Pro-adrenomedullin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival

Abstract

Background and aim: Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failures, and high short-term mortality rates. In present study, we explored whether Pro-adrenomedullin (Pro-ADM), a biomarker of sepsis, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients.

Methods: 332 consecutive patients with AD of cirrhosis were prospectively enrolled. Pro-ADM was measured for all patients at baseline. Cox regression analysis was used to evaluate the impact of pro-ADM on short-term survival and developing ACLF during hospital stay.

Results: Serum pro-ADM levels were significantly high in non-survivors (p?<?.001) and showed significant correlation with ALT (r?=?0.181, p?=?.001), INR (r?=?0.144, p?=?.009), TB (r?=?0.368, p?<?.001), Creatinine (r?=?0.145, p?=?.004), MELD score (r?=?0.334, p =?<.001) and CLI-C OF score (r?=?0.375, p=?<.001). Serum pro-ADM at admission was shown to be a predictor of 28-day mortality independently of MELD and CLIF-C OF scores. Prognostic models incorporating pro-ADM achieved high C index for predicting 28-day mortality in AD patients of cirrhosis. Moreover, baseline pro-ADM was found to be predictive of ACLF development during hospital stay.

Conclusions: Serum pro-ADM levels correlate with multiorgan failure and are independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF.     

Acute-on-chronic liver failure: A comparison of three different diagnostic criteria

Introduction and aimDifferent criteria are applied for the diagnosis of acute-on-chronic liver failure (ACLF). Our aim was to compare the performance of different ACLF diagnostic criteria for predicting mortality.Materials and methodsThis was a prospective cohort study of adult cirrhotic patients admitted to a tertiary hospital for acute decompensation (AD) of cirrhosis. The evaluated outcome was mortality at 28 and 90 days, according to the different ACLF diagnostic criteria: Chronic Liver Failure Consortium (CLIF-C), Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC) and North American Consortium for the Study of End-Stage Liver Disease (NACSELD). Prognostic performance was evaluated using receiver operating characteristic (ROC) curves.Results146 patients were included. 43 (29.5%) with ACLF according to CLIF-C definition, 14 (9.6%) with ACLF by AARC definition, and 6 (4.1%) by NACSELD definition. According to Kaplan–Meier survival analyses median survival of patients with ACLF by CLIF-C definition was 27.0 days, median survival of patients with ACLF by AARC definition was 27.0 days, and median survival of patients with ACLF by NACSELD definition was 4.0 days. The areas under the ROC curves for performance evaluation in predicting mortality at 28 days for CLIF-C, AARC and NACSELD criteria were, respectively, 0.710, 0.560 and 0.561 (p = 0.002). Regarding 90-day mortality, the areas under the ROC curves were 0.760, 0.554 and 0.555 respectively (p < 0.001).ConclusionACLF definition proposed by CLIF-C had better performance in predicting mortality at 28 and 90 days when compared to criteria proposed by AARC and NACSELD.     

Chronic liver failure-consortium acute-on-chronic liver failure and acute decompensation scores predict mortality in Brazilian cirrhotic patients

AIM To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.METHODS This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium(CLIF-C) acute decompensation score(CLIF-C AD) and CLIF-C acute-on-chronic liver failure score(CLIF-C ACLF),regarding 28-d and 90-d mortality,as well as to compare them to other prognostic models,such as Model for End-Stage Liver Disease(MELD),MELD Sodium(MELD-Na),ChildPugh(CP) score,and the CLIF-C Organ Failure score(CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic(ROC) curves,area under the curves(AUC) and 95%CI.RESULTS One hundred and thirteen cirrhotic patients were included. At admission,18 patients had acute-onchronic liver failure(ACLF) and 95 individuals had acute decompensation(AD) without ACLF,of which 24 eventually developed ACLF during the course of hospitalization(AD evolving to ACLF group). The AD group had significantly lower 28-d(9.0%) and 90-d(18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group(both P 0.001). On the other hand,28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group(P = 0.542 and P = 0.708,respectively). Among patients with ACLF,at 28 d from the diagnosis,CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line,with an AUC(95%CI) of 0.71(95%CI: 0.54-0.88,P = 0.021). Among patients with AD,all prognostic scores performed significantly better than the reference line regarding 28-d mortality,presenting with similar AUCs: CLIF-C AD score 0.75(95%CI: 0.63-0.88),CP score 0.72(95%CI: 0.59-0.85),MELD score 0.75(95%CI: 0.61-0.90),MELD-Na score 0.76(95%CI: 0.61-0.90),and CLIF-C OF score 0.74(95%CI: 0.60-0.88). The same occurred concerning AUCs for 90-d mortality: CLIF-C AD score 0.70(95%CI: 0.57-0.82),CP score 0.73(95%CI: 0.62-0.84),MELD score 0.71(95%CI: 0.59-0.83),MELD-Na score 0.73(95%CI: 0.62-0.84),and CLIF-C OF score 0.65(95%CI: 0.52-0.78).CONCLUSION This study demonstrated that CLIF-C ACLF is the best available score for the prediction of 28-d mortality among patients with ACLF. CLIF-C AD score is also useful for the prediction of mortality among cirrhotic patients with AD not fulfilling diagnostic criteria for ACLF,but it was not superior to other well-established prognostic scores.     

The impact and evolution of acute-on-chronic liver failure in decompensated cirrhosis: A Portuguese single-center study

IntroductionAcute-on-chronic liver failure (ACLF) is a dynamic syndrome that should be assessed repeatedly. An algorithm for risk stratification in decompensated cirrhosis was recently proposed by the EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) Consortium.AimTo validate the EASL-CLIF Consortium scores in patients with and without ACLF.Materials and methodsRetrospective single-center cohort study including patients admitted for acute decompensation of cirrhosis between January 2014 and December 2015, and followed-up until December 2016. We separated patients with and without ACLF and compared the various EASL-CLIF Consortium scores to Child–Pugh and MELD for predicting 28-day (M28), 90-day and 12-month mortality. These scores were recalculated at different time points over 28 days.Results106 patients were included (age 60.3 ± 10.7 years; 87.7% male), 35.8% of whom met ACLF criteria on admission (50%) or during hospitalization. A CLIF-C AD Score ≥60 on admission was associated with a higher risk of developing ACLF. The onset of ACLF during hospitalization portended a poor prognosis. The prognostic performance of the CLIF-C ACLF Score (AUROC for M28: 0.856 ± 0.071) was globally comparable to that of Child–Pugh and MELD. Overall, ACLF resolved in 54.1% patients, resulting in increased survival. Almost 40% of the patients reached their final ACLF grade after ≥8 days, with 13.9% of ACLF patients experiencing resolution by then.DiscussionWe confirmed the accuracy and clinical value of the several proposed scores in our population. Prognosis was better defined by the early clinical course than by the initial evaluation, emphasizing the importance of repeated assessments.     

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.     

Comparison of the prognostic value of Chronic Liver Failure Consortium scores and traditional models for predicting mortality in patients with cirrhosis

Background and aim

Recently, the European Association for the Study of the Liver – Chronic Liver Failure (CLIF) Consortium defined two new prognostic scores, according to the presence or absence of acute-on-chronic liver failure (ACLF): the CLIF Consortium ACLF score (CLIF-C ACLFs) and the CLIF-C Acute Decompensation score (CLIF-C ADs). We sought to compare their accuracy in predicting 30- and 90-day mortality with some of the existing models: Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), MELD-Na, integrated MELD (iMELD), MELD to serum sodium ratio index (MESO), Refit MELD and Refit MELD-Na.

Hyperkalemia influences the outcome of patients with cirrhosis with acute decompensation (AD) and acute-on-chronic liver failure (ACLF)

IntroductionThe presence of hyperkalemia in different clinical scenarios has been described as a risk factor for mortality. Information about this electrolyte disorder in patients with cirrhosis is limited and there are no data in patients with acute-on-chronic liver failure (ACLF).AimThe aim of this study was to investigate whether hyperkalemia is a risk factor for mortality in patients with cirrhosis and acute decompensation (AD) with and without ACLF.MethodsWe performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,314 consecutive patients admitted to 29 European centers with AD both with and without associated ACLF (294 and 1020 respectively). Hyperkalemia was defined as serum potassium ≥ 5.0 mEq/L. All patients had at least one valid measure of serum potassium from admission and/or through the whole hospitalization.Results1314 patients were admitted with AD and 294 of them had ACLF at admission. Prevalence of hyperkalemia was significantly higher in ACLF versus AD (22.4% and 8.6% respectively, p<0.001). Hyperkalemia was associated with an increased 90, 180 and 360-day mortality risk in ACLF compared to AD (HR 10 vs 2.3 at 90-day p<0.001, 8.9 vs 3.1 at 180-day, p<0.001 and 5.8 vs 3.8 at 360-day, p<0.001). In a multivariate analysis, the presence of hyperkalemia during admission was independently associated with 90-day mortality [HR 2.4 (1.7 – 3.4)]. Variability of potassium between two valid measures ≥ 0.9 mg/dl was always also associated with a higher mortality rate. Addition of hyperkalemia to MELD score (MELD-K model) improved the accuracy to predict 90-day mortality risk.ConclusionsHyperkalemia is an independent risk factor of mortality in patients with AD and ACLF. Addition of hyperkalemia to the MELD score improves diagnostic accuracy to predict 90-day mortality in patients with AD and ACLF.     

Comparison of Dynamic Changes Among Various Prognostic Scores in Viral Hepatitis-Related Acute Liver Failure

Introduction and aim. Multiple prognostic scores are available for acute liver failure (ALF). Our objective was to compare the dynamicity of model for end stage liver disease (MELD), MELD-sodium, acute liver failure early dynamic model (ALFED), chronic liver failure (CLIF)-consortium ACLF score and King’s College Hospital Criteria (KCH) for predicting outcome in ALF.Materials and methods. All consecutive patients with ALF at a tertiary care centre in India were included. MELD, MELD-Na, ALFED, CLIF-C ACLF scores and KCH criteria were calculated at admission and day 3 of admission. Area under receiver operator characteristic curves (AUROC) were compared with DeLong method. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR) and diagnostic accuracy (DA) were reported.Results. Of the 115 patients included in the study, 73 (63.5%) died. The discrimination of mortality with baseline values of prognostic scores (MELD, MELD-Na, ALFED, CLIF-C ACLF and KCH) was modest (AUROC: 0.65-0.77). The AUROC increased on day 3 for all scores, except KCH criteria. On day 3 of admission, ALFED score had the highest AUROC 0.95, followed by CLIF-C ACLF 0.88, MELD 0.81, MELD-Na 0.77 and KCH 0.52. The AUROC for ALFED was significantly higher than MELD, MELD-Na and KCH (P < 0.001 for all) and CLIF-C ACLF (P = 0.05). ALFED score > 4 on day 3 had the best sensitivity (87.1%), specificity (89.5%), PPV (93.8%), NPV (79.1%), LR positive (8.3) and DA (87.9%) for predicting mortality.Conclusions. Dynamic assessment of prognostic scores better predicts outcome. ALFED model performs better than MELD, MELD, MELD-Na, CLIF-C ACLF scores and KCH criteria for predicting outcome in viral hepatitis-related ALF.     

Elevated neopterin levels are associated with acute-on-chronic liver failure and mortality in patients with liver cirrhosis

BackgroundMacrophage activation plays a central role in hepatic and systemic inflammation and is involved in the pathogenesis of acute-on-chronic liver failure (ACLF).AimsThis study aimed to investigate neopterin levels in patients admitted for acute decompensation (AD) of cirrhosis, evaluating its relationship with ACLF and prognosis.MethodsThis prospective cohort study included 205 adult subjects hospitalized for AD of cirrhosis. Twenty-one healthy subjects and 89 patients with stable cirrhosis were evaluated as controls.ResultsCirculating neopterin was higher in AD as compared to stable cirrhosis and healthy controls (p<0.001). ACLF was independently associated with higher neopterin levels (OR 1.015, 95% CI 1.002–1.028, p = 0.025). In the multivariate Cox regression analysis, neopterin levels (HR = 1.002, IC 95% 1.000–1.004, p = 0.041), Child–Pugh class C, and ACLF were predictors of 30-day survival. Among patients with ACLF, the Kaplan–Meier survival probability was 71.4% in those with neopterin levels < 25 nmol/L and 31.0% if neopterin ≥ 25 nmol/L (p<0.001).ConclusionsHigher circulating neopterin was associated with ACLF in patients hospitalized for AD of cirrhosis. Neopterin levels were also independently predictors of high short-term mortality, especially among patients with ACLF, and could represent a useful biomarker of macrophage activation in clinical practice.     

CLIF-C OFs在乙型肝炎相关慢性肝病急性失代偿患者中鉴别慢加急性肝功能衰竭的临床研究

目的探究欧洲肝病学会提出的适用于以酒精为病因引起的慢加急性肝衰竭诊断标准(CLIF Consortium Organ Failure score,CLIF-C OF)是否适用于乙型肝炎相关的慢加急性肝衰竭。方法筛选并纳入2005年1月至2010年12月上海瑞金医院乙型肝炎相关慢性肝病急性失代偿患者854例,按CLIF-C OF标准分为ACLF组和非ACLF组。分析ACLF组和非ACLF组的临床和实验室指标、病情严重程度和短期病死率。结果 ACLF组262例和非ACLF组592例。ACLF组较非ACLF组年龄大,肝、肾、脑、凝血、循环、呼吸功能衰竭情况均显著高于入院非ACLF组(P0.01),28 d和90 d病死率均显著升高(27.1%比3.1%、39.6%比4.9%,P0.01),提示病情更重。结论欧洲肝病学会所提出的评分标准可从乙型肝炎相关慢性肝病合并急性失代偿患者中筛选出一组病情更为危重、病死率更高的慢加急性肝衰竭患者群体。乙型肝炎相关慢性肝病并发急性失代偿患者中确实存在一群疾病程度更严重的ACLF群体,CLIF-C OF标准可将ACLF患者从乙型肝炎相关慢性肝病并发急性失代偿患者中区分出来,以指导临床医生治疗决策。     

Prognostic value of lectin pathway molecules and complement proteins in ascitic fluid and blood in patients with liver cirrhosis

Background and aim: Patients with liver cirrhosis and ascites have a poor prognosis with increased risk of infection related death, as advanced stages of cirrhosis are associated with immunodeficiency. We aimed to investigate immunologically active molecules in ascitic fluid and blood and their potential association to survival.

Materials and methods: In an exploratory pilot study; blood and ascitic fluid from 34 patients with liver cirrhosis of different etiology were analyzed for pattern recognition molecules (ficolin-1, ficolin-2, ficolin-3 and MBL) and complement proteins (C4 and C3). An observational follow-up study (minimum 17 months) was conducted to assess the association to all-cause mortality or liver transplantation.

Results: Ficolin-1, ficolin-2, MBL, C4 and C3 in ascitic fluid and ficolin-1, C4 and C3 in blood were significantly (p?=?.001–.027) lower in patients with Child-Pugh stage C (n?=?16, 47%) compared to Child-Pugh stage B cirrhosis (n?=?18, 53%). In multivariate COX-regression analysis low levels of ficolin-1(p?=?.036) and C3 (p?=?.025) in ascitic fluid and C4(p?=?.005) and C3 (p?=?.032) in serum were associated with all-cause mortality or liver transplantation independent of Child-Pugh score.

Conclusion: Levels of lectin-complement pathway molecules in ascitic fluid and blood are lower in patients with more advanced stage of cirrhosis. Low C4 and C3 in serum and C3 and ficolin-1 in ascitic fluid are risk factors for all-cause mortality or liver transplantation independently of liver function in patients with cirrhosis and ascites.     

Association of five-factor score with the mortality in Japanese patients with polyarteritis nodosa

Aim: To determine mortality and its predictive factors in Japanese patients with polyarteritis nodosa (PAN).

Methods: This retrospective single-center study determined the mortality of 18 patients with PAN who were admitted to Juntendo University Hospital from 1994 to 2016. The variables at baseline, including patient demographics, clinical characteristics, and treatment, were analyzed for their association with mortality.

Results: The median age of onset was 57.0 years. The 1-year survival rate was 100% (16/16) and the 5-year survival rate was 80.0% (8/10). The relationship between mortality, as defined by the survival rate and each variable was evaluated by Cox univariate analysis. A higher 2009 five-factor score (FFS) was associated with increased mortality, with a hazard ratio of 2.34 (p?=?.04). Analysis of the secondary outcome of relapse-free survival time revealed an association with rapid progressive renal failure, Birmingham Vasculitis Activity Score (BVAS), the 1996 FFS, and the 2009 FFS, with hazard ratios of 7.28 (p?=?.048), 1.26 (p?=?.02), 2.32 (p?=?.03), and 1.82 (p?=?.04), respectively.

Conclusion: We investigated mortality, relapse-free survival, and their predictive factors in Japanese patients with PAN. The BVAS and the 1996 FFS at diagnosis may be prognostic factors for relapse-free survival, and the 2009 FFS at diagnosis may be a prognostic factor for both mortality and relapse-free survival.     

Clinical characteristics of patients with liver cirrhosis and spontaneous portosystemic shunts detected by ultrasound in a tertiary care and transplantation centre

Abstract

Objectives: The clinical relevance of spontaneous portosystemic shunts detected by ultrasound is insufficiently investigated. The aim of this retrospective study was to assess the frequency and clinical relevance of spontaneous portosystemic shunts in patients with liver cirrhosis.

Methods: We evaluated portosystemic shunts, liver cirrhosis and spleen size by ultrasound in 982 patients with liver cirrhosis and correlated these with laboratory results, clinical data and the incidence of clinical endpoint deaths, liver transplantation and the development of HCC during the follow-up period (mean 1.26?±?1.53 years [range 0–7.2 years]).

Results: Portosystemic shunts were detected in 34% of the patients. These patients had a higher rate of alcohol-related cirrhosis (37% vs. 30%, p?=?.003), a higher MELD score (p?p?p?p?p?=?.041) and suffered more frequently from Child B/C stages (p?=?.03), hepatorenal syndrome (p?=?.03), massive ascites (p?=?.001) and spontaneous bacterial peritonitis (p?=?.011).

Conclusions: Patients with portosystemic shunts that are detected by ultrasound should be monitored carefully as these patients are associated with advanced liver disease and multiple clinical risk factors.     

Analysis of factors influencing survival in patients with severe acute pancreatitis

Objective: Acute pancreatitis (AP) ranges from a mild and self-limiting disease to a fulminant illness with significant morbidity and mortality. Severe acute pancreatitis (SAP) is defined as persistent organ failure lasting for 48?h. We aimed to determine the factors that predict survival and mortality in patients with SAP.

Methods: We reviewed a consecutive series of patients who were admitted with acute pancreatitis between January 2003 and January 2013. A total of 1213 cases involving 660 patients were evaluated, and 68 cases with SAP were selected for the study. Patients were graded based on the Computer Tomography Severity Index (CTSI), the bedside index for severity (BISAP), and Ranson’s criteria.

Results: The frequency of SAP was 5.6% (68/1213 cases). Among these patients, 17 died due to pancreatitis-induced causes. We compared several factors between the survivor (n?=?51) and non-survivor (n?=?17) groups. On multivariate analysis, there were significant differences in the incidence of diabetes mellitus (p?=?.04), Ranson score (p?=?.03), bacteremia (p?=?.05) and body mass index (BMI) (p?=?.02) between the survivor and non-survivor groups.

Conclusions: Bacteremia, high Ranson score, DM, and lower BMI were closely associated with mortality in patients with SAP. When patients with SAP show evidence of bacteremia or diabetes, aggressive treatment is necessary. For the prediction of disease mortality, the Ranson score might be a useful tool in SAP.     

Alcohol-related acute-on-chronic liver failure—Comparison of various prognostic scores in predicting outcome

Background and Aims

Various prognostic scores are available for predicting outcome in acute-on-chronic liver failure (ACLF). We compared the available prognostic models as predictors of outcome in alcohol-related ACLF patients.

Methods

All consecutive patients with alcohol-related ACLF were included. At admission, prognostic indices-acute physiology and chronic health evaluation score (APACHE II), model for end-stage liver disease (MELD), MELD-Na, Maddrey’s discriminant function (DF), age-bilirubin-INR-creatinine (ABIC), and Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C ACLF) score were calculated. Receiver operator characteristic (ROC) curves were plotted for all prognostic scores with in-hospital, 90-day, and 1-year mortality as outcome.

Results

Of the 171 patients, 170 were males, and grade 1 ACLF in 20 (11.7%), grade 2 in 52 (30.4%), and grade 3 in 99 (57.9%) patients. One hundred and nineteen (69.6%) died in-hospital. The median (IQR) Maddrey’s score, MELD, MELD-Na, ABIC, APACHE II, and CLIF-C ACLF were 87.8 (66.5–123.0), 33.1 (27.6–40.0), 34.4 (29.5–40.0), 8.5 (7.3–9.6), 15 (12–21), and 51.1 (44.1–56.4), respectively. On multivariate Cox regression analysis, independent predictors of in-hospital outcome were presence of hepatic encephalopathy (early HR, 2.078; 95%CI, 1.173–3.682, p?=?0.012 and advanced, HR, 2.330; 95% CI, 1.270–4.276, p?=?0.006), elevated serum creatinine (HR, 1.140; 95% CI, 1.023–1.270, p?=?0.018), and infection at admission (HR, 1.874; 95% CI, 1.160–23.029, p?=?0.010). On comparison of ROC curves, APACHE II and CLIF-C ACLF AUROC were significantly higher than MELD, MELD-Na, DF, and ABIC (p?<?0.05) for predicting in-hospital, 90-day, and 1-year mortality. The AUROC was highest for APACHE II followed by CLIF-C ACLF (Hanley and McNeil, p?=?0.660).

Conclusions

Alcohol-related ACLF has high in-hospital mortality. Among the available prognostic scores, CLIF-C ACLF and APACHE II perform best.

     

Serum keratin‐18 fragments as cell death biomarker in association with disease progression and prognosis in hepatitis B virus‐related cirrhosis

Extensive hepatocyte death leads to hepatic inflammation and contributes to systemic inflammation in decompensated cirrhosis. We aimed to investigate the prognostic value of serum cell death markers in patients with hepatitis B virus (HBV)‐related acute decompensation (AD) of cirrhosis with and without acute‐on‐chronic liver failure (ACLF). We studied two cohorts—cohort 1: 201 outpatients with stable chronic hepatitis B (49 cirrhosis); cohort 2: 232 inpatients with HBV‐related cirrhosis admitted for AD. Cell death was determined with serum keratin‐18 (K18) for total death and serum caspase‐cleaved‐K18 (cK18) for apoptosis. Survival analyses were performed using competing risk method. We found that serum K18 and cK18 were significantly (P < 0.001) higher in patients from cohort 2 than those from cohort 1. Among cohort 2, ACLF patients had significantly (P < 0.001) increased K18 and cK18 comparing to those without ACLF. Increased K18 and cK18 were mainly attributed to HBV flare and were associated with liver and coagulation failure. HBV‐AD patients without ACLF who admitted with upper tertile of K18 or cK18 were at higher risk of developing ACLF during follow‐up. Baseline serum K18 or cK18 was significantly associated with transplant‐free 90‐day survival independent of leucocytes, HBV DNA, bacterial infection, encephalopathy and severity scores. The combination of cell death biomarkers significantly improved the prognostic value of the currently established prognostic scores. The reduction of cell death level after standard treatment was associated with increased short‐term survival. In conclusion, measurements of serum K18 or cK18 in HBV decompensated cirrhosis are a promising tool for predicting ACLF and risk stratification of short‐term outcome.     

Acute pancreatitis in elderly patients: a single-center retrospective evaluation of clinical outcomes

Introduction: Acute pancreatitis (AP) incidence in the elderly population has increased in the last years. However, the role of age as influencing factor on the AP clinical course is still debated.

Methods: We reviewed clinical records of consecutive patients admitted with diagnosis of AP. Patients were divided in elderly (≥65 years) and non-elderly (<65 years). Primary endpoint was comparison of overall mortality. Secondary endpoint included ICU admission, in-hospital length of stay (LOS) and surgical procedures.

Results: We enrolled 352 elderly and 532 non-elderly patients. A higher mortality rate (7.4% vs 1.9%; p?<?.001), ICU admission rate (18.9% vs 6.3%; p?<?.001) and prolonged length of hospital stay (9 (6–14) vs 7 (5–11.7) days; p?=?.01) were registered in the ≥65 years group. Multivariate analysis identified age (OR: 3.5; 95% CI:1.645–7.555; p?=?.001), a higher Ranson score at admission (OR: 5.52; 95% CI:1.11–27.41; p<.001) and necrotic pancreatitis (OR: 8.6; 95% CI:2.46–30.27; p?=?.001) as independent predictors of mortality. Conversely age and necrotic pancreatitis were independent risk factors for higher LOS and ICU admission.

Conclusions: Patients with AP and age ≥65 years have a higher mortality, ICU admission and prolonged LOS. Early recognition and prompt treatment are key elements to improve outcomes in this population.     

Assessment of scoring systems for acute-on-chronic liver failure at predicting short-term mortality in patients with alcoholic hepatitis

AIMTo assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting short-term mortality among patients with alcoholic hepatitis.METHODSWe retrospectively collected data from 264 patients with clinically diagnosed alcoholic hepatitis from January to December 2013 at 21 academic hospitals in Korea. The performance for predicting short-term mortality was calculated for Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), CLIF Consortium Organ Failure score (CLIF-C OFs), Maddrey’s discriminant function (DF), age, bilirubin, international normalized ratio and creatinine score (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), model for end-stage liver disease (MELD), and MELD-Na.RESULTSOf 264 patients, 32 (12%) patients died within 28 d. The area under receiver operating characteristic curve of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86 (0.81-0.90), 0.89 (0.84-0.92), 0.79 (0.74-0.84), 0.78 (0.72-0.83), 0.81 (0.76-0.86), 0.83 (0.78-0.88), and 0.83 (0.78-0.88), respectively, for 28-d mortality. The performance of CLIF-SOFA had no statistically significant differences for 28-d mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality. A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d mortality.CONCLUSIONCLIF-SOFA and CLIF-C OF scores performed well, with comparable predictive ability for short-term mortality compared to the commonly used scoring systems in patients with alcoholic hepatitis.     

Evaluation of the criteria of hepatorenal syndrome type of acute kidney injury in patients with cirrhosis admitted to ICU

Introduction: Acute kidney injury (AKI) is a common and devastating complication in patients with cirrhosis. In 2015, the International Club of Ascites (ICA) proposed the definition of hepatorenal syndrome (HRS) type of AKI (HRS-AKI) in patients with cirrhosis. This study aims to evaluate the criteria of HRS-AKI in patients with cirrhosis admitted to ICU with regard to the prognosis.

Methods: A total of 349 cirrhotic patients consecutively admitted to intensive care unit (ICU) from 2010 to 2017 were retrospectively analyzed. Demographic parameters and clinical variables were collected with case report forms. The occurrence of AKI was determined according to ICA-AKI criteria. The phenotypes of AKI comprised pre-renal azotemia (PRA), acute tubular necrosis (ATN) and HRS. In our study, patients with PRA or ATN were classified to the non-HRS-AKI group.

Results: The incidence of AKI was 73.0%, comprising PRA (18.6%), ATN (16.3%) and HRS (38.1%). The overall hospital mortality was 64.5%. Patients with AKI had a significantly higher in-hospital (76.1%) and 180-d (86.7%) mortality. AKI type was an independent risk factor for in-hospital mortality by a multivariate logistic regression. The in-hospital and 180-d mortality rates were of no significant difference among patients with HRS-AKI stages 1–3.

Conclusions: AKI is common in patients with cirrhosis admitted to ICU, associated with significant in-hospital mortality. HRS-AKI was the most common and severe type of AKI in patients with cirrhosis admitted to ICU. The current staging system may not be applicable for HRS-AKI in patients with cirrhosis admitted to ICU.     

Pathological neutrophil migration predicts adverse outcomes in hospitalized patients with liver cirrhosis

Background and Aims

Given the early response of neutrophil granulocytes to infections, detection of pathological neutrophil migration might help in predicting adverse events in patients with liver cirrhosis.

Methods

Migration of blood neutrophils in hospitalized patients with cirrhosis was characterized by a novel standardized migration assay. Pathological neutrophil migration patterns were associated with a composite endpoint of ACLF, sepsis or death within 7 or 30 days.

Results

Overall, 125 patients were included, of whom 11 (8.8%) had compensated cirrhosis, 84 (67.2%) had acute decompensation (AD) and 30 (24%) had acute-on-chronic liver failure (ACLF). The migration response of neutrophils from patients with AD or ACLF to stimulation with the chemotactic formylpeptide f-Met-Leu-Phe (fMLP) was significantly impaired, while the response to chemokine (C-X-C motif)-ligand 8 (CXCL8) was affected less pronouncedly. In contrast, no relevant differences in response to CXCL1 were observed. Of note, neutrophils of a number of patients with AD and ACLF were largely immotile at resting and stimulated conditions. Patients with non-migrating neutrophils at unstimulated conditions were at high risk to develop the composite endpoint of ACLF, sepsis or death. Moreover, expression of chemokine receptors CXCR1 and CXCR2 was significantly decreased in patients with ACLF. Interestingly, the expression of chemokine receptors did not correlate with neutrophil migration patterns, but—based on the increased expression of the cell surface markers CD66b and CD177—neutrophils of patients with AD and ACLF were strongly pre-activated.

Conclusion

Pathological neutrophil migration in patients with cirrhosis indicates a high risk of developing adverse outcomes.