Acute Deterioration Of Liver Function Research Articles

Validation of MELD 3.0 in patients with alcoholic liver cirrhosis using prospective KACLiF cohort.

The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD-Na, in patients with alcoholic liver cirrhosis. This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD-Na, and MELD 3.0, for 30-day and 90-day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes. A total of 1096 patients were included in the study, with a mean age of 53.3±10.4years, and 82.0% were male. The mean scores for MELD, MELD-Na, and MELD 3.0 at the time of admission were 18.7±7.2, 20.6±7.7, and 21.0±7.8, respectively. At 30 and 90days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD-Na, and MELD 3.0 at 30days were 0.823, 0.820, and 0.828; and at 90days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90-day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels. MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant.

Transplantation for acute-on-chronic liver failure

Areview and discussion of the current literature on liver transplantation for acute-on-chronic liver failure (ACLF) was performed. The ACLF represents an acute deterioration of liver function with pre-existing liver disease and is associated with increasing multiorgan failure, depending on the stage. The 28-day mortality ranges to well over 70% in stage3 and requires rapid intensive medical treatment involving an interdisciplinary team experienced in transplantation medicine. Under optimized conditions, liver transplantation provides long-term survival rates comparable to other indications. Achieving this requires adifferentiated donor selection, choosing the appropriate time for transplantation in the context of adynamic disease course and the use of appropriate surgical techniques.

Assessment of liver transplant benefit and a novel strategy for liver donor allocation in acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is a type of complex clinical syndrome that is mainly characterized by acute deterioration of liver function based on chronic liver disease, hepatic and extrahepatic organ failures, and a high short-term mortality rate. The comprehensive medical treatment efficacy of ACLF is currently limited; thus, liver transplantation is the only viable potential treatment method. However, considering the severe liver donor shortage, economic and social costs, as well as the differences in disease severity and prognosis of different disease courses, it is particularly important to accurately assess the benefits of liver transplantation in patients with ACLF. Early identification and prediction, timing, prognosis, and survival benefits are discussed here by combining the latest research findings so as to optimize the liver transplantation treatment strategy for ACLF.

Acute-on-chronic liver failure: Terminology, mechanisms and management.

Acute-on-chronic liver failure is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. The pathogenesis involves extensive hepatic necrosis, which is associated with severe systemic inflammation and subsequently causes the cytokine storm, leading to portal hypertension, organ dysfunction, and organ failure. These patients have increased gut permeability, releasing lipopolysaccharide (LPS) and damage-associated molecular patterns (DAMPS) in the blood, leading to hyper-immune activation and the secretion of cytokines, followed by immune paralysis, causing the development of infections and organ failure in a proportion of patients. Early detection and the institution of treatment, especially in the "Golden Window" period of 7 days, gives an opportunity for reversal of the syndrome. Scores like the Asian Pacific Association for the Study of the Liver (APASL) ACLF research consortium (AARC) score, a model for end stage liver disease (MELD), and the CLIF Consortium acute-on-chronic liver failure (CLIF-C ACLF) score can help in the prediction of mortality. Treatment strategy includes treatment of acute insult. Patients should be considered for early transplant with MELD score >28, AARC score >10, high-grade hepatic encephalopathy, and in the absence of >2 organ failure or overt sepsis to improve survival of up to 80% at five years. Patients, with no option of transplant, can be treated with emerging therapies like faecal microbial transplant, plasma exchange, etc., which need further evaluation.

Prognostic study of acute-on-chronic liver failure patients: Usefulness of the fibrosis-4 index.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of liver function in cirrhotic patients. Since treatment of this condition is difficult, its prevention is of paramount importance. The predictors of ACLF are yet to be identified. To determine the prognosis of cirrhotic and ACLF patients, we conducted a retrospective study to analyze each parameter in ACLF patients. Cirrhotic patients with serum total-bilirubin level ≥5.0 mg/dL and prothrombin time (PT) value ≤40% after acute insults were diagnosed with ACLF, whereas patients who met one of the above criteria were diagnosed with extended type of ACLF (EX-ACLF). Overall, in this study, 18 ACLF and 16 EX-ACLF patients retrospectively investigated between 2008 and 2020, and each data was analyzed during and before acute insults. In the analysis during acute insults, renal and coagulation functions showed significant differences between the ACLF and EX-ACLF groups. Furthermore, the mortality rate in the ACLF group was higher than that in the EX-ACLF group. In the analysis before acute insults, aspartate aminotransferase (AST), Fibrosis-4 (FIB-4) index score, and AST to platelet ratio index (APRI) showed significant differences between the two groups. Among these, the FIB-4 index score correlated best with ACLF severity for identifying cirrhotic patients with poor prognosis. The FIB-4 index is the most useful predictor of ACLF severity. Careful management of cirrhotic patients with a high FIB-4 index score is considered beneficial to prevent ACLF occurrence.

Current Advances of Innate and Adaptive Immunity in Acute-on-Chronic Hepatitis B Liver Failure

Abstract Acute-on-chronic hepatitis B liver failure (ACHBLF) is a term used to define the acute deterioration of liver function that occurs in patients with chronic hepatitis B virus infection or hepatitis B virus-related liver cirrhosis. The specific pathogenesis of ACHBLF is still not completely understood. Current research has shown that an intense systemic inflammation is involved in the development of acute-on-chronic liver failure (ACLF). Meanwhile, a subsequent immune paresis over the course of ACLF favors the development of infection and sepsis. Deregulation in both the innate and adaptive immunity is the notable feature of ACLF. The dysregulated immune responses play a crucial role in disease progression and potentially drive organ failure and mortality in ACHBLF. In this review, we highlight the current knowledge of innate and adaptive immune cells in ACHBLF.

Acute-on-chronic liver failure: definition, diagnosis, and pathogenesis

Acute-on-chronic liver failure (ACLF) is a form of complex syndrome with acute deterioration of liver function that occurs on the basis of chronic liver disease, and is accompanied by hepatic and extrahepatic organ failure with high mortality rate. The short-term mortality rate of comprehensive internal medicine treatment is as high as 50%-90%. This paper summarizes the current common definitions and diagnostic criteria, early-warning prediction models, and pathogenesis of ACLF.

Hip Fractures in Patients With Liver Cirrhosis: Worsening Liver Function Is Associated with Increased Mortality.

Liver cirrhosis is associated with osteoporosis, imbalance leading to falls, and subsequent fragility fractures. Knowing the prognosis of patients with liver cirrhosis of varying severity at the time of hip fracture would help physicians determine the course of treatment in this complex patient popultaion. (1) Is there an association between liver cirrhosis of varying severity and mortality in patients with hip fractures? (2) Is there an association between liver cirrhosis of varying severity and the in-hospital, 30-day, and 90-day postoperative complications of symptomatic thromboembolism and infections including wound complications, pneumonia, and urinary tract infections? Between 2015 and 2019, we identified 128 patients with liver cirrhosis who were treated for hip fractures at one of two Level I trauma centers. Patients younger than 18 years, those with incomplete medical records, fractures other than hip fractures or periprosthetic hip fractures, noncirrhotic liver disease, status after liver transplantation, and metastatic cancer other than hepatocellular carcinoma were excluded. Based on these exclusions, 77% (99 of 128) of patients were eligible; loss to follow-up was 0% within 1 year and 4% (4 of 99) at 2 years. The median follow-up duration was 750 days (interquartile range 232 to 1000). Ninety-four patients were stratified based on Model for End-stage Liver Disease (MELD) score subgroup (MELD scores of 6-9 [MELD6-9], 10-19 [MELD10-19], and 20-40 [MELD20-40]), and 99 were stratified based on compensation or decompensation status, both measures for liver cirrhosis severity. MELD scores combine laboratory parameters related to liver disease and are used to predict cirrhosis-related mortality based on metabolic abnormalities. Decompensation, however, is the clinical finding of acute deterioration in liver function characterized by ascites, hepatic encephalopathy, and variceal hemorrhage, associated with increased mortality. MELD analyses excluded 5% (5 of 99) of patients due to missing laboratory values. Median age at the time of hip fracture was 69 years (IQR 62 to 78), and 55% (54 of 99) of patients were female. The primary outcome of mortality was determined at 90 days, 1 year, and 2 years after surgery. Secondary outcomes were symptomatic thromboembolism and infections, defined as any documented surgical wound complications, pneumonia, or urinary tract infections requiring treatment. These were determined by chart review at three timepoints: in-hospital and within 30 days or 90 days after discharge. The primary outcome was assessed using a Cox proportional hazard analysis for the MELD score and compensation or decompensation classifications; secondary outcomes were analyzed using the Fisher exact test. Patients in the MELD20-40 group had higher 90-day (hazard ratio 3.95 [95% CI 1.39 to 12.46]; p = 0.01), 1-year (HR 4.12 [95% CI 1.52 to 11.21]; p < 0.001), and 2-year (HR 3.65 [95% CI 1.68 to 7.93]; p < 0.001) mortality than those in the MELD6-9 group. Patients with decompensation had higher in-hospital (9% versus 0%; p = 0.04), 90-day (HR 3.35 [95% CI 1.10 to 10.25]; p = 0.03), 1-year (HR 4.39 [95% CI 2.02 to 9.54]; p < 0.001), and 2-year (HR 3.80 [95% CI 2.02 to 7.15]; p < 0.001) mortality than did patients with compensated disease. All in-hospital deaths were related to liver failure and within 30 days of surgery. The 1-year mortality was 55% for MELD20-40 and 53% for patients with decompensated disease, compared with 16% for patients with MELD6-9 and 15% for patients with compensated disease. In both the MELD and (de)compensation analyses, in-hospital and postdischarge 30-day symptomatic thromboembolic and infectious complications were not different among the groups (all p > 0.05). Ninety-day symptomatic thromboembolism was higher in the MELD20-40 group compared with the other two MELD classifications (13% for MELD20-40 and 0% for both MELD6-9 and MELD10-19; p = 0.02). The mortality of patients with preexisting liver cirrhosis who sustain a hip fracture is high, and it is associated with the degree of cirrhosis and decline in liver function, especially in those with signs of decompensation, defined as ascites, hepatic encephalopathy, and variceal hemmorrhage. Patients with mild-to-moderate cirrhosis (MELD score < 20) and those with compensated disease may undergo routine fracture treatment based on their prognosis. Those with severe (MELD score > 20) or decompensated liver cirrhosis should receive multidisciplinary, individualized treatment, with consideration given to palliative and nonsurgical treatment given their high risk of death within 1 year after surgery. Level III, therapeutic study.

Soluble urokinase plasminogen activator receptor is associated with short-term mortality and enhanced reactive oxygen species production in acute-on-chronic liver failure

BackgroundAcute-on-chronic liver failure (ACLF) is a comprehensive syndrome characterized by an acute deterioration of liver function and high short-term mortality rates in patients with chronic liver disease. Whether plasma soluble urokinase plasminogen activator receptor (suPAR) is a suitable biomarker for the prognosis of patients with ACLF remains unknown.MethodA prospective cohort of 282 patients with ACLF from three hospitals in China was included. 88.4% of the group was hepatitis B virus-related ACLF (HBV-related ACLF). Cox regression was used to assess the impact of plasma suPAR and other factors on 30- and 90-day mortality. Reactive oxygen species (ROS) production were detected to explore the role of suPAR in regulating neutrophil function in HBV-related ACLF.ResultThere was no difference in plasma suPAR levels between HBV-related and non-HBV-related ACLF. Patients with clinical complications had higher suPAR levels than those without these complications. A significant correlation was also found between suPAR and prognostic scores, infection indicators and inflammatory cytokines. Cox’s regression multivariate analysis identified suPAR ≥ 14.7 ng/mL as a predictor for both day 30 and 90 mortality (Area under the ROC curve: 0.751 and 0.742 respectively), independent of the MELD and SOFA scores in patients with ACLF. Moreover, we firstly discovered suPAR enhanced neutrophil ROS production under E.coli stimulation in patients with HBV-related ACLF.ConclusionssuPAR was a useful independent biomarker of short-term outcomes in patients with ACLF and might play a key role in the pathogenesis.Trial registration CNT, NCT02965560.

Role of tenofovir and telbivudine in treatment of hepatitis B related acute on chronic liver failure.

Introduction:ACLF is characterized by acute deterioration of liver function in patients with chronic liver disease. HBV is one of the most important causes of both acute insult and underlying chronic liver disease in ACLF. Reactivation of HBV is one of the common causes of ACLF in our region. ACLF requires multiple organ support and is associated with high short and medium term mortality. This is the reason why early, rapid reduction of HBV DNA is essential in treating ACLF-B.Methods:Consecutive patients of ACLF-B due to spontaneous reactivation of HBV (ALT> 5xULN or >2 x baseline and HBV DNA >20,000 IU/ml) were randomized into tenofovir group (300mg/day) and telbivudine group (600mg/day) along with standard medical treatment. Clinical and laboratory parameters were evaluated at baseline, day-7, day-14, day-30 and day-90. HBV DNA was evaluated at baseline and after three months of therapy. Primary end point was survival or death at three months. Secondary end point was improvement of liver function assessed by Child-Turcotte Pugh score and MELD score at three months.Results:30 patients were enrolled in the study and 15 of them received tenofovir and 15 patients received telbivudine. Most of the baseline parameters showed no difference except serum AST and serum creatinine level that showed statistically significant difference between two groups. After antiviral therapy both groups showed significant clinical improvement along with CTP and MELD scores. However statistically significant improvement between tenofovir and telbivudine groups was only seen with MELD score. Survival rate was 80% in tenofovir group and 60% in telbivudine group, but this was not statistically significant. Low serum albumin at baseline was predictor of mortality.Conclusion:In patients of ACLF-B, antiviral therapy with both tenofovir and telbivudine improve liver function, but there is no statistically significant difference in survival between tenofovir and telbivudine.

Serum Metabolic Disturbances Associated with Acute-on-chronic Liver Failure in Patients with Underlying Alcoholic Liver Diseases: An Elaborative NMR-based Metabolomics Study.

Objectives:Acute-on-chronic liver failure (ACLF), which develops in patients with underlying alcoholic liver disease (ALD), is characterized by acute deterioration of liver function and organ failures are secondary to that. The clear understanding of metabolic pathways perturbed in ALD-ACLF patients can greatly decrease the mortality and morbidity of patients through predicting outcome, guiding treatment, and monitoring response to treatment. The purpose of this study was to investigate the metabolic disturbances associated with ACLF using nuclear magnetic resonance (NMR)-based serum metabolomics approach and further to assess if the serum metabolic alterations are affected by the severity of hepatic impairment.Materials and Methods:The serum-metabolic profiles of 40 ALD-ACLF patients were compared to those of 49 age and sex-matched normal-control (NC) subjects making composite use of both multivariate and univariate statistical tests.Results:Compared to NC, the sera of ACLF patients were characterized by significantly decreased serum levels of several amino acids (except methionine and tyrosine), lipid, and membrane metabolites suggesting a kind of nutritional deficiency and disturbed metabolic homeostasis in ACLF. Twelve serum metabolic entities (including BCAA, histidine, alanine, threonine, and glutamine) were found with AUROC (i.e., area under ROC curve) value >0.9 suggesting their potential in clinical diagnosis and surveillance.Conclusion:Overall, the study revealed important metabolic changes underlying the pathophysiology of ACLF and those related to disease progression would add value to standard clinical scores of severity to predict outcome and may serve as surrogate endpoints for evaluating treatment response.

Serum Clusterin: A Potential Marker for Assessing the Clinical Severity and Short-Term Prognosis of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Background Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by acute deterioration of liver function and high short-term mortality. Clusterin, with biological functions similar to small heat shock proteins, can protect cells from apoptosis induced by various stressors. The aim of this study was to detect the level of serum clusterin in hepatitis B virus- (HBV-) related ACLF and to assess the predictive value of clusterin for the short-term prognosis of HBV-ACLF. Methods We detected serum clusterin by ELISA in 108 HBV-ACLF patients, 63 HBV-non-ACLF patients, and 44 normal controls. Results Serum clusterin was markedly lower in HBV-ACLF patients (median, 51.09 μg/mL) than in HBV-non-ACLF patients (median, 188.56 μg/mL) and normal controls (median, 213.45 μg/mL; all P < 0.05). Nonsurviving HBV-ACLF patients who died within 90 days had much lower clusterin levels than did surviving patients, especially those who died within 28 days (nonsurvival group vs. survival group: 39.82 ± 19.34 vs. 72.26 ± 43.52, P < 0.001; survival time ≤ 28 vs. survival time > 28: median 28.39 vs. 43.22, P = 0.013). The results showed that for identifying HBV-ACLF, the sensitivity of clusterin (93.7%) was similar to the sensitivities of the international normalized ratio (INR; 94.4%) and total bilirubin (TBIL; 94.8%), but its specificity (90.7%) was higher than that of prothrombin activity (PTA; 65.8%) and TBIL (69.8%) and was similar to INR (88.9%). As the concentration of clusterin increased, the mortality of HBV-ACLF patients decreased significantly from 59.3% to 7.0%. Clusterin had better ability for predicting the prognosis of HBV-ACLF patients than did the model for end-stage liver disease (MELD) score and the chronic liver failure consortium (CLIF-C) ACLF score (MELD vs. clusterin: P = 0.012; CLIF-C ACLF vs. clusterin: P = 0.031). Conclusion Serum clusterin is a potential biomarker for HBV-ACLF which can be used to assess clinical severity and the short-term prognosis of patients with this disease and may help clinicians identify HBV-ACLF with greater specificity and improved prognostic accuracy than existing prognostic markers.

Liver Transplantation in Acute-on-chronic Liver Failure.

Liver transplantation (LT) has revolutionized outcomes for cirrhotic patients. Current liver allocation policies dictate patients with highest short-term mortality receive the highest priority, thus, several patients become increasingly ill on the waitlist. Given cirrhosis is a progressive disease, it can be complicated by the occurrence of acute-on-chronic liver failure (ACLF), a syndrome defined by an acute deterioration of liver function associated with extrahepatic organ failures requiring intensive care support and a high short-term mortality. Successfully bridging to transplant includes accurate prognostication and prioritization of ACLF patients awaiting LT, optimizing intensive care support pre-LT, and tailoring immunosuppressive and anti-infective therapies post-LT. Furthermore, predicting futility (too sick to undergo LT) in ACLF is challenging. In this review, we summarize the role of LT in ACLF specifically highlighting (a) current prognostic scores in ACLF, (b) critical care management of the ACLF patient awaiting LT, (c) donor issues to consider in transplant in ACLF, and (d) exploring of recent post-LT outcomes in ACLF and potential opportunities to improve outcomes including current care gaps and unmet research needs.

Serum Sphingosine-1-Phosphate Is Decreased in Patients With Acute-on-Chronic Liver Failure and Predicts Early Mortality.

Sphingosine‐1‐phosphate (S1P) regulates pathophysiological processes, including liver regeneration, vascular tone control, and immune response. In patients with liver cirrhosis, acute deterioration of liver function is associated with high mortality rates. The present study investigated whether serum S1P concentrations are associated with disease severity in patients with chronic liver disease from compensated cirrhosis (CC), acute decompensation (AD), or acute‐on‐chronic liver failure (ACLF). From August 2013 to October 2017, patients who were admitted to the University Hospital Frankfurt with CC, AD, or ACLF were enrolled in our cirrhosis cohort study. Tandem mass spectrometry was performed on serum samples of 127 patients to assess S1P concentration. Our study comprised 19 patients with CC, 55 with AD, and 51 with ACLF, aged 29 to 76 years. We observed a significant decrease of S1P according to advanced liver injury from CC and AD up to ACLF (P < 0.001). S1P levels further decreased with progression to ACLF grade 3 (P < 0.05), and S1P highly inversely correlated with the Model for End‐Stage Liver Disease score (r = −0.508; P < 0.001). In multivariate analysis, S1P remained an independent predictor of 7‐day mortality with high diagnostic accuracy (area under the curve, 0.874; P < 0.001). Conclusion: In patients with chronic liver disease, serum S1P levels dramatically decreased with advanced stages of liver disease and were predictive of early mortality. Because S1P is a potent regulator of endothelial integrity and immune response, low S1P levels may significantly influence progressive multiorgan failure. Our data justify further elucidation of the diagnostic and therapeutic role of S1P in ACLF.

P: 23 Prospective Study on Mortality of Acute on Chronic Liver Failure and Its Predictors

BACKGROUND: Acute on chronic liver failure (ACLF) is a well recognized entity, characterized by an acute liver insult in patients with underlying chronic liver disease leading to sudden deterioration of liver function and a high mortality. We aimed to determine hospital, 28 days and 12 weeks mortality of ACLF, its predictors and precipitating factors METHODS: We conducted a prospective descriptive study at AIMS (Asian institute of medical sciences, Hyderabad, Pak.) from January 2018 to December 2018. We enrolled patients of ACLF as defined by Asian Pacific Association for the Study of Liver (APASL, 2014) and collected data to determine cause, precipitating acute insult, organ failure, ACLF grade MELD, and CTP scores. Patients were followed to determine hospital, 28 days and 12 weeks mortality and its predictors. RESULTS: Total patients were 117 with mean age of 40.9 +- 13.9 years (range 12–85). Majority were males 86 (73.5%) and 31 (26.5%) were females. Majority of patients 55 (47%) were Hepatitis B Virus (HBV) positive, among them 24 (43.6%) were with HDV co-infection. The most common precipitating acute insult was SEPSIS 65 (55.6). Others were drug induce liver injury (DILI) 8 (6.8%), HEV acute hepatitis 7 (5.9), HDV superinfection 5 (4.3%), HBV flair 4 (3.4%), alcohol binge drinking 4 (3.4%), surgery 2 (1.7%), acute PVT 2 (1.7%), Upper GI Bleed 1 (0.9%) and 20 (17.1%) were unknown. Hospital mortality was 49 (41.9%), 28 days 71 (60.7%) and 12 weeks mortality was 103 (88.0%). Organ failure (P = 0.002), ACLF grade (P = 0.002), encephalopathy (P = 0.001), MELD (P = 0.01) and AKI (P = 0.02) were found to be predictors of mortality. CONCLUSIONS: Acute-on-chronic liver failure (ACLF) is an acute deterioration of liver function superimposed on Chronic Liver Disease with a high mortality. In our study HBV infection was the commonest cuase of CLD, and sepsis was the commonest acute insult. We found high hospital, 28 days and 12 weeks mortality. Organ failure, ACLF grade, encephalopathy, MELD score and AKI were found to be predictors of mortality of ACLF.

Predictive factors for 28-day mortality in acute-on-chronic liver failure patients admitted to the intensive care unit

BackgroundAcute-on-chronic liver failure (ACLF) is an entity comprising an acute deterioration of liver function in cirrhotic patients, associated with organ failure(s) and high short-term mortality. We aimed to identify predictive factors for short-term mortality in patients admitted with ACLF that may benefit most from liver transplantation. MethodsRetrospective analysis of patients admitted in ACLF to a tertiary intensive care unit between 2013 and 2017 was performed. The EASL-CLIF acute-on-chronic liver failure in cirrhosis (CANONIC) criteria were used to define ACLF grade. Multivariable analysis using 28-day mortality as an end-point was performed, including severity-of-disease scores and clinical parameters. ResultsSeventy-seven patients were admitted in ACLF over the study period. The commonest aetiology of liver disease was alcohol related 52/77(68%) and the commonest precipitant of ACLF was variceal haemorrhage 38/77(49%). Overall 28-day mortality was 42/77(55%) [ACLF-(grade)1:3/42(7%); ACLF-2:10/42(24%); and, ACLF-3:29/42(69%);p = 0.002]. On multivariable analysis MELD ≥ 26 [odds ratio(OR) = 11.559; 95% confidence interval(CI):2.820–47.382;p = 0.001], ACLF-3 (OR = 3.287; 95%CI:1.047–10.325;p = 0.042) at admission and requirement for renal replacement therapy (OR = 5.348; 95%CI:1.385–20.645;p = 0.015) were independently associated with 28-day mortality. ConclusionPatients admitted with ACLF to intensive care have a high mortality rate. Defined early thresholds at admission can identify patients at the highest risk that may benefit most from liver transplantation.

The Role of the CLIF-C OF and the 2016 MELD in Prognosis of Cirrhosis with and without Acute-on-Chronic Liver Failure

Introduction and aim. Acute-on-chronic liver failure (ACLF) is defined by the development of acute deterioration of liver function associated with failure of other organs and high short-term mortality in patients with chronic liver disease (CLD). There is no consensus on the diagnostic criteria, and its independence from ordinary decompensation of CLD has frequently been questioned. This study aimed to identify and characterize this condition and to test the CLIF-C OF score comparing it to the 2016-MELD (with sodium) and the Child-Pugh.Material and methods. 18-month prospective observational study with systematic inclusion of admitted patients with CLD decompensation.Results. 39 patients had ACLF (33.1%). These patients experienced higher 28-day and 90-day mortality, when compared to patients without ACLF (43.6% and 64.1% vs. 2.5% and 7.6% respectively, p < 0.0001). ACLF was linked with a higher acute infection rate (74.4%). For all patients (N = 118), the scores 2016-MELD, CLIF-C OF and Child-Pugh showed an area under the curve (AUC) for 28-day mortality of 0.908, 0.844, 0.753 and for 90-day of 0.902, 0.814, 0.724 respectively, p < 0.0001 for all scores. The 90-day mortality 2016-MELD AUC was greater than the CLIF-C OF AUC, p = 0.021. Within ACLF patients, the 2016-MELD, CLIF-C ACLF and Child-Pugh scores showed an AUC of 0.774, 0.734, 0.584 (28-day) and 0.880, 0.771, 0.603 (90-day); for 2016-MELD p = 0.004 (28-day) and p < 0.0001 (90-day).Conclusion. ACLF is a frequent and relevant condition, associated with high mortality. The CLIF-C OF score revealed good accuracy and diagnoses ACLF when it is present. However, the 2016-MELD performed better for 90-day mortality prediction.

Glucocorticoid Regulates NLRP3 in Acute-On-Chronic Hepatitis B Liver Failure.

Acute-on-chronic hepatitis B liver failure (ACHBLF) refers to the acute deterioration of liver function during chronic hepatitis B virus infection, and is associated with high mortality, with rapid progression to death. Nucleotide-binding oligomerisation domain-like receptors (NLRs) Family Pyrin Domain Containing 3(NLRP3) inflammasome contributed to the pathogenesis of D-galactosamine and lipopolysaccharide-induced acute liver failure. However, the profile of NLRP3 in patients with ACHBLF has not been demonstrated. This study was therefore conducted to investigate the expression of NLRP3 in patients with ACHBLF and identify the effect of glucocorticoid on NLRP3. We recruited 70 patients with ACHBLF undergoing glucocorticoid treatment for 28 days, 30 patients with chronic hepatitis B (CHB), and 24 healthy controls (HCs) in this study. The relative messenger RNA (mRNA) level of NLRP3 and related genes were measured by reverse transcription polymerase chain reaction, the plasma levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. The mRNA level of NLRP3 was significantly higher in patients with ACHBLF than in patients with CHB as well as HCs (P<0.05). The plasma levels of IL-1β and IL-18 in patients with ACHBLF were significantly higher than in patients with CHB and HCs (P<0.05). The relative mRNA level of NLRP3 in surviving patients decreased significantly compared with that in patients who did not survive after glucocorticoid treatment (P<0.05). In conclusion, NLRP3 increased in patients with ACHBLF. Glucocorticoid could downregulate the expression of NLRP3 in surviving patients with ACHBLF.

Successful Pharmacotherapy for Multiple Acute Decompensation Events in a Cirrhotic Patient with Acute-on-chronic Liver Failure: A Case Report.

Acute-on-chronic liver failure (ACLF) is a potentially lethal syndrome, which is characterized by an acute deterioration of liver function in patients with chronic liver diseases. The present paper reported that an alcoholic cirrhotic patient with ACLF developed septic shock, hydrothorax, ascites, hepatic encephalopathy, acute kidney injury, and acute upper gastrointestinal bleeding at the same hospitalization and was successfully rescued by pharmacotherapy alone without any invasive intervention.

Liver transplantation for critically ill cirrhotic patients: Overview and pragmatic proposals.

Liver transplantation for critically ill cirrhotic patients with acute deterioration of liver function associated with extrahepatic organ failures is controversial. While transplantation has been shown to be beneficial on an individual basis, the potentially poorer post-transplant outcome of these patients taken as a group can be held as an argument against allocating livers to them. Although this issue concerns only a minority of liver transplants, it calls into question the very heart of the allocation paradigms in place. Indeed, most allocation algorithms have been centered on prioritizing the sickest patients by using the model for end-stage liver disease score. This has led to allocating increasing numbers of livers to increasingly critically ill patients without setting objective or consensual limits on how sick patients can be when they receive an organ. Today, finding robust criteria to deem certain cirrhotic patients too sick to be transplanted seems urgent in order to ensure the fairness of our organ allocation protocols. This review starts by fleshing out the argument that finding such criteria is essential. It examines five types of difficulties that have hindered the progress of recent literature on this issue and identifies various strategies that could be followed to move forward on this topic, taking into account the recent discussion on acute on chronic liver failure. We move on to review the literature along four axes that could guide clinicians in their decision-making process regarding transplantation of critically ill cirrhotic patients.