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Purpose: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure.Methods: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence.Results: We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain.Conclusions: ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes. [ABSTRACT FROM AUTHOR]

Résumé: La décompensation de la cirrhose dans sa forme ACLF (acronyme anglo-saxon pour Acute On Chronic Liver Failure) est de prise en charge complexe et de mauvais pronostic en raison de la présence de défaillance d'organes. L'ACLF a été définie en 2013 comme un syndrome se développant chez un patient présentant une maladie hépatique chronique, caractérisé par une insuffisance hépatique associée à, au moins, une défaillance d'un autre organe. Son classement en plusieurs grades de sévérité croissante est associé à la mortalité sans transplantation hépatique (TH). L'ACLF doit être considéré comme un syndrome dynamique et l'appréciation de sa sévérité doit être évaluée dans la semaine qui suit l'admission. L'inflammation est un acteur central de sa physiopathologie au cours de la cirrhose. Le mauvais pronostic à court terme des formes graves d'ACLF peut faire discuter la TH en procédure accélérée chez des patients très sélectionnés. Les scores pronostiques de gravité de la cirrhose (scores de Child-Pugh et de MELD) ne sont pas adaptés à cette entité et, pour l'instant, c'est le score CLIF-C-ACLF qui possède la meilleure capacité de prédiction de la mortalité chez les patients cirrhotiques. The decompensation of cirrhosis in ACLF (acronym of Acute On Chronic Liver Failure) is challenging in terms of management and has poor prognosis because of organs failure. ACLF was defined in 2013 as a syndrome developing in patient with chronic liver disease, characterized by acute hepatic decompensation associated, at least, with one other organ failure. Its classification in several grades of increasing severity is associated with mortality without liver transplantation (LT). The ACLF must be considered as a dynamic syndrome and the assessment of its severity have to be evaluated within one week of admission. Inflammation is a central actor of its pathophysiology during cirrhosis. The poor short-term prognosis of severe ACLF can lead to discuss LT in an accelerated course in highly selected patients. The prognosis scores of cirrhosis (Child Pugh and MELD scores) are not adapted to this entity and for the moment it is the CLIF-C-ACLF score which provides the best capacity for predicting mortality in cirrhotic patients. [ABSTRACT FROM AUTHOR]

Background: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute liver decompensation with extrahepatic organ failure in patients with pre-existing liver disease causing high short-term mortality. A good knowledge about characteristics and diagnostic of ACLF will help us to give proper treatment. The aim of this study is to know the profile and characteristics of ACLF patient Method: Retrospective study was conducted to find patient with ACLF between January 2017-January 2018 at Fatmawati General Hospital. Results: Ten patients were diagnosed with ACLF. Six patients admitted with a chief complaint: unconscious, 2 of them had hematemesis in the course-of-treatment. Three patients were admitted with abdominal pain, and 1 patient with hematemesis-melena. Seven patients had hepatitis-B infection. Aspartate-transaminase to platelet-ratio index (APRI) values varied (median 8.1; minimum 2.81 -maximum 34.67). Hepatic encephalopathy, ascites, and acute renal failure were found in 90% of patients. Jaundice can be found in all patients, with mean values ofbilirubin levels inpatients undergoing test for bilirubin level were 18.56 mg/dL (9/10). Coagulation disorders were found in 60% of patients undergoing haemostasis test. Four patients were diagnosed with grade 3 ACLF. All ACLF patients eventually died during treatment, including third-degree patients who all died within 7 days. Only 2 patients survived more than 7 days, and 4 patients died within 3 days of treatment. Conclusion: mortality rates of ACLF were very high, and are often found in patients with advanced liver disease characterized by high APRI values. The prognosis is related to the number of organ failures. Central nervous system, kidneys and liver are the organs that are often impaired. Because the current treatment method is still limited, further research is needed, especially on biomarkers for better prevention, diagnosis and treatment. [ABSTRACT FROM AUTHOR]

International club of ascites (ICA) has introduced revised criteria for hepatorenal syndrome—acute kidney injury (HRS-AKI) with an aim to improve the response rate to treatment. We lack prospective trials to assess its positive impact on the response rate and factors influencing response rate. Thus, we conducted this study with the primary aim of identifying independent factors that predict treatment response to terlipressin. We prospectively included patients of HRS-AKI as per the revised ICA criteria. All were treated with terlipressin and albumin according to the defined protocol and were followed for 90 days, death or liver transplantation. Baseline parameters, as well as delta serum creatinine (sCr) at day 4 (DCD4), were investigated as predictive factors influencing response to terlipressin (primary endpoint). Secondary endpoints were the overall response rate to terlipressin, response in various subgroups of acute-on-chronic liver failure (ACLF) patients, need for readmission, and 90 days survival. The study included 114 patients with a median age of 52 years (83% males). 70 (61%) patients responded to terlipressin. Response rate among ACLF1, ACLF2, and ACLF3 were 62%, 48%, and 35%, respectively. On multivariate analysis, baseline creatinine (odds ratio [OR] 7.889, 95% confidence interval [CI] 3.335, 18.664), Child Turcotte Pugh (CTP) score (OR 1.470, 95% CI 1.026, 2.106), and the DCD4 (OR 0.048, 95% CI 0.015, 0.158) were independently predicting response. We also created a Delhi Model (DM) with an excellent predictive ability for response prediction at day 4 with an AUROC of 0.940 (95% CI 0.897, 0.982). Among responder group, 50% of patients required readmission within three months. The 90-days survival among responder and non-responder groups were 68.5% and 9% (P value < 0.01), respectively. Baseline creatinine, CTP score, and DCD4 independently predict response to terlipressin in HRS-AKI. The DM may guide terlipressin treatment in HRS-AKI but needs further validation. [Display omitted] • The international club of ascites recently introduced revised criteria for Hepatorenal Syndrome Acute Kidney Injury (HRS-AKI) to improve treatment outcome. • Our study showed overall 61% response rate to terlipressin treatment. Response in acute decompensation was better than acute on chronic liver failure 80% vs. 40%, respectively. • Delhi model (DM) created based on three independent parameters (baseline serum creatinine Child Turcotte Pugh and delta creatinine at day 4) to predict response at day 4 of treatment demonstrated high sensitivity and specificity with an area under the receiver operating characteristic curve (AUROC) of 0.940. • DM will be helpful in clinical practise to predict response to terlipressin treatment and to filter non responder candidates at day 4 of treatment. [ABSTRACT FROM AUTHOR]

Cholemic nephropathy (CN) is a recognized cause of acute kidney injury (AKI) in patients with severe hyperbilirubinemia (sHyb) and jaundice. Pathophysiological mechanisms of CN are not completely understood, but it seems caused both by direct toxicity of cholephiles and bile casts formation in nephrons enhanced by prolonged exposure to sHyb, particularly in the presence of promoting factors, as highlighted by a literature reviewed and by personal experience. The aim of our update is to retrace CN in its pathophysiology, risk factors, diagnosis and treatment, underlining the role of sHyb, promoting factors, and CN-AKI diagnostic criteria in the different clinical settings associated with this often-concealed disease. Our purpose is to focus on clinical manifestation of CN, exploring the possible transition to CKD. Cholemic nephropathy is an overlooked clinical entity that enters differential diagnosis with other causes of AKI. Early diagnosis and treatment are essential because renal injury could be fully reversible as rapidly as bilirubin levels are reduced. In conclusion, our proposal is to introduce an alert for considering CN in diagnostic and prognostic scores that include bilirubin and/or creatinine with acute renal involvement, with the aim of early diagnosis and treatment of sHyb to reduce the burden on renal outcome.

Competing Interests: Michael Praktiknjo has received speaking fees from Gore. Jonel Trebicka has received speaking and/or consulting fees from Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit and CSL Behring. Please refer to the accompanying ICMJE disclosure forms for further details.

Background: Taraxacum officinale (TO) or dandelion has been frequently used to prevent or treat different liver diseases because of its rich composition in phytochemicals with demonstrated effect against hepatic injuries. This study aimed to investigate the possible preventing effect of ethanolic TO root extract (TOERE) on a rat experimental acute on chronic liver failure (ACLF) model. Methods: Chronic liver failure (CLF) was induced by human serum albumin, and ACLF was induced in CLF by D-galactosamine and lipopolysaccharide (D-Gal-LPS). Five groups (n = 5) of male Wistar rats (200–250 g) were used: ACLF, ACLF-silymarin (200 mg/kg b.w./day), three ACLF-TO administered in three doses (200 mg, 100 mg, 50 mg/kg b.w./day). Results: The in vivo results showed that treatment with TOERE administered in three chosen doses before ACLF induction reduced serum liver injury markers (AST, ALT, ALP, GGT, total bilirubin), renal tests (creatinine, urea), and oxidative stress tests (TOS, OSI, MDA, NO, 3NT). Histopathologically, TOERE diminished the level of liver tissue injury and 3NT immunoexpression. Conclusions: This paper indicated oxidative stress reduction as possible mechanisms for the hepatoprotective effect of TOERE in ACLF and provided evidence for the preventive treatment.

Renal dysfunction is a common, life-threatening complication occurring in patients with liver disease. Hepatorenal syndrome (HRS) has been defined as a purely "functional" type of renal failure that often occurs in patients with cirrhosis in the setting of marked abnormalities in arterial circulation, as well as overactivity of the endogenous vasoactive systems.4,5 In 2007, the International Club of Ascites (ICA) classified HRS into types 1 and 2 (HRS-1 and HRS-2).5 HRS-1 is characterised by a rapid deterioration of renal function that often occurs because of a precipitating event, while HRS-2 is a moderate and stable or slowly progressive renal dysfunction that often occurs without an obvious precipitant. Clinically, HRS-1 is characterised by acute renal failure while HRS-2 is mainly characterised by refractory ascites. Nevertheless, after these two entities were first described, new concepts, definitions, and diagnostic criteria have been developed by nephrologists for renal dysfunction in the general population and hospitalised patients. In particular, the definitions and characterisation of acute kidney injury (AKI), acute kidney disease and chronic kidney disease have been introduced/refined.6 Accordingly, a debate among hepatologists of the ICA led to a complete revision of the nomenclature and diagnosistic criteria for HRS-1, which was renamed HRS-AKI.7 Additionally, over recent years, greater granularity has been gained regarding the pathogenesis of HRS; it is now increasingly recognised that it is not a purely "functional" entity with haemodynamic derangements, but that systemic inflammation, oxidative stress and bile salt-related tubular damage may contribute significantly to its development. That is, HRS has an additional structural component that would not only make traditional diagnostic criteria less reliable, but would explain the lack of response to pharmacological treatment with vasoconstrictors plus albumin that correlates with a progressive increase in inflammation. Because classification, nomenclature, diagnostic criteria and pathogenic theories have evolved over the years since the traditional classification of HRS-1 and HRS-2 was first described, it was considered that all these novel aspects be reviewed and summarised in a position paper. The aim of this position paper authored by two hepatologists (members of ICA) and two nephrologists involved in the study of renal dysfunction in cirrhosis, is to complete the re-classification of HRS initiated by the ICA in 2012 and to provide an update on the definition, classification, diagnosis, pathophysiology and treatment of HRS. [ABSTRACT FROM AUTHOR]

Background and Aims: The long‐term outcomes of patients with hepatitis B virus‐related acute on chronic liver failure (HBV‐ACLF) remain unclear. The main aim of the study was to compare the 5‐year survival rate and incidence rate of hepatocellular carcinoma (HCC) between patients with HBV‐ACLF and HBV‐cirrhosis. Methods: Clinical data of patients with ACLF, compensated cirrhosis and decompensated cirrhosis who survived more than 3 months after diagnosis were collected. The survival rate and cumulative incidence of HCC were compared. The Cox regression was used to evaluate risk factors for outcomes. Results: A total of 814 patients were included in the analysis, including 122 (14.99%) patients with ACLF, 450 (55.28%) patients with compensated cirrhosis and 242 (29.73%) patients with decompensated cirrhosis. The 5‐year survival rate of patients with ACLF (97.2%) was higher than patients with decompensated cirrhosis (86.0%), but was lower than patients with compensated cirrhosis (99.1%). The 5‐year HCC incidence rate was the highest in the decompensated cirrhosis group (14.6%, P < 0.05), while no statistical differences were found between patients with ACLF (3.5%) and compensated cirrhosis (9.5%). The episode of ACLF did not increase the risk of HCC and the overall survival when compared with patients with cirrhosis. In ACLF subgroup analysis, the age, rather than the presence of cirrhosis, was independently associated with both mortality and incidence of HCC. Conclusions: ACLF patients who survived the first 3 months had a better long‐term prognosis than decompensated cirrhosis, while the HCC risk was comparable to compensated cirrhosis. HCC surveillance is strongly recommended for these patients. [ABSTRACT FROM AUTHOR]

Background: The clinical course of acutely decompensated cirrhosis (AD) is heterogeneous. Presepsin (PSP) is a plasmatic biomarker that reflects Toll-like receptor activity and systemic inflammation. We conducted a prospective study to: (1) measure PSP in AD and (2) assess whether PSP in AD can predict the development of acute-on-chronic liver failure (ACLF)., Methods: Patients with AD were prospectively recruited at admission and underwent determination of PSP. In study part 1, we compared PSP in AD versus controls (stable decompensated and compensated cirrhosis). In study part 2, we prospectively followed patients with AD for 1 year and evaluated predictors of ACLF., Results: One hundred and seventy three patients with AD were included (median MELD: 18; CLIF-C AD score: 54). Compared with controls, patients with AD had higher levels of PSP (674 ng/L vs. 310 ng/L vs. 157 ng/L; p < 0.001). In patients with AD, Child-Pugh C and acute kidney injury were associated with higher levels of PSP. During the follow-up, 52 patients developed ACLF (median time from recruitment: 66 days). PSP, CLIF-C AD score, and Child-Pugh stage were independently associated with ACLF. A predictive model combining these variables (Padua model 2.0) accurately identified patients at higher risk of ACLF (AUROC 0.864; 95% CI 0.780-0.947; sensitivity 82.9%, specificity 76.7%). In patients at lower risk of ACLF based on a CLIF-C AD <50, a PSP >674 ng/L could discriminate between two groups at significantly different risk of ACLF. Finally, in patients who did not develop ACLF, baseline PSP was significantly higher in those who progressed toward unstable versus stable decompensated cirrhosis., Conclusion: The Padua model 2.0 can be used to identify patients with AD at high risk of ACLF. If these results are validated by external cohorts, PSP could become a new biomarker to improve risk stratification in AD., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background and Aims: Treatment of patients with acute on chronic liver failure (ACLF) admitted to the ICU is very limited. The aim of this pilot study was to evaluate the efficiency on liver function and safety of therapeutic plasma exchange (TPE) in critically ill cirrhotic patients admitted with ACLF in a liver ICU., Methods: This is a prospective cohort of patients with ACLF grade > 2 treated by TPE admitted to the ICU that was matched to a control group. TPE was performed using a plasma filter (TPE2000, BAXTER®) on a CRRT machine (Prismaflex®, Baxter®). Ratio and type of fluid replacement were 50 % with 5 % albumin solution followed by 50 % with fresh frozen plasma., Results: Seven patients with a mean age of 50.6 ± 7.8 years (all males) and 14 controls matched to age, sex, etiology and cause of decompensation were recruited. At ICU admission, mean MELD score was 39.1 ± 2.7, mean SOFA score was 11.6 ± 5.2 and mean CLIF SOFA score was 12.9 ± 2.6. The grade of ACLF was 3 for 3 patients (42.9 %) and 2 for 4 patients (57.1 %). The TPE group had significantly higher levels of bilirubin (392.3 ± 117.1μmol/l vs. 219 ± 185μmol/l , p = 0.04), and INR values (5.7 ± 3.4 vs. 3.5 ± 0.9, p < 0.005) compared to the control group. Patient survival was respectively 28.6 % and 14.3 % at 30 and 90 days in the TPE group and 35.7 % and 7.14 % in the control group respectively (HR: 1 (95 % CI 0.19- 5.2; p = 1). One patient in the TPE group had a liver transplantation 13 days after admission to ICU and is still alive and none in the control group. Two (28.6 %) patients died from complications related to the double lumen catheter used for TPE., Conclusion: This pilot study of TPE in patients with ACLF grade 2 and 3 showed a marked but transient improvement in liver function tests. TPE worth to be evaluated in large trials in ACLF patients, with a liver transplant project, and less organ failure., Competing Interests: Declaration of Competing Interest The authors whose names are listed certify that they have NO conflicts of interest to declare related to this manuscript., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: To evaluate the Chronic Liver Failure-Consortium Acute on Chronic Liver Failure score in acute on chronic liver failure patients admitted to ICUs from different global regions and compare discrimination ability with previously published scores.Design: Retrospective pooled analysis.Setting: Academic ICUs in Canada (Edmonton, Vancouver) and Europe (Paris, Barcelona, Chronic liver failure/Acute-on-Chronic Liver Failure in Cirrhosis [CANONIC] study).Patients: Sample of analysis of 867 cirrhotic patients with acute on chronic liver failure admitted to ICU. Cumulative incidence functions of death were estimated by acute on chronic liver failure grade at admission and at day 3. Survival discrimination abilities of Chronic Liver Failure-Consortium Acute on Chronic Liver Failure, Model for End-Stage Liver Disease, Acute Physiology and Chronic Health Evaluation II, and Child-Turcotte-Pugh scores were compared.Interventions: ICU admission for organ support.Measurements and Main Results: At admission 169 subjects (19%) had acute on chronic liver failure 1, 302 (35%) acute on chronic liver failure 2, and 396 (46%) had acute on chronic liver failure 3 with 90-mortality rates of 33%, 40%, and 74%, respectively (p < 0.001). At admission, Chronic Liver Failure-Consortium Acute on Chronic Liver Failure demonstrated superior discrimination at 90 days compared with Acute Physiology and Chronic Health Evaluation II (n = 532; concordance index 0.67 vs 0.62; p = 0.0027) and Child-Turcotte-Pugh (n = 666; 0.68 vs 0.64; p = 0.0035), but not Model for End-Stage Liver Disease (n = 845; 0.68 vs 0.67; p = 0.3). A Chronic Liver Failure-Consortium Acute on Chronic Liver Failure score greater than 70 at admission or on day 3 was associated with 90-day mortality rates of approximately 90%. Ninety-day mortality in grade 3 acute on chronic liver failure patients at admission who demonstrated improvement by day 3 was 40% (vs 79% in patients who did not).Conclusions: The Chronic Liver Failure-Consortium Acute on Chronic Liver Failure demonstrated better discrimination at day 28 and day 90 compared with Acute Physiology and Chronic Health Evaluation II and Child-Turcotte-Pugh. Patients who demonstrated clinical improvement post-ICU admission (e.g., acute on chronic liver failure 3 to 1 or 2) at day 3 had better outcomes than those who did not. In high-risk ICU patients (Chronic Liver Failure-Consortium Acute on Chronic Liver Failure > 70), decisions regarding transition to palliation should be explored between patient families and the ICU providers after a short trial of therapy. [ABSTRACT FROM AUTHOR]

Both the adaptive and innate arms of immunity are altered in patients with cirrhosis, which have both prognostic and clinical implications. Acute on chronic liver failure (ACLF), defined as decompensated cirrhosis with associated organ failure, carries a high risk of 28-day mortality and is marked by a significant inflammatory response. Patients with decompensated chronic liver disease display a shift from a chronic low-grade inflammatory state to one of intense inflammation, followed by the development of immunoparalysis. Considerable heterogeneity exists depending on the nature of the inciting cause and duration of ACLF. In this review, we will highlight the changes that immune cell populations in the liver undergo during decompensated liver disease, underscoring the immunological paradox between inflammation and increased susceptibility to infection that occurs during ACLF and progressive cirrhosis, as well as provide future perspectives regarding potentially useful biomarkers and possible avenues for treatment. [ABSTRACT FROM AUTHOR]

Liver failure can occur in patients with or without underlying chronic liver disease (mainly cirrhosis) and is, respectively, termed acute on chronic liver failure or acute liver failure (ALF). In both cases, it is associated with marked systemic inflammation and profound hemodynamic disturbances, that is, increased cardiac output, peripheral vasodilation, and decreased systemic vascular resistance, on top of several superimposed etiologies of shock. In patients with cirrhosis, sepsis is the main cause of intensive care unit admission but portal hypertension-related gastrointestinal hemorrhage is also common. Septic shock is also particularly frequent in patients with ALF and can complicate the initial hypovolemic shock related to poor oral intake, vomiting, and encephalopathy prior to admission. Given the susceptibility of the liver to hypoxia and also the potential deleterious effects of fluid on liver function, the assessment of hemodynamic status and volume responsiveness is especially important in these patients. However, one should keep in mind that the hyperdynamic state and low systemic vascular resistance in liver failure may bias the accuracy of some hemodynamic monitoring devices. Fluid therapy should use crystalloids, and balanced salt solutions may limit the risk of hyperchloremic acidosis and subsequent adverse kidney events. Nevertheless, the beneficial effects of albumin resuscitation have been demonstrated in patients with cirrhosis and may reflect more than mere volume expansion. [ABSTRACT FROM AUTHOR]

Cirrhosis represents the end stage of chronic liver disease and its transition from a compensated to a decompensated status is mainly driven by portal hypertension and systemic inflammation. Although relevant modifications in the evaluation of the coagulative balance in cirrhosis across its natural history have occurred and alterations in routine indices of hemostasis have lost their role as indicators of the hemorrhagic risk of patients with liver cirrhosis, these are still perceived as prone to bleed when admitted to invasive procedures. This view, which is still present in guidelines addressing the management of bleeding risk, makes preprocedural transfusion of plasma and platelets still an ongoing clinical practice. In this review, we describe the limitations of both bleeding risk assessment in cirrhotic patients admitted to radiologic and endoscopic invasive procedures and evaluate whether preventive strategies indicated by current guidelines can affect the procedure-related hemorrhagic events. [ABSTRACT FROM AUTHOR]

Aims We studied in-hospital predictors of mortality of acute on chronic liver failure (ACLF) in Indian patients. Methods Patients admitted to the intensive care unit of our institute fulfilling the definition of ACLF based on the Asia-Pacific Association for Study of Liver Disease (APASL) consensus were included. Complete history and medical evaluation to assess the etiology of underlying liver cirrhosis and to identify the acute precipitating insult of worsening liver function was done. Data was prospectively recorded and various scoring systems and individual clinical and laboratory parameters were assessed to identify predictors of 28 days mortality. Results 64 out of 240 patients screened for ACLF were analyszed in the study. Median age was 44 years and 53% were males. Alcohol was the primary cause of cirrhosis in 60.93%. Infections and active alcoholism was the main precipitating acute insult in 43% and 37% patients respectively. 28% patients had history of ingestion of hepato-toxic drugs as the acute insult. More than one acute insult was seen in 37.5% patients and type-II hepatic injury was the most common type. 28 days in hospital mortality was 43.75% and was highest in patients with sepsis (67.8%). Presence of hepato-renal syndrome and need for ventilation was associated with poor outcome. Though multiple variables were significant in predicting mortality on univariate analysis, yet on regression model only APACHE II and shock could significantly predict mortality with odds ratio of 3.18 and 9.14 respectively. Highest mortality was seen with cerebral and lung as organ failure and mortality increased as the number of organ failure worsened. CLIF-SOFA and APACHE-II scores having area under curve > 0.8 had higher ability to predict mortality Conclusion ACLF carries high short-term mortality and early intervention by liver transplantation should be considered in patients who shows high risk of mortality. [ABSTRACT FROM AUTHOR]

Introduction: ‘Acute-on-Chronic-Liver Failure (ACLF)’ entered hepatology practice by the end of the 20th century. Although we lack precise and universally agreed definitions, acute decompensation of chronic liver disease with jaundice and deranged clotting, multi-organ failure and high, short-term mortality are hallmarks of the syndrome. Timely recognition and and treatment, including urgent liver transplantation, may save the life of certain patients. The diagnosis and management are mostly based on clinical features, but some have suggested to incorporate histopathology (liver biopsy). This may add to the differentiation between acute and chronic disease, primary and concomitant etiologies, and identify prognostic determinants. Areas covered: A review of the literature on ACLF and the outcome of the discussions at a topical international meeting on specific histopathological aspects of diagnosis and prognosis of the syndrome. Expert commentary: There is a lack of standardized descriptions of histopathological features and there is limited prospective experience with the role of pathology of ACLF. It is important for the clinical hepatologist to understand the potential and limitations of (transjugular) liver biopsy in ACLF and for the pathologist to help address the clinical question and recognise the histopathological features that help to characterize ACLF, both in terms of diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: Cellulitis is a common infection in patients with cirrhosis but its impact on progression of liver disease has been hardly addressed. This study examines the incidence of acute kidney injury (AKI), predictive factors and its impacts on mortality in cirrhotic patients hospitalized for cellulitis. Methods: Retrospective data from cirrhotic patients hospitalized for cellulitis over the period January 2006 to September 2015 were analysed. AKI was defined according to revised criteria of the International Club of Ascites. Results: A total of 101 episodes of cellulitis were examined (70.3% men; mean age 60.6 ± 13.6 years). Of patients, 27% met criteria for acute on chronic liver failure (ACLF) (grade 1: 63%; grade 2: 22%; grade 3: 15%). AKI was recorded in 50.5% (type 1: 67%; type 2: 19%; type 3: 14%). AKI was present on admission in 21 of the 51 patients (41%) who developed it. In the remaining 30 patients (59%), AKI appeared during hospitalization and its development was associated with a MELD score >14 (70% vs 30%, P=.024). In‐hospital mortality was 10% and all patients who died had AKI. A high MELD score on admission, AKI and ACLF were associated with in‐hospital mortality (P<.05). One‐month transplant‐free survival was 84% (70% vs 98% in patients with and without AKI, P=.001). Conclusions: In cirrhotic patients, cellulitis is a serious infection that often leads to AKI and ACLF. AKI is a strong predictor of mortality in this setting. [ABSTRACT FROM AUTHOR]

• SPP1 mRNA was upregulated in PBMCs and hepatic CD45+ cells of ACLF patients. • SPP1 level was associated with organ failure and the severity of ACLF. • A higher SPP1 level in ACLF patients prior to LT indicated a poor outcome. • SPP1 enhanced the predictive capacities of existing models for post-LT prognosis. Acute on chronic liver failure (ACLF) is characterized by systemic inflammation and significant mortality, calling for accurate assessment due to the diverse prognosis of liver transplantation (LT). 8 patients with ACLF and 4 normal controls (NC) underwent peripheral blood mononuclear cells (PBMCs) transcriptomics, whereas 9 patients with ACLF and 3 NC had hepatic CD45+ T cells transcriptomics. The candidate indicator found in the transcriptomics was confirmed by a retrospective cohort (n = 137) and one prospective cohort (n = 68). Transcriptomics revealed significant differentially expression genes (DEGs) and bioprocesses related to the PBMCs and hepatic CD45+ T cells. Secreted phosphoprotein 1 (SPP1) was identified as a potential indicator for ACLF patients receiving LT, which was supported by evidence from the cross-sectional cohorts. As the condition of ACLF got worse, so did SPP1 levels, which were associated with liver failure and coagulation failure. SPP1 levels prior to LT were considerably greater in non-survivors of ACLF within 90 days than that in survivors. In the derivation cohort and validation cohort, ACLF patients with elevated SPP1 levels had significantly shorter cumulative survival durations than those with low SPP1 levels, P = 0.02 and P < 0.001, respectively. The SPP1-MELD and SPP1-chronic liver failure consortium (CLIF-C) ACLF scores had comparatively larger areas under the receiver operating characteristic curves (AUCs) than MELD (P = 0.0388) and CLIF-C ACLF (P = 0.045). The circulating SPP1 showed promise as a predictor for ACLF patients receiving LT, which demonstrated the need for tracking the clinical outcome of LT. [ABSTRACT FROM AUTHOR]

Aim. The aim of this study was to assess the effects of the molecular absorbent recirculating system (MARS) on patients with acute liver failure (ALF) and liver failure with cirrhosis (AoCLF) as well as in cholestatic patients with intractable pruritus in a Mexican population.Material and methods. From August 2003 to December 2011, MARS was used in 38 patients with ALF, 15 patients with AoCLF, and 17 cholestatic patients with intractable pruritus. The patients were examined using a standard liver function test and for vital signs, presence of ascites and encephalopathy before and after each treatment. The therapeutic response, patient status, follow-up status, and need for liver transplantation were determined.Results. Seventy-nine MARS procedures were performed. MARS was used for ALF in 54.3% of patients, AoCLF in 24.2%, and cholestatic disease in 21.5%. There were significant improvements in serum bilirubin (p = 0.000), aspartate aminotransferase (p = 0.000), alanine aminotransferase (p = 0.030), gamma-glytamyl transpeptidase (p = 0.044), alkaline phosphatase (p = 0.006), and encephalopathy grade (p = 0.000). Thirty-eight ALF patients were listed for emergency liver transplantation and treated with MARS; 20 of these patients died on a waiting list, 18 survived. only four underwent liver transplantation and 14 (37%) recovered without transplantation after the MARS procedure.Conclusion. MARS is a safe and effective procedure, especially for ALF patients. Our results suggest that MARS therapy can contribute to native liver recovery in ALF patients.