004). Multivariate analysis showed an independent association between the isolation of Enterococcus spp. and 3-month mortality (HR 2.51, p = 0.011), primary failure (HR 2.15, p = 0.006), but not with relapses (HR 0.86, p = 0.739). In the subgroup of enterococcal PLA, portal vein thrombosis was the only factor significantly associated with 3-month mortality (univariate HR 3.45, p = 0.023) or primary treatment failure (multivariate, HR 4.02, p = 0.006). Enterococcus spp. identification in a PLA is associated with a higher mortality and primary treatment failure.

Analysis of 15 cases from a monocentric cohort of 307 liver abscesses.

BACKGROUND: Out of the context of haematological patients, Candida sp. is rarely retrieved from pyogenic liver abscesses (PLA). OBJECTIVES: Our objective was to assess the risk factors for occurrence, and clinical, microbiological characteristics, management and outcome of Candida pyogenic liver abscesses (C-PLA). PATIENTS/METHODS: We retrospectively analysed C-PLA cases and compared them to pyogenic liver abscesses exclusively due to bacteria (B-PLA) included in our monocentric database on liver abscesses. Unfavourable course was defined as the occurrence of a primary treatment failure (PTF), recurrence after an initial cure, or death within 3 months after diagnosis. RESULTS: Between 2010 and 2018, 15 C-PLA and 292 B-PLA were included. All C-PLA had a biliary origin and were polymicrobial. All patients with C-PLA had at least one comorbidity at risk for Candida infection and 7 (53.3%) presented with sepsis requiring an admission in intensive care unit. Median duration of antifungal treatment was 42 days [24-55]. In multivariate analysis, compared with B-PLA, a medical history of malignancy (OR 4.16; 95%CI 1.15-18.72) or liver abscess (OR 7.39; 95%CI 2.10-26.62), and sepsis with severity criteria (OR 3.52; 95%CI 1.07-11.90) were independently associated with the occurrence of C-PLA. In multivariate analysis, C-PLA was associated with a higher risk of recurrence (HR 3.08; 95%CI 1.38-11.22). CONCLUSION: Candida liver abscesses in non-neutropenic is a rare and severe disease. The high rate of recurrence should lead to discuss a more intensive treatment.

Laparoscopic-assisted liver transplantation: A realistic perspective.

Laparoscopic approach was rarely described in recipients for liver transplantation (LT). We report the feasibility and safety of laparoscopic-assisted LT (LA-LT) in patients with unresectable liver metastases of neuroendocrine tumors. Total hepatectomy was performed laparoscopically with graft implantation through an upper midline incision. Liver grafts were retrieved from deceased donors. From July 2019 to July 2021, six patients (4 women, 2 men) underwent LA-LT. Median age and BMI were 46 (29-54) and 24 (19-35) kg/m2 , respectively. Implanted grafts were reduced (n = 3), full (n = 2), and a right split liver (n = 1). Median surgical time was 405 min (390-450) and median blood loss was 425 ml (250-600). Median cold and warm ischemia times were 438 min (360-575) and 35 min (30-40), respectively. Median anhepatic phase was 51 min (40-67) and midline incision was 14 cm (13-20) long. On postoperative day 5, median prothrombin index and serum bilirubin levels were 95% (70-117) and 11 (10-37) µmol/L, respectively. No Clavien-Dindo > III complications were encountered. Median hospital stay was 12 days (10-14). After a median follow-up of 8 (8-32) months, all patients were alive without tumor recurrence or adverse event. This preliminary series suggests that in selected patients, LA-LT is a safe and effective option.

Behavioural analysis of swarming mosquitoes reveals high hearing sensitivity in Anopheles coluzzii.

Mosquitoes of many species mate in station-keeping swarms. Mating chases ensue as soon as a male detects the flight tones of a female with his auditory organs. Previous studies of hearing thresholds have mainly used electrophysiological methods that prevent the mosquito from flying naturally. The main aim of this study was to quantify behaviourally the sound level threshold at which males can hear females. Free-flying male Anopheles coluzzii were released in a large arena (∼2 m high×2 m×1 m) with a conspicuous object on the ground that stimulated swarming behaviour. Males were exposed to a range of natural and synthetic played-back sounds of female flight. We monitored the responses of males and their distance to the speaker by recording changes in their wingbeat frequency and angular speed. We show that the mean male behavioural threshold of particle velocity hearing lies between 13 and 20 dB sound particle velocity level (SVL) (95% confidence interval). A conservative estimate of 20 dB SVL (i.e. <0.5 µm s-1 particle velocity) is 12-26 dB lower than most of the published electrophysiological measurements from the Johnston's organ. In addition, we suggest that (1) the first harmonic of a female's flight sound is sufficient for males to detect her presence, (2) males respond with a greater amplitude to single-female sounds than to the sound of a group of females and (3) the response of males to the playback of the flight sound of a live female is the same as to that of a recorded sound of constant frequency and amplitude.

Large retrospective study analysing predictive factors of primary treatment failure, recurrence and death in pyogenic liver abscesses.

PURPOSE: Pyogenic liver abscess (PLA) is a severe disease, which unfavourable evolution remains frequent. Our objective was to assess predictive factors of unfavourable outcome in patients with PLA. METHODS: We conducted a retrospective study in a French tertiary care centre. All patients admitted for PLA between 2010 and 2018 were included. Unfavourable course was defined as the occurrence of a primary treatment failure (PTF), recurrence of PLA after an initial cure, or death within 3 months after diagnosis. Hazard ratios (95% CI) were calculated with multivariable Cox proportional hazard models. RESULTS: 302 patients were included among which 91 (30.1%) patients had an unfavourable outcome because of PTF, recurrence or death in 55 (18.2%), 28 (9.2%) and 32 (10.6%) patients, respectively. Hepatic metastases (HR 2.08; 95% CI 1.04-4.15), a nosocomial infection (2.25; 1.14-4.42), portal thrombosis (2.12; 1.14-3.93), and the isolation of Enterococcus spp. (2.18; 1.22- 3.90) were independently associated with PTF. Ischemic cholangitis (6.30; 2.70-14.70) and the isolation of Streptococcus spp. (3.72; 1.36-10.16) were associated with the risk of recurrence. Charlson comorbidity index (HR 1.30 per one point; 95% CI 1.15-1.46; p < 0.001), portal thrombosis (3.53; 1.65-7.56) and the presence of multi-drug-resistant organisms (3.81; 1.73-8.40) were associated with mortality within 3 months following PLA diagnosis. PLA drainage was the only factor associated with a lower mortality (0.14; 0.06-0.34). CONCLUSION: Identification of specific risk factors may help to improve the management of PLA and to elaborate targeted recommendations according to patient's and disease's characteristics.

[An update on some atypical electrocardiographic forms of acute coronary syndrome The "STEMI equivalents"]. / Mise au point sur certaines formes électrocardiographiques atypiques du syndrome coronarien aigu - « Équivalents STEMI ¼.

The diagnosis of acute coronary syndrome with ST segment elevation (STEMI) is based on clinical symptoms suggestive of acute myocardial ischemia and precise ECG criteria. STEMI is due to an acute occlusion or subocclusion of a coronary artery, generating a transmural ischaemia, requiring coronary angiography with urgent coronary revascularization. However, some authors consider the current STEMI ECG criteria to be too restrictive: up to 30 % of patients who do not meet these criteria present with critical coronary artery stenosis or acute coronary occlusion. Atypical electrocardiographic patterns, known as "STEMI equivalents", can be found in some cases and justify a rapid cardiological evaluation. We present a pragmatic review of five STEMI equivalents.

Le diagnostic de syndrome coronarien aigu avec sus-décalage du segment ST (ST-Elevation Myocardial Infarction (STEMI)) est basé sur une clinique évocatrice d'une ischémie myocardique et des critères ECG précis. Le STEMI est le reflet d'une (sub)occlusion aiguë d'une artère coronaire engendrant une ischémie transmurale, nécessitant une coronarographie avec un geste de revascularisation en urgence. Certains auteurs considèrent les critères ECG actuels du STEMI comme étant trop restrictifs : jusqu'à 30 % des patients ne remplissant pas ces critères présenteraient une sténose coronarienne critique ou une occlusion coronarienne aiguë. Des aspects électrocardiographiques atypiques, dits « équivalents STEMI ¼, peuvent être mis en évidence dans certains cas et justifient une prise en charge cardiologique rapide. Nous présentons une revue pragmatique de cinq équivalents STEMI.

[Cardiology]. / Cardiologie.

Significant advances have been made in 2021 in the areas of interventional cardiology, heart failure, cardiac imaging, electrophysiology and congenital heart disease. In addition to improving the screening, diagnosis and management of many heart diseases, these advances will change our daily practice. Moreover, the European Society of Cardiology has updated its guidelines on heart failure, valve disease, cardiac pacing and cardiovascular disease prevention. As in previous years, members of the Cardiology division of Lausanne University Hospital (CHUV) came together to select and present to you the papers that they considered to be the most important of the past year.

De nombreux progrès ont été réalisés en 2021 dans les domaines de la cardiologie interventionnelle, de l'insuffisance cardiaque, de l'imagerie cardiaque, de l'électrophysiologie et des cardiopathies congénitales. En plus d'améliorer le dépistage, le diagnostic et la prise en charge de nombreuses cardiopathies, ces avancées vont faire évoluer notre pratique quotidienne. Par ailleurs, la Société européenne de cardiologie a mis à jour ses recommandations portant sur l'insuffisance cardiaque, les valvulopathies, la stimulation cardiaque et la prévention des maladies cardiovasculaires. Comme les années précédentes, les membres du Service de cardiologie du CHUV se sont réunis pour sélectionner et vous présenter les travaux qui leur ont semblé être les plus importants de l'année écoulée.

Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium.

Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.

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.

A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis.

BACKGROUND: Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator-activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition. METHODS: In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid. The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months. RESULTS: The primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P<0.001). Normal levels of alkaline phosphatase were observed in 67% of the patients in the bezafibrate group and in 2% in the placebo group. Results regarding changes in pruritus, fatigue, and noninvasive measures of liver fibrosis, including liver stiffness and Enhanced Liver Fibrosis score, were consistent with the results of the primary outcome. Two patients in each group had complications from end-stage liver disease. The creatinine level increased 5% from baseline in the bezafibrate group and decreased 3% in the placebo group. Myalgia occurred in 20% of the patients in the bezafibrate group and in 10% in the placebo group. CONCLUSIONS: Among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy. (Funded by Programme Hospitalier de Recherche Clinique and Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731 .).

Acute-on-chronic liver failure: Where do we stand?

Acute-on-chronic liver failure (ACLF) is defined by the rapid development of organ(s) failure(s) associated with high rates of early (28-day) mortality in patients with cirrhosis. ACLF has been categorized into three grades of increasing severity according to the nature and number of organ failures. In patients with grade 3 ACLF, 28-day mortality is >70%. While the definition of ACLF has been endorsed by European scientific societies, North American and Asian Pacific associations have proposed alternative definitions. A prognostic score called the CLIF-C ACLF score provides a more precise assessment of the prognosis of patients with ACLF. Although bacterial infections and variceal bleeding are common precipitating factors, no precipitating factor can be identified in almost 60% of patients with ACLF. There is increasing evidence that cirrhosis is a condition characterized by a systemic inflammatory state and occult infections or translocation of bacteria or bacterial products from the lumen of the GUT to the systemic circulation which could play a role in the development of ACLF. Simple and readily available variables to predict the occurrence of ACLF in patients with cirrhosis have been identified and high-risk patients need careful management. Whether prolonged administration of statins, rifaximin or albumin can prevent ACLF requires further study. Patients with organ(s) failure(s) may needed to be admitted to the ICU and there should be no hesitation in admitting patients with cirrhosis to the ICU. No benefit to survival was observed with albumin dialysis and rescue transplantation is the best option in the most severe patients. One-year post-transplant survival rates exceeding 70%-75% have been reported, including in patients with grade 3 ACLF but these patients were highly selected. Criteria have been proposed to define futile transplantation (too ill to be transplanted), but these criteria need to be refined to include age, comorbidities and frailty in addition to markers of disease severity.

Impact of cardiac function, refractory ascites and beta blockers on the outcome of patients with cirrhosis listed for liver transplantation.

BACKGROUND & AIMS: Whether non-selective beta blockers (NSBBs) are deleterious in patients with end-stage cirrhosis and refractory ascites has been widely debated. We hypothesized that only the subset of patients on the liver transplant waiting list who had impaired cardiac performance would be at increased risk of mortality if receiving NSBBs. METHODS: This study included 584 consecutive patients with cirrhosis evaluated for transplantation between 1999 and 2014. All patients had right heart catheterization with hemodynamic measurements at evaluation. Fifty percent received NSBBs. Refractory ascites was present in 33%. Cardiac performance was assessed by left ventricular stroke work index (LVSWI). Waiting list mortality without liver transplantation was explored using competing risk analysis. RESULTS: LVSWI was significantly lower in patients with refractory ascites. In multivariate analysis using competing risk, refractory ascites, NSBBs and LVSWI were associated with waiting list mortality in the whole population, with a statistically significant interaction between NSBBs and LVSWI. The most discriminant value of LVSWI was 64.1 g-m/m2. In the final model, refractory ascites (subdistribution hazard ratio 1.52; 95% CI1.01-2.28; p = 0.0083) and treatment by NSBBs with LVSWI <64.1 g-m/m2 (subdistribution hazard ratio 1.96; 95% CI 1.32-2.90; p = 0.0009) were significantly associated with waiting list mortality, taking into account serum sodium and the model for end-stage liver disease score. CONCLUSIONS: This study suggests that compromised cardiac performance is more common in patients with refractory ascites and that NSBBs are deleterious in cirrhotic patients with compromised cardiac performance. These results highlight the prognostic value of cardiac function in patients with end-stage cirrhosis. LAY SUMMARY: There are still controversies concerning the impact of non-selective beta blockers on outcomes in patients with decompensated cirrhosis, especially in those with refractory ascites. In this study of 584 cirrhotic patients evaluated for liver transplantation, who underwent right heart catheterization, we have shown that global cardiac performance measured by left ventricular stroke work index is lower in patients with refractory ascites. Administration of non-selective beta blockers in patients with compromised cardiac performance may increase waiting list mortality. These results highlight the prognostic value of global cardiac performance in patients with end-stage cirrhosis.