Platelet-to-white blood cell ratio: A novel and promising prognostic marker for HBV-associated decompensated cirrhosis

AimThe present study aimed to investigate associations of the platelet‐to‐white blood cell ratio (PWR)—a novel hematological indicator of inflammatory responses—with 30‐day outcomes in patients with HBV‐associated decompensated cirrhosis (HBV‐DeCi).MethodsWe recruited 131 patients with HBV‐DeCi for this retrospective study and extracted baseline clinical data and laboratory characteristics from medical records. Univariate and multivariate analyses were performed to determine major factors influencing 30‐day mortality. Area under the receiver operating characteristic curve analyses was performed to compare the predictive values of prognostic markers.ResultsDuring the 30‐day follow‐up period, 15 patients died. The PWR was significantly different between nonsurvivors and survivors. Lower PWR was found to be associated with an increased risk of mortality, and PWR was found to be an independent predictor of mortality in patients with HBV‐DeCi.ConclusionsOur results demonstrate that low PWR may be a predictor of poor prognosis in patients with HBV‐DeCi, and this factor may be a useful supplement to standard approaches to enable effective management of these patients.     

Lower level of IL‐28A as a predictive index of the artificial liver support system in effective treatment of patients with HBV‐ACLF

BackgroundHBV‐related acute‐on‐chronic liver failure (HBV‐ACLF) is the most common type of liver failure with high mortality. Artificial liver support system (ALSS) is an important mean to reduce the mortality of HBV‐ACLF but lacking index to assess its effectiveness. The cytokines are closely related to the prognosis of HBV‐ACLF patients with ALSS treatment, however, which is not fully understood.MethodsOne hundred forty‐two patients with HBV‐ACLF and 25 healthy donors were enrolled. The cytokine profile of peripheral blood was determined in the patients before and after ALSS treatment, and their relationship with effectiveness of ALSS treatment in HBV‐ACLF was analyzed.ResultsSerum IL‐28A levels were markedly lower in ALSS‐effective patients than those in non‐effective patients pre‐ALSS treatment. Similarly, serum IL‐6 was significantly lower in ALSS‐effective patients. Furthermore, for patients with effective treatment, serum IL‐28A levels were positively related with IL‐6 levels post‐ALSS (r = 0.2413, p = 0.0383). The ROC curve analysis showed that serum levels of IL‐28A (AUC = 0.6959 when alone or 0.8795 when combined with total bilirubin, platelet count and INR, both p < 0.0001) and IL‐6 (AUC = 0.6704, p = 0.0005) were useful indices for separating effective from non‐effective ALSS treatment of HBV‐ACLF patients. Multivariate logistic regression analysis demonstrated that lower level of IL‐28A was independently associated with higher effective rate of ALSS treatments.ConclusionsLower level of IL‐28A is a predictive biomarker for ALSS in effective treatment of HBV‐ACLF patients and IL‐28A may be potential target for the treatment of HBV‐ACLF.     

Characteristics and outcomes of critically ill patients with severe hyperammonemia

PurposeTo determine the etiology and outcomes of critically ill patients with severe hyperammonemia.Materials and methodsRetrospective observational study of adults (18 years or older) admitted to a MICU from 2007 to 2016 who had a serum ammonia level >180 μmol/L (3 times the upper limit of normal).ResultsThe 78 patients (45 male, 32 female) had a median age of 52 (interquartile range [IQR] 46–58) years. Hyperammonemia occurred most often with acute-on-chronic liver failure (ACLF) (49 %) or decompensated cirrhosis (27 %) and less often as a consequence of prior gastric bypass (9%), acute hepatic failure (6%), or valproic acid (3%). Median serum ammonia level was 201 μmol/L (IQR 126–265, range 18–736) on admission, with peak value of 245 μmol/L (IQR 205–336, range 185–842). Fifty (64%) patients died during the hospitalization. Cerebral edema was documented in 8 (10%) patients, only one of whom survived. Six of the 8 patients with cerebral edema had hyperammonemia related to ACLF, giving an incidence of 14% in this subset of patients. Neither mortality nor cerebral edema was associated with peak ammonia level.ConclusionsCritically ill patients with severe hyperammonemia have a high mortality rate and are at risk of developing cerebral edema.     

Prognostic factors and treatment effect of standard-volume plasma exchange for acute and acute-on-chronic liver failure: A single-center retrospective study

Patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have a high risk of mortality. Few studies have reported prognostic factors for patients receiving plasma exchange (PE) for liver support. We conducted a retrospective analysis using data of 55 patients with severe ACLF (n?=?45) and ALF (n?=?10) who received standard-volume PE (1–1.5 plasma volume) in the ICU. Hepatitis B virus infection accounts for the majority of ACLF (87%) and ALF (50%) patients. PE significantly improved the levels of total bilirubin, prothrombin time and liver enzymes (P<0.05). Thirteen ACLF patients (29%) and one ALF patient (10%) underwent liver transplantation. Two ALF patients (20%) recovered spontaneously without transplantation. The overall in-hospital survival rates for ACLF and ALF patients were 24% and 30%, and the transplant-free survival rates were 0% and 20%, respectively. For the 14 transplanted patients, the one-year survival rate was 86%. Multivariate analysis showed that pre-PE hemoglobin (P?=?0.008), post-PE hemoglobin (P?=?0.039), and post-PE CLIF-C ACLF scores (P?=?0.061) were independent predictors of survival in ACLF. The post-PE CLIF-C ACLF scores ≥59 were a discriminator predicting the in-hospital mortality (area under the curve?=?0.719, P?=?0.030). Cumulative survival rates differed significantly between patients with CLIF-C ACLF scores ≤ 58 and those with CLIF-C ACLF scores ≥ 59 after PE (P< 0.05). The findings suggest that PE is mainly a bridge for liver transplantation and spontaneous recovery is exceptional even in patients treated with PE. A higher improvement in the post-PE CLIF-C ACLF score is associated with a superior in-hospital survival rate.     

Relationship between tumor necrosis factor‐alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure

BACKGROUND. We have recently demonstrated that in humans, circulating levels of tumor necrosis factor‐α (TNF) correlate positively with severity of hepatic encephalopathy (HE) due to chronic liver failure.

AIM. The main aim of this larger population study is to determine the relationship between TNF and ammonia in patients with HE and chronic liver failure due to liver cirrhosis.

METHODS. Circulating levels of TNF and ammonia were measured in 108 patients with liver cirrhosis due to various etiologies in various clinical grades of HE (grades 0–4). TNF concentrations were measured in venous serum using commercially available solid‐phase high sensitivity enzyme‐linked immunosorbent assay. Ammonia levels were determined in venous plasma by the enzymatic method, using the glutamate dehydrogenase reaction.

RESULTS. The mean±SEM values of circulating levels of TNF and ammonia at presentation in patients with grade 0 of HE (n = 30) were 3.89±0.2?pg/mL and 49.8±2.8?µg/mL respectively, in patients with grade 1 of HE (n = 26) were 8.56±0.34?pg/mL and 101.6±6.5?µg/mL respectively, in patients with grade 2 of HE (n = 22) were 11.59±0.48?pg/mL and 160.3±10.7?µg/mL respectively, in patients with grade 3 of HE (n = 20) were 19.98±0.94?pg/mL and 228.8±16.1?µg/mL respectively, and in patients with grade 4 of HE (n = 10) were 51.53±8.59?pg/mL and 284.2±20.3?µg/mL respectively. A significant positive correlation was found between circulating levels of TNF and those of ammonia (r = 0.62, P<0.0001), and also between circulating levels of both substances and severity of HE in these patients (r = 0.95, P<0.0001, and r = 0.9, P<0.0001 respectively). TNF and ammonia were both significant independent predictors of severity of HE (P<0.0001 for both variables).

CONCLUSION. The results of this study demonstrate a significant relationship between TNF and ammonia in patients with chronic liver failure and HE, and so strengthen the suggestion that TNF could be strongly involved in the pathogenesis of HE in these patients. Hence, we suggest a new theory in the pathogenesis of HE, the ‘TNF theory’.     

Clinical impact of arterial ammonia levels in ICU patients with different liver diseases

Purpose

Increased arterial ammonia levels are associated with high mortality in patients with acute liver failure (ALF). Data on the prognostic impact of arterial ammonia is lacking in hypoxic hepatitis (HH) and scarce in critically ill patients with cirrhosis.

Methods

The patient cohort comprised 72 patients with HH, 43 patients with ALF, 100 patients with liver cirrhosis and 45 patients without evidence for liver disease. Arterial ammonia concentrations were assessed on a daily basis in all patients and the results were compared among these four patient groups and between 28-day survivors and 28-day non-survivors overall and in each group.

Results

Overall 28-day mortality rates in patients with HH, ALF and cirrhosis and in the control group were 54, 30, 49 and 27 %, respectively. Peak arterial ammonia levels differed significantly between transplant-free 28-day survivors and non-survivors in the HH and ALF groups (p < 0.01 for both). Multivariate regression identified peak arterial ammonia concentrations as an independent predictor of 28-day mortality or liver transplantation in patients with HH and ALF, respectively (p < 0.01). There was no association between mortality and arterial ammonia in patients with liver cirrhosis and in the control group. Admission arterial ammonia levels were independently linked to hepatic encephalopathy grades 3/4 in patients with HH (p < 0.01), ALF (p < 0.05) and cirrhosis (p < 0.05), respectively.

Conclusions

Elevated arterial ammonia levels indicate a poor prognosis in acute liver injury and are associated with advanced HE in HH, ALF and cirrhosis. Arterial ammonia levels provide additional information in the risk assessment of critically ill patients with liver disease.     

Relationship between tumor necrosis factor-alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure

BACKGROUND: We have recently demonstrated that in humans, circulating levels of tumor necrosis factor-alpha (TNF) correlate positively with severity of hepatic encephalopathy (HE) due to chronic liver failure.AIM. The main aim of this larger population study is to determine the relationship between TNF and ammonia in patients with HE and chronic liver failure due to liver cirrhosis. METHODS: Circulating levels of TNF and ammonia were measured in 108 patients with liver cirrhosis due to various etiologies in various clinical grades of HE (grades 0-4). TNF concentrations were measured in venous serum using commercially available solid-phase high sensitivity enzyme-linked immunosorbent assay. Ammonia levels were determined in venous plasma by the enzymatic method, using the glutamate dehydrogenase reaction. RESULTS: The mean+/-SEM values of circulating levels of TNF and ammonia at presentation in patients with grade 0 of HE (n = 30) were 3.89+/-0.2 pg/mL and 49.8+/-2.8 microg/mL respectively, in patients with grade 1 of HE (n = 26) were 8.56+/-0.34 pg/mL and 101.6+/-6.5 microg/mL respectively, in patients with grade 2 of HE (n = 22) were 11.59+/-0.48 pg/mL and 160.3+/-10.7 microg/mL respectively, in patients with grade 3 of HE (n = 20) were 19.98+/-0.94 pg/mL and 228.8+/-16.1 microg/mL respectively, and in patients with grade 4 of HE (n = 10) were 51.53+/-8.59 pg/mL and 284.2+/-20.3 microg/mL respectively. A significant positive correlation was found between circulating levels of TNF and those of ammonia (r = 0.62, P< 0.0001), and also between circulating levels of both substances and severity of HE in these patients (r = 0.95, P<0.0001, and r = 0.9, P<0.0001 respectively). TNF and ammonia were both significant independent predictors of severity of HE (P<0.0001 for both variables). CONCLUSION: The results of this study demonstrate a significant relationship between TNF and ammonia in patients with chronic liver failure and HE, and so strengthen the suggestion that TNF could be strongly involved in the pathogenesis of HE in these patients. Hence, we suggest a new theory in the pathogenesis of HE, the "TNF theory".     

Serum potassium levels and prognosis in HBV‐associated decompensated cirrhosis

BackgroundSerum potassium disorders are commonly seen in patients with advanced cirrhosis and have a detrimental effect on clinical outcome, but its role in HBV‐related decompensated cirrhosis (DeCi) is remained to be illustrated. We aim to assess the effects of serum potassium on outcomes in HBV‐DeCi patients.MethodsRetrospective study included 155 subjects. Multivariate analysis was used to determine the independent prognostic factor. Predictive ability of mortality for variables was determined using the receiver operating characteristics curves.ResultsThe 30‐day in‐hospital mortality was 12.9%. Serum potassium levels differed markedly between survivors and non‐survivors. On multivariate analysis, Model for End‐Stage Liver Disease (MELD) score and serum potassium level were identified as independent predictors of outcomes in HBV‐DeCi patients. The combination of serum potassium and MELD score could improve prognostic accuracy in these patients.ConclusionsOur findings suggest that serum potassium is an effective predictor for poor outcomes in HBV‐DeCi patients.     

New prognostic factor for hepatitis B virus‐related decompensated cirrhosis: Ratio of monocytes to HDL‐cholesterol

AimHepatitis B virus‐related decompensated cirrhosis (HBV‐DeCi) has a high mortality rate, and it remains a challenge to predict its outcomes in clinical practice. We aimed to determine the association between monocyte‐to‐HDL‐cholesterol ratio (MHR) and short‐term prognosis in HBV‐DeCi patients.MethodsA total of 145 HBV‐DeCi patients were enrolled. A multivariate analysis was performed to identify predictors of mortality. The findings were validated by a receiver operating characteristic analysis using the area under the curve (AUC).ResultsA total of 20 (13.8%) patients had died 30 days after admission. MHR was markedly increased in the non‐survivors compared with the survivors. In the multivariate analysis, MHR was identified as an independent risk factor for mortality, with a significant predictive value (AUC = 0.825; sensitivity, 90.0%; specificity, 62.4%).ConclusionsElevated MHR is associated with increased mortality rate in HBV‐DeCi patients.     

Pharmacokinetics/pharmacodynamics of L‐ornithine phenylacetate in overt hepatic encephalopathy and the effect of plasma ammonia concentration reduction on clinical outcomes

Hepatic encephalopathy (HE) is a serious neurocognitive complication of liver dysfunction, often associated with elevated plasma ammonia. Ornithine phenylacetate (OP), a potent ammonia scavenger, is being evaluated for the treatment of acute/overt HE. The pharmacokinetics and pharmacodynamics of OP in patients with HE were characterized in this phase IIb study ({"type":"clinical-trial","attrs":{"text":"NCT01966419","term_id":"NCT01966419"}}NCT01966419). Adult patients hospitalized with an overt HE episode, cirrhosis, and plasma ammonia above the upper limit of normal (ULN) who failed to improve after 48 hours’ standard care were randomly assigned to continuous intravenous OP (10, 15, or 20 g/day, based on Child–Turcotte–Pugh score) or matching placebo for 5 days. Plasma levels of ornithine and phenylacetic acid (PAA) and plasma/urinary levels of phenylacetylglutamine (PAGN) (primary metabolite of PAA) were regularly assessed; plasma ammonia level was the primary pharmacodynamic variable. PAA demonstrated dose‐dependent pharmacokinetics; ornithine and PAGN levels increased with dose. PAGN urinary excretion represented ~50%–60% of administered PAA across all doses. Mean reduction in plasma ammonia with OP at 3 hours postinfusion was significantly greater versus placebo (p = 0.014); and time to achieve plasma ammonia less than or equal to the ULN was significantly reduced (p = 0.028). Achievement of clinical response based on HE stage was associated with a greater reduction in mean plasma ammonia level (p = 0.009). OP effects on plasma ammonia were consistent with its proposed mechanism of action as a primary ammonia scavenger, with a significant association between reduced plasma ammonia and improvement in HE stage. OP should be further evaluated as a promising treatment for hyperammonemia in patients with overt HE.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Overt hepatic encephalopathy (OHE) is characterized by severe liver impairment and signs of neurocognitive dysfunction commonly associated with hyperammonemia. Ornithine phenylacetate (OP), a potent ammonia scavenger, has an acceptable safety profile in patients with decompensated cirrhosis and gastrointestinal bleeding, and lowers plasma ammonia levels.

• WHAT QUESTION DID THIS STUDY ADDRESS?

What are the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of OP and its metabolites in patients hospitalized due to OHE with cirrhosis and hyperammonemia?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

PK/PD analysis results are consistent with the putative mechanism of action of OP. Mean plasma levels of OP analytes reach steady state in approximately 48−72 hours, regardless of dose, and appear to increase as liver function declines. OP treatment significantly reduces plasma ammonia and improves clinical OHE stage, supporting the proposed central role of ammonia in HE.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

OP treatment may be beneficial as a first‐line treatment for patients with OHE; however, additional studies are warranted.     

Prognostic value of dynamic cardiac biomarkers in patients with acquired refractory thrombocytopenic purpura: A retrospective study in Chinese population

IntroductionThrombotic thrombocytopenic purpura (TTP) is becoming a curable disease with the introduction of therapeutic plasma exchange (TPE). However, cardiovascular complications remain essential causes of mortality in patients with refractory TTP, while the association of cardiac biomarkers with the prognosis of TTP warrants further investigation.MethodsPatients admitted to the First Affiliated Hospital of Soochow University for refractory TTP from 2013 through 2020 were included in this retrospective study. Clinical characteristics were collected from electronic health records. Biomarker levels on admission and post TPE were recorded. Logistic regression was adopted to identify risk factors for mortality.ResultsA total of 78 patients with refractory TTP were included in this study. Twenty‐one patients died during hospitalization, with a mortality rate of 26.9%. High‐sensitivity cardiac troponin T (hs‐cTnT), N‐terminal probrain natriuretic peptide (NT‐proBNP), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ratios (AAR) were increased in deceased patients compared with the survival group. Multivariate analysis showed that AAR after TPE was associated with overall mortality (OR: 4.45, 95% CI 1.09–18.19). The areas under the receiver operator characteristic curve (AUC) of AAR, hs‐cTnT, and NT‐proBNP for the association with mortality were 0.814, 0.840, and 0.829, respectively.ConclusionHigher post‐TPE cardiac biomarker levels are associated with increased in‐hospital mortality in patients with refractory TTP.     

Association between serum lactate dehydrogenase and 60‐day mortality in Chinese Hakka patients with acute myeloid leukemia: A cohort study

BackgroundThere is evidence that a high level of serum lactate dehydrogenase (LDH) is associated with poorer overall survival in acute myeloid leukemia (AML), but its link to 60‐day mortality of AML remains unclear.MethodsAll patients newly diagnosed with AML were included in this cohort study. LDH was measured for the first time after admission. Multivariable logistic regression was used to explore the association between serum LDH and 60‐day mortality. Interaction and stratified analyses were conducted including age, sex, albumin, glucose, myoglobin, and standard chemotherapy.ResultsThree hundred and seventy‐one patients ≥15 years of age, who were newly diagnosed with AML, were consecutively selected. The total prevalence of 60‐day mortality was 27.2% (101/371), while it was 32.1% (42/131) and higher than in the LDH ≥570U/L compared with the LDH<570U/L, with the prevalence of 24.6% (59/240); however, the difference was not statistically significant. In multivariate regression models, odd ratios and corresponding 95% confidence intervals (CIs) for Log₂ and twice limit of normal (ULN) of LDH were 1.46 (1.0, 2.14) and 2.76 (1.24, 6.16), respectively. Interaction analysis revealed no interactive role in the association between LDH concentration and 60‐day mortality.ConclusionsSerum LDH level was associated with 60‐day mortality, especially for the patients with LDH ≥570U/L.     

Hyponatremia influences the outcome of patients with acute-on-chronic liver failure: an analysis of the CANONIC study

Introduction

Hyponatremia is a marker of poor prognosis in patients with cirrhosis. This analysis aimed to assess if hyponatremia also has prognostic value in patients with acute-on-chronic liver failure (ACLF), a syndrome characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality.

Methods

We performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,341 consecutive patients admitted to 29 European centers with acute decompensation of cirrhosis (including ascites, gastrointestinal bleeding, hepatic encephalopathy, or bacterial infections, or any combination of these), both with and without associated ACLF (301 and 1,040 respectively).

Results

Of the 301 patients with ACLF, 24.3% had hyponatremia at inclusion compared to 12.3% of 1,040 patients without ACLF (P <0.001). Model for end-stage liver disease, Child-Pugh and chronic liver failure-SOFA scores were significantly higher in patients with ACLF and hyponatremia compared to those without hyponatremia. The presence of hyponatremia (at inclusion or during hospitalization) was a predictive factor of survival both in patients with and without ACLF. The presence of hyponatremia and ACLF was found to have an independent effect on 90-day survival after adjusting for the potential confounders. Hyponatremia in non-ACLF patients nearly doubled the risk (hazard ratio (HR) 1.81 (1.33 to 2.47)) of dying at 90 days. However, when considering patients with both factors (ACLF and hyponatremia) the relative risk of dying at 90 days was significantly higher (HR 6.85 (3.85 to 12.19) than for patients without both factors. Patients with hyponatremia and ACLF had a three-month transplant-free survival of only 35.8% compared to 58.7% in those with ACLF without hyponatremia (P <0.001).

Conclusions

The presence of hyponatremia is an independent predictive factor of survival in patients with ACLF. In cirrhosis, outcome of patients with ACLF is dependent on its association with hyponatremia.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0700-0) contains supplementary material, which is available to authorized users.     

红细胞分布宽度在慢加急性肝衰竭患者预后预测中的应用

目的 旨在探讨红细胞分布宽度（RDW）在慢加急性肝衰竭（ACLF）患者预测预后中的应用。方法 选取乙型肝炎病毒（HBV）相关性ACLF患者78例,根据预后分为生存及死亡组,检测患者外周血RDW水平及其他相关临床指标。结果 ACLF死亡患者外周血RDW水平高于生存患者（t=-3.568,P=0.004）。RDW与白细胞计数（WBC）、中性粒细胞绝对值/淋巴细胞绝对值（NLR）、总胆红素（TBIL）、终末期肝脏病评分（MELD）存在相关性（P值均<0.05）。受试者工作特征曲线（ROC）分析显示：RDW预测ACLF死亡率的ROC曲线下面积（AUC）为0.64,Cut off值为17.15%,灵敏度和特异度分别为54.2%和67.9%。多因素回归分析显示：RDW、NLR、国际标准化比值（INR）是ACLF患者短期死亡率的独立危险因素（OR值=1.444、1.305、1.891,P值均<0.05）,生存分析显示：RDW≥17.15%患者生存率低于RDW＜17.15%患者（P<0.05）。结论 外周血RDW是临床预测ACLF患者短期预后的简单、有效的指标。     

Low albumin levels are associated with mortality in the critically ill: A retrospective observational study in a multidisciplinary intensive care unit

Background Albumin is a determinant of plasma colloid oncotic pressure and buffering capacity. It is a carrier protein for drugs and is important for normal functioning of the glycocalyx. Hypoalbuminaemia is common in the critically ill and has been associated with adverse outcomes. The association between hypoalbuminaemia and outcome has not been specifically explored in the South African context. Objectives To determine whether albumin levels on admission and changes in albumin levels were associated with intensive care unit (ICU) mortality in a heterogenous critically ill population. Methods This was a retrospective observational study of 247 adult patients who were admitted to a multidisciplinary ICU. Albumin levels were measured on admission and 48 hours later, alongside other biochemical and clinical parameters to determine whether they were predictive of ICU mortality. Results The lowest level of albumin on admission was 8 g/L and the highest was 43 g/L. The incidence of hypoalbuminaemia (using the laboratory reference range) was 93.9% on admission and 99.4% at 48 hours. Receiver operating characteristic curve analysis provided an optimal albumin cut-off of 18.5 g/L. Using this cut-off, hypoalbuminaemia at admission and at 48 hours was associated with increased ICU mortality. Hypoalbuminaemia at admission was an independent predictor of mortality using multivariable analysis (OR 3.74; 95% confidence interval 1.87 - 4.48). Conclusion Hypoalbuminaemia is associated with increased ICU mortality. There is currently no evidence to support the use of albumin replacement therapy. Further research is required to determine its role in critically ill patients. Contributions of the study Hypoalbuminaemia is common in critically ill South African (SA) patients and is associated with increased ICU mortality. This has not been well explored in the SA setting. We found that an optimal albumin cut-off was 18.5 g/L, which was much lower than the limits of the laboratory reference range.     

Fatal cerebral edema in patients with decompensated cirrhosis: A case series

PurposeUnlike patients with acute liver failure, patients with cirrhosis are not traditionally thought to be at risk for developing cerebral edema. In the largest case series to date, we document clinical characteristics of cirrhotic patients who develop cerebral edema.Materials and methodsIn this retrospective case series, seventeen adult patients with acute-on-chronic liver failure (ACLF) were identified using Morbidity & Mortality data. Neurological decompensation was defined by focal neurological deficits or abnormal movements. Elevated ICP was diagnosed clinically by pupillary reflex change improving with hyperosmolar therapy, or by herniation on CT. Pulsatility indices >1.2 on transcranial Dopplers (TCDs) and/or optic nerve sheath diameter (ONSD) >0.5 cm were acceptable alternatives.ResultsMedian MELD-Na was 36 (IQR 31.5,43) compared with 20 (IQR 19,23) prior to admission. Neurological decompensation was associated with abnormal pupil reactivity in 76% and abnormal movements in 65%. Cerebral edema was diagnosed by CT (n = 14). For those too ill to transport, elevated ICP was confirmed with TCDs for three patients and ONSD for two. Mortality was 100% a median of 3 days (IQR 1.5,5) from neurologic decompensation.ConclusionsACLF patients with neurological decompensation exhibit distinct clinical changes. Noninvasive bedside techniques may serve as surrogate measures for ICP.     

Association of circulating long non‐coding RNA HULC expression with disease risk,inflammatory cytokines,biochemical index levels,severity‐assessed scores,and mortality of sepsis

BackgroundThe present study aimed to explore the correlation of long non‐coding RNA highly up‐regulating in liver cancer (lncRNA HULC) with disease risk, inflammatory cytokines, biochemical indexes, disease severity, infective features, and 28‐day mortality of sepsis.MethodsTotally 174 sepsis patients and 100 controls were enrolled. Peripheral blood samples were collected from sepsis patients after diagnosis and from controls at enrollment, respectively, and further for separation of peripheral blood mononuclear cell (PBMC) and serum samples. PBMC samples were for lncRNA HULC detection, and serum samples were for inflammatory cytokine detection.ResultsLncRNA HULC expression was increased in sepsis patients compared with controls. Moreover, lncRNA HULC was positively associated with TNF‐α, IL‐6, IL‐17, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, serum creatinine, white blood cell, and C‐reactive protein in sepsis patients, but not in controls. Furthermore, in sepsis patients, lncRNA HULC expression was positively correlated with acute physiology and chronic health evaluation II score and sequential organ failure assessment score, but not correlated with primary infection sites or primary infection organisms; meanwhile, lncRNA HULC expression was increased in deaths compared with survivors; subsequent receiver operating characteristic curve indicated that lncRNA HULC presented good value in predicting increased 28‐day mortality (AUC: 0.785, 95% CI: 0.713–0.857), and its independent predictive value for mortality was also verified by multivariate analysis.ConclusionLncRNA HULC is correlated with higher disease risk, severity, and inflammation and serves as an independent factor for predicting increased mortality, suggesting its potential in promoting accuracy of prognostic prediction for sepsis management.     

Low hemoglobin levels are associated with direct antiglobulin test positivity in patients with acute-on-chronic liver failure

BackgroundMultiple factors contribute to anemia in patients with Hepatitis B virus (HBV)related acute-on-chronic liver failure (ACLF); however, the mechanism is unclear. The purpose of this study was to evaluate the clinical significance of the direct antiglobulin test (DAT) in patients with HBV related ACLF.MethodsDAT was used to detect immunoglobulins and/or complement proteins on the surface of erythrocytes.ResultsWe recruited 78 HBV-associated ACLF patients, 30 chronic hepatitis B(CHB)patients and 40 healthy people between October 2015 and May 2016. In HBV related ACLF patients, the hemoglobin concentration, number of erythrocytes, and hematocrit value were significantly lower, while the erythrocyte distribution width was significantly higher, compared to patients with CHB and healthy controls (HCs) (P < 0.001). The rates of DAT positivity in HBV related ACLF patients, CHB patients, and HCs were 62.8 %, 13.3 %, and 0%, respectively. DAT-positive ACLF patients exhibited lower Hb levels, older average age, as well as higher total bilirubin, alanine aminotransferase, and complement component 3 levels compared to DAT-negative patients.ConclusionsHBV related ACLF patients showed significant alterations in erythrocyte parameters, possibly reflecting disease development and severity. The high presence of erythrocyte autoantibodies suggested that immunologic clearance of erythrocytes contributed to multifactorial anemia in HBV related ACLF patients.     

Serum Ammonia in Cirrhosis: Clinical Impact of Hyperammonemia,Utility of Testing,and National Testing Trends

PurposeAmmonia is central to the pathophysiology of hepatic encephalopathy (HE) in cirrhosis. Serum ammonia levels have prognostic value and have been implicated in sarcopenia, hepatotoxicity, and immune dysfunction. Studies indicate that clinicians frequently order serum ammonia levels in decompensated cirrhosis; however, the clinical utility of serum ammonia levels has been questioned, citing challenges in accurate measurement and interpretation. This article involves a primary review of the literature to evaluate the importance of serum ammonia in cirrhosis and examines the clinical utility of serum ammonia levels in the management of HE. In addition to the review, we conducted primary research using national claims data to investigate national trends in practitioner use of serum ammonia.MethodsWe identified all hospitalizations in a national commercial claims database with and without ammonia testing among adults with noncirrhotic chronic liver disease and cirrhosis from January 1, 2007, to September 31, 2015. We calculated the proportion of hospitalizations with ammonia testing and the number of ammonia tests per 1000 hospital-days.FindingsProportion of hospitalizations with ammonia testing and ammonia tests per 1000 inpatient-days increased significantly from 2007 to 2015, and particularly in 2014 and 2015, for all groups.ImplicationsA review of the literature indicated that elevated serum ammonia contributes to neurotoxicity, sarcopenia, and immune dysfunction in cirrhosis. However, serum ammonia testing has not had consistent benefit in clinical diagnosis or management of HE in cirrhosis. Claims data indicated that ammonia testing increased substantially during the study period, particularly after the advent of electronic medical record systems. The rapid increase in testing may suggest that electronic health records play a crucial role in test volume by facilitating easy ordering and could be leveraged to improved value-based serum ammonia ordering. Serum ammonia levels may also benefit from standardized guidelines on collection, laboratory analysis, and interpretation.     

Acute respiratory failure in immunosuppressed patients admitted to ICU

IntroductionThe number of hospitalized immunosuppressed adults is a growing and often develop severe complications that require admission to an Intensive Care Unit (ICU). The main cause of admission is acute respiratory failure (ARF). The goal of the study was to determine if ARF represents an independent risk factor for hospital mortality and in particular, we sought to ascertain if any risk factors were independently and identifiably associated with a bad outcome.MethodsWe perform a retrospective study of a prospectively collected data from patients admitted to an ICU. Adult patients with known immunosuppressive condition admitted to ICU were included.ResultsA total of 248 patients were included. Of 248 patients, 117 (47.2%) had a diagnosis of ARF at the time of ICU admission. Patients with ARF had a significantly higher in-hospital mortality (53.4% vs. 28.2% p = 0.001). Factors independently associated with hospital mortality were diagnosis of ARF at ICU admission, the presence of septic shock, use of continuous renal replacement therapy and failure of high-flow nasal canula(HFNC)/non-invasive (NIV) respiratory therapies.ConclusionWe identified ARF on admission and failure of HFNC/NIV to be independently associated with increased hospital mortality in immunosuppressed patients.