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Background & Aims Retention of bile acids (BAs) plays a central role in hepatic damage and disturbed BA signalling in liver disease. However, there is lack of data regarding the association of BAs with clinical complications, acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Thus, we aimed to evaluate the impact of circulating serum BAs for complications in patients with cirrhosis. Methods Therefore, 143 patients with established cirrhosis were included in this prospective cohort type observational study. Total serum BAs and individual BA composition were assessed in all patients on admission via high performance liquid chromatography. Clinical complications with respect to AD, ACLF as well as 1-year transplant-free survival were recorded. Results Total BAs and individual serum BAs were significantly higher in patients with bacterial infection, AD and ACLF (p

Background Hypoxic hepatitis (HH) is a frequent and potentially life-threatening event typically occurring in critically ill patients as a consequence of hemodynamic impairment. While acute kidney injury (AKI) has been well described in patients with acute liver failure, incidence and outcome of AKI accompanying HH are unclear. The aim of this study was to assess incidence, clinical implications and outcome of AKI and renal replacement therapy (RRT) in critically ill patients with HH. Methods A total of 1948 consecutive critically ill admissions were studied at the Medical University of Vienna. Laboratory and clinical parameters as well as the presence of HH and AKI were assessed on a daily basis. Outcome, renal recovery and length of stay were assessed and documented, and patients were followed for 1 year. Results A total of 295 admissions (15 %) developed HH. Main precipitators were cardiogenic (44 %) and septic shock (36 %). Occurrence of HH was significantly associated with AKI [OR 4.50 (95 % CI 3.30–6.12)] and necessity of renal replacement therapy [RRT; OR 3.36 (95 % CI 2.58–4.37)], p

Disturbances of coagulation and hemostasis are common in patients with liver cirrhosis. The typical laboratory pattern mimics disseminated intravascular coagulation (DIC). The aim of this study was to assess the impact of routine coagulation parameters in critically ill cirrhosis patients with regard to new onset of major bleeding and outcome. A total of 1,493 critically ill patients were studied prospectively. Routine coagulation parameters were assessed, and the DIC score was calculated based on platelets, fibrinogen, d-dimer, and prothrombin index. New onset of major bleeding during the stay at the intensive care unit and mortality were assessed. Patients were followed for 1 year. Two hundred eleven patients of the cohort had liver cirrhosis. Platelets, fibrinogen, prothrombin index, activated partial thromboplastin time, and d-dimer as well as the DIC score differed significantly between patients with and without cirrhosis (P0.001 for all). Moreover, fibrinogen, platelets, and activated partial thromboplastin time (but not prothrombin index) differed significantly between cirrhosis patients with and without major bleeding (P0.01 for all). Bleeding on admission, platelet count3010(9) /L, fibrinogen level60 mg/dL, and activated partial thromboplastin time values100 seconds were the strongest independent predictors for new onset of major bleeding in multivariate regression analysis. One-year mortality in cirrhosis patients with and without major bleeding was 89% and 68%, respectively (P0.05 between groups).Abnormal coagulation parameters and high DIC scores (primarily due to fibrinogen and platelets) correspond to increased bleeding risk in patients with liver cirrhosis in the intensive care unit, and fibrinogen and platelet count were identified as the best routine coagulation parameters for prediction of new onset of major bleeding; however, further studies are required to evaluate the potential therapeutic implications of these findings. (Hepatology 2016;64:556-568).

Background Hepatic impairment is found in up to 20 % in critically ill patients. Hypoxic/ischemic hepatitis (HH) is a diffuse hepatic damage associated with high morbidity and mortality. Indocyanine green plasma disappearance rate (ICG-PDR) is an effective tool assessing liver function in acute and chronic hepatic diseases. Aim of this study was to evaluate the prognostic impact of ICG-PDR in comparison to established parameters for risk stratification. Methods Patients with HH were included in this prospective observational study and compared to cirrhosis, acute liver failure (ALF) and patients without underlying liver disease. ICG-PDR, measured non-invasively by finger pulse densitometry, was assessed on admission and in patients with HH serially and results were compared between groups. Diagnostic test accuracy of ICG-PDR predicting 28-day mortality was analyzed by receiver operating characteristics (ROC). Results ICG-PDR on admission was significantly lower in patients with liver diseases than in patients without hepatic impairment (median 5.7 %/min, IQR 3.8–7.9 vs. 20.7 %/min, IQR 14.1–25.4 %/min; p

The incidence of hypoxic liver injury, most commonly referred to as hypoxic hepatitis (HH), is up to 10% in critically ill patients. In the majority of cases, HH occurs as a consequence of haemodynamic impairment following cardiogenic or septic shock. A marked, dramatic increase in the aminotransferase levels in a setting of cardiocirculatory failure is the key characteristic of HH. HH may contribute to several complications such as hepatopulmonary syndrome and hypoglycaemia. The overall mortality after the onset of HH is approximately 50–60% within 1 month. We report a case of severe HH that was successfully bridged using the Molecular Adsorbent Recirculating System. In addition to the possible effects of extracorporeal liver support devices, the recognition of HH and therapy of the underlying disease that led to the occurrence of HH is of central importance.

Hypoxic hepatitis (HH), also known as ischemic hepatitis or shock liver, is characterized by centrilobular liver cell necrosis and sharply increasing serum aminotransferase levels in a clinical setting of cardiac, circulatory or respiratory failure. Nowadays it is recognized as the most frequent cause of acute liver injury with a reported prevalence of up to 10% in the intensive care unit. Patients with HH and vasopressor therapy have a significantly increased mortality risk in the medical intensive care unit population. The main underlying conditions contributing to HH are low cardiac output and septic shock, although a multifactorial etiology is found in the majority of patients. HH causes several complications such as spontaneous hypoglycemia, respiratory insufficiency due to the hepatopulmonary syndrome, and hyperammonemia. HH reverses after successful treatment of the basic HH-causing disease. No specific therapies improving the hepatic function in patients with HH are currently established. Early recognition of HH and its underlying diseases and subsequent initiation of therapy is of central prognostic importance. The purpose of this review is to provide an update on the epidemiology, pathophysiology, and diagnostic and therapeutic options of HH.

Introduction Hyperchloremic acidosis is frequent in critically ill patients. Renal tubular acidosis (RTA) may contribute to acidemia in the state of hyperchloremic acidosis, but the prevalence of RTA has never been studied in critically ill patients. Therefore, we aimed to investigate the prevalence, type, and possible risk factors of RTA in critically ill patients using a physical-chemical approach. Methods This prospective, observational trial was conducted in a medical ICU of a university hospital. One hundred consecutive critically ill patients at the age ≥18, expected to stay in the ICU for ≥24 h, with the clinical necessity for a urinary catheter and the absence of anuria were included. Base excess (BE) subset calculation based on a physical-chemical approach on the first 7 days after ICU admission was used to compare the effects of free water, chloride, albumin, and unmeasured anions on the standard base excess. Calculation of the urine osmolal gap (UOG) - as an approximate measure of the unmeasured urine cation NH4+ - served as determinate between renal and extrarenal bicarbonate loss in the state of hyperchloremic acidosis. Results During the first week of ICU stay 43 of the patients presented with hyperchloremic acidosis on one or more days represented as pronounced negative BEChloride. In 31 patients hyperchloremic acidosis was associated with RTA characterized by a UOG ≤150 mosmol/kg in combination with preserved renal function. However, in 26 of the 31 patients with RTA metabolic acidosis was neutralized by other acid-base disturbances leading to a normal arterial pH. Conclusions RTA is highly prevalent in critically ill patients with hyperchloremic acidosis, whereas it is often neutralized by the simultaneous occurrence of other acid-base disturbances. Trial registration Clinicaltrials.gov NCT02392091. Registered 17 March 2015

Pruritus can occur as a severe complication of cholestasis. Several hypotheses suggest an important role for the accumulation of bile acids, endogenous opioids and - mire recently - lysophosphatidic acid. Bile acid sequestrants are the first-line therapeutic agents. In refractory cases, a stepwise approach using rifampicin, oral opiate antagonists and the selective serotonin reuptake inhibitor sertraline should be tested. Recent case series reported effective relief of pruritus using extracorporal liver support systems and plasmapheresis.

Hepatopulmonary syndrome (HPS) occurs in 20-30% of patients with liver cirrhosis and is associated with a2 fold increased mortality. Endothelial dysfunction seems to play a central role in its pathogenesis. von Willebrand factor antigen (vWF-Ag), an established marker of endothelial dysfunction, is significantly elevated in patients with liver cirrhosis, portal hypertension, and in experimental HPS. Aim of the present study was to evaluate the impact of vWF-Ag as a screening marker for presence of HPS in patients with stable cirrhosis.145 patients with stable liver cirrhosis were screened for presence of HPS in this prospective cohort type cross sectional diagnostic study. vWF-Ag and SaO2 levels were assessed at time of screening for HPS. Criteria of HPS were fulfilled in 31 (21%) patients.vWF-Ag levels were significantly higher in patients with HPS compared to patients without HPS (p0.001). Furthermore, vWF-Ag correlated significantly with gas exchange in HPS positive patients (p0.05). vWF-Ag is an independent predictor of HPS after correction for sex, age, model for endstage-liver disease (MELD), and hepatic venous pressure gradient (HVPG) (OR per 1% increase of vWF-Ag: 1.02, 95% CI: 1.00-1.04, p0.05). The best cut-off was 328% at a sensitivity of 100% and specificity of 53.5%; positive predictive value: 36.9%; negative predictive value: 100%.HPS is associated with elevated vWF-Ag levels. vWF-Ag may be a useful screening tool for early detection of HPS. Further studies investigating vWF-Ag in HPS will be needed to confirm our findings.

Women and men differ in substrate and energy metabolism. Such differences may affect energy requirements during the acute phase of critical illness.Data of 155 critically ill medical patients were reviewed for this study. Indirect calorimetry in each patient was performed within the first 72 h following admission to the medical intensive care unit after an overnight fast.In overweight (body mass index (BMI) ≥25 kg/m(2)) but not in normal-weight patients, resting energy expenditure (REE) adjusted for body weight (REEaBW) differed significantly between women and men (17.2 (interquartile range (IQR) 15.2-20.7) vs 20.9 (IQR 17.9-23.4) kcal/kg/day, P0.01). Similarly, REE adjusted for ideal body weight (REEaIBW) was significantly lower in women compared with men (25.5 (IQR 22.6-28.1) vs 28.0 (IQR 25.2-30.0) kcal/kg/day, P0.05). In overweight patients, gender was identified as an independent predictor of REEaBW in the multivariate regression model (r=-2.57 (95% CI -4.57 to -0.57); P0.05), even after adjustment for age, simplified acute physiology score (SAPS II), body temperature, body weight and height.REEaBW decreases with increasing body mass in both sexes. This relationship differs between women and men. Overweight critically ill women show significantly lower REEaBW and REEaIBW, respectively, compared with men. These findings could affect the current practice of nutritional support during the early phase of critical illness.

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.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.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.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.

Increased levels of arterial ammonia in patients with acute liver failure (ALF) are associated with increased mortality. There is a lack of data for prognostic impact of arterial ammonia in patients with acute-on-chronic liver failure (AoCLF) and hypoxic hepatitis (HH). We evaluated arterial ammonia levels and their prognostic relevance in patients with HH, ALF, AoCLF and without evidence for any liver disease.

Hypoxic hepatitis (HH) is the most frequent cause of acute liver injury in critically ill patients. No clinical data exist about new onset of jaundice in patients with HH. This study aimed to evaluate the incidence and clinical effect of jaundice in critically ill patients with HH. Two hundred and six consecutive patients with HH were screened for the development of jaundice during the course of HH. Individuals with preexisting jaundice or liver cirrhosis at the time of admission (n 5 31) were excluded from analysis. Jaundice was diagnosed in patients with plasma total bilirubin levels >3 mg/dL. One-year-survival, infections, and cardiopulmonary, gastrointestinal (GI), renal, and hepatic complications were prospectively documented. New onset of jaundice occurred in 63 of 175 patients with HH (36%). In patients who survived the acute event of HH, median duration of jaundice was 6 days (interquartile range, 3-8). Patients who developed jaundice (group 1) needed vasopressor treatment (P < 0.05), renal replacement therapy (P < 0.05), and mechanical ventilation (P < 0.05) more often and had a higher maximal administered dose of norepinephrine (P < 0.05), compared to patients without jaundice (group 2). One-year survival rate was significantly lower in group 1, compared to group 2 (8% versus 25%, respectively; P < 0.05). Occurrence of jaundice was associated with an increased frequency of complications during follow-up (54% in group 1 versus 35% in group 2; P < 0.05). In particular, infections as well as renal and GI complications occurred more frequently in group 1 during follow-up. Conclusion: Jaundice is a common finding during the course of HH. It leads to an increased rate of complications and worse outcome in patients with HH. (HEPATOLOGY 2012;56:2297-2304)

The disseminated intravascular coagulation (DIC) score is a predictor of outcome in critically ill patients [1,2]. Yet disturbances of coagulation and hemostasis, as reflected by the DIC score, are a common finding in patients with liver cirrhosis. Thus, it is unclear whether the DIC score has prognostic value in critically ill patients with liver cirrhosis. The aim of this study was to assess the applicability and prognostic impact of the DIC score in critically ill patients with liver cirrhosis.

Hypoxic hepatitis (HH) is a frequent cause of acute hepatocellular damage in critically ill patients associated with high mortality. Indocyanine green, a medical dye, is removed solely by the liver without entering enterohepatic circulation. Therefore its plasma disappearance rate (ICG-PDR) is an effective clinical tool for assessment of liver function in acute and chronic hepatic disease.

The disseminated intravascular coagulation (DIC) score is a predictor of outcome in critically ill patients [1]. Yet, disturbances of coagulation are a common finding in patients with liver cirrhosis. Thus, the prognostic value of the DIC score and its subcomponents in patients with liver cirrhosis is unclear.

We present a semi-automated point-of-care (POC) sensor approach for the simultaneous and reagent-free determination of clinically relevant parameters in blood plasma. The portable sensor system performed direct mid-infrared (MIR) transmission measurements of blood plasma samples using a broadly tunable external-cavity quantum cascade laser source with high spectral power density. This enabled the use of a flow cell with a long path length (165 μm) which resulted in high signal-to-noise ratios and a rugged system, insensitive to clogging. Multivariate calibration models were built using well established Partial-Least-Squares (PLS) regression analysis. Selection of spectral pre-processing procedures was optimized by an automated evaluation algorithm. Several analytes, including glucose, lactate, triglycerides, cholesterol, total protein as well as albumin, were successfully quantified in routinely taken blood plasma samples from 67 critically ill patients. Although relying on a spectral range from 1030 cm(-1) to 1230 cm(-1), which is optimal for glucose and lactate but rather unusual for protein analysis, it was possible to selectively determine the albumin and total protein concentrations with sufficient accuracy for POC application.

(r =0.852, P 0.05). By contrast, after PE treatment the mean levels of AOPP were markedly decreased in the survival group (from 66.16±16.47 to 25.12±6.46umol/L, P < 0.001) in contrast to the nonsurvival group (from 76.22±14.66 to 45.26±17.86umol/L, P < 0.001) (P < 0.001). Conclusions: AOPP can assess and monitor the levels of oxidative stress in ACLF patients. The changes of AOPP after PE treatment maybe contribute to predict the prognosis. Acknowledgements: Our research was supported primarily by research grants from the national basic research program of China, No. 2007CB512801; the national 11th 5-year plan for hepatitis research, No. 2008ZX10002–005 and Tianjin public health bureau key research program, No. 07KG9.

Sudden cardiac arrest (CA) is one of the leading causes of death in adults in many parts of the world [1]. Every year estimated 350.000 to 700.000 people in Europe are suffering CA and receive cardiopulmonary resuscitation (CPR) [2]. To date, there is no data available on CA and CPR in patients with liver cirrhosis.