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Predictors of poor outcome associated with variceal bleeding remain suboptimal. In patients with cirrhosis, serum lactate combined with Model for End-Stage Liver Disease (MELD-LA) improved prediction across heterogeneous populations. However, prognostic properties have not yet been assessed in the context of variceal bleeding.We aimed to evaluate the predictive performance of MELD-LA compared to MELD, lactate, and nadir hemoglobin in cirrhosis patients with variceal bleeding.In this multicenter study, we identified 472 patients with variceal bleeding from a German primary cohort (University Hospitals Hamburg/Frankfurt/Cologne), and two independent external validation cohorts [Veterans Affairs (VA), Baylor University]. Discrimination for 30-day mortality was analyzed and scores were compared. MELD-LA was evaluated separately in validation cohorts to ensure consistency of findings.In contrast to nadir hemoglobin, MELD and peak-lactate at time of bleeding were significantly higher in 30-day non-survivors in the primary cohort (p = 0.708; p 0.001). MELD-LA had excellent discrimination for 30-day mortality (AUROC 0.82, 95% CI 0.76-0.88), better than MELD and peak-lactate (AUROC 0.78, 95% CI 0.71-0.84; AUROC 0.73, 95% CI 0.66-0.81). MELD-LA predicted 30-day mortality independently of age, sex, severity of liver disease and vasopressor support (HR 1.29 per 1-point-increase of MELD-LA; 95% CI 1.19-1.41; p 0.001). Similarly, MELD-LA demonstrated excellent discrimination for 30-day mortality in the VA (AUROC = 0.86, 95% CI 0.79-0.93) and Baylor cohort (AUROC = 0.85, 95% CI 0.74-0.95).MELD-LA significantly improves discrimination of short-term mortality associated with variceal bleeding, compared to MELD, peak-lactate and nadir hemoglobin. Thus, MELD-LA might represent a useful and objective marker for risk assessment and therapeutic intervention in patients with variceal bleeding.

Blutungsereignisse sind gefurchtete Komplikationen bei kritisch kranken Patienten auf der Intensivstation. Je nach Lokalisation und Schweregrad der Blutungen sind diese haufig mit erhohter Morbiditat und Mortalitat vergesellschaftet. Die klinische Bedeutung der unterschiedlichen Blutungskomplikationen ergeben sich einerseits aus der Blutungslokalisation (z. B. intrazerebrale Blutung), der Blutungsintensitat (z. B. fulminante Osophagusvarizenblutung), andererseits aber auch aus der Haufigkeit (z. B. gastrointestinale Blutung). In jedem Fall besteht die Therapie aus der Stabilisierung des Patienten, dem Stoppen der Blutung und der Verhinderung von Folge- und Begleitkomplikationen. In der aktuellen Ubersicht sollen wichtige Ursachen und Aspekte im Hinblick auf Blutungen bei kritisch kranken Patienten erortert werden.

Background Heyde syndrome (HS) is known as the association of severe aortic stenosis (AS) and recurrent gastrointestinal bleeding (GIB) from angiodysplasia. Data on the prevalence of HS and results after TAVI remain scarce. Methods 2548 consecutive patients who underwent TAVI for the treatment of AS from 2008 to 2017 were evaluated for a history of GIB and the presence of HS. The diagnosis of HS was defined as a clinical triad of severe AS, a history of recurrent GIB, and an endoscopic diagnosis of angiodysplasia. These patients (Heyde) were followed to investigate clinical outcomes, bleeding complications and the recurrence of GIB and were compared to patients with GIB unrelated to HS (Non-Heyde). Results A history of GIB prior to TAVI was detected in 190 patients (7.5%). Among them, 47 patients were diagnosed with HS (1.8%). Heyde patients required blood transfusions more frequently compared to Non-Heyde patients during index hospitalization (50.0% vs. 31.9%, p = 0.03). Recurrent GIB was detected in 39.8% of Heyde compared to 21.2% of Non-Heyde patients one year after TAVI (p = 0.03). In patients diagnosed with HS and recurrent GIB after TAVI, the rate of residual ≥ mild paravalvular leakage (PVL) was higher compared to those without recurrent bleeding (73.3% vs. 38.1%, p = 0.05). Conclusion A relevant number of patients undergoing TAVI were diagnosed with HS. Recurrent GIB was detected in a significant number of Heyde patients during follow-up. A possible association with residual PVL requires further investigation to improve treatment options and outcomes in patients with HS. Graphic abstract

In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients.In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort.Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly.This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.

Background Prophylactic endoscopic variceal band ligation (EVL) is frequently performed in patients with liver cirrhosis. The aim of our study was to identify factors associated with early upper gastrointestinal bleeding (UGIB) in cirrhosis patients after prophylactic EVL. Methods 787 nonemergency EVLs performed in 444 patients in two German University medical centers were analyzed retrospectively. Results Within 30 days after EVL, 38 UGIBs were observed (4.8 % of all procedures). Bilirubin levels (hazard ratio [HR] 1.5, 95 % confidence interval [CI] 1.2–2.0 for a 2-fold increase) and presence of varices grade III/IV according to Paquet (HR 2.6, 95 %CI 1.3–5.0 compared with absence or smaller sized varices) were independently associated with UGIB following EVL. International normalized ratio (INR) was associated with bleeding events in the univariate analysis but did not reach statistical significance after adjustment for bilirubin and presence of varices grade III/IV (HR 1.2, 95 %CI 0.9–1.6 for an increase by 0.25). There was no statistically significant association between platelet count or fibrinogen levels and UGIB. Substitution of coagulation products did not affect incidence of bleeding after EVL, which also applied to patients with “coagulopathy” (INR > 1.5 and/or platelet count Conclusions EVL is a safe procedure and immediate bleeding complications are rare. Serum bilirubin levels and size of varices, rather than coagulation indices, are associated with UGIB after EVL. Our data do not support the preventive substitution of blood or coagulation products.

Bleedings are frequent and clinically important complications in critically ill patients in the intensive care unit, and-depending on location and intensity-are associated with high morbidity and mortality. The clinical impact of different bleeding entities is affected by the location (e.g. intracerebral bleedings), the severity (e.g. fulminant variceal bleeding) and the incidence (e.g. gastrointestinal bleeding) of the respective bleeding type. Therapy varies among bleeding entities, but consists of stabilization of the patient, control of the bleeding, and prevention of complications. This review describes relevant therapeutic aspects of selected bleeding complications in critically ill patients.Blutungsereignisse sind gefürchtete Komplikationen bei kritisch kranken Patienten auf der Intensivstation. Je nach Lokalisation und Schweregrad der Blutungen sind diese häufig mit erhöhter Morbidität und Mortalität vergesellschaftet. Die klinische Bedeutung der unterschiedlichen Blutungskomplikationen ergeben sich einerseits aus der Blutungslokalisation (z. B. intrazerebrale Blutung), der Blutungsintensität (z. B. fulminante Ösophagusvarizenblutung), andererseits aber auch aus der Häufigkeit (z. B. gastrointestinale Blutung). In jedem Fall besteht die Therapie aus der Stabilisierung des Patienten, dem Stoppen der Blutung und der Verhinderung von Folge- und Begleitkomplikationen. In der aktuellen Übersicht sollen wichtige Ursachen und Aspekte im Hinblick auf Blutungen bei kritisch kranken Patienten erörtert werden.

Zusammenfassung Einleitung Protonenpumpeninhibitoren (PPIs) gehören zu den weltweit am häufigsten verordneten Medikamenten. Vor allem bei Patienten mit Leberzirrhose wurden Verschreiberaten von bis zu 78 % berichtet. PPIs scheinen mit relevanten Nebenwirkungen, wie erhöhtem Risiko für nosokomiale Infektionen, spontan bakterieller Peritonitis oder dem Auftreten einer hepatischen Enzephalopathie assoziiert zu sein. Aus diesem Grund war es Ziel dieser Umfrage, die Verschreibungspraxis von PPIs bei Patienten mit Leberzirrhose in Deutschland zu erheben. Methoden Die Daten wurden mittels Web-basierter Befragung erhoben. Hierfür wurde eine Einladung über die Newsletter der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), des Berufsverbandes Gastroenterologie Deutschland (BVGD) und der Arbeitsgemeinschaft universitärer Gastroenterologen (AUG) versandt. Ergebnisse 61 Personen haben an der Umfrage teilgenommen. Insgesamt wurden sehr hohe PPI-Verschreiberaten von 58 % im stationären, sowie 44 % im ambulanten Bereich berichtet. Beinahe die Hälfte der Befragten gab an, PPIs bei medizinisch fraglicher Indikation einzusetzen (z. B. unspezifische abdominelle Beschwerden). Bei einem Drittel der Patienten könnte die bestehende PPI-Therapie nach kritischer Evaluation wieder beendet werden. 55 % der Befragten gaben an, dass PPIs ihrer Einschätzung zufolge mit relevanten Nebenwirkungen assoziiert sind. Blutungskomplikationen nach Absetzen einer PPI-Therapie wurden durch die Befragten selten beobachtet. Schlussfolgerung PPIs werden bei Patienten mit Leberzirrhose in Deutschland sehr häufig verordnet. Ein Problembewusstsein bezüglich eines insgesamt unklaren Risiko-Nutzen-Verhältnisses scheint vorhanden zu sein. Prospektive Untersuchungen sind dringend nötig, um die Evidenzlage hinsichtlich Indikation und Dauer einer PPI-Therapie bei Patienten mit Leberzirrhose zu erhärten.

Background & Aims Refractory ascites is the main reason for the implantation of a transjugular intrahepatic portosystemic shunt (TIPS) in liver cirrhosis, but ascites control by TIPS fails in a relevant proportion of cases. Here, we investigated whether routine parameters pre-TIPS can predict persistent ascites after TIPS implantation and whether persistent ascites predicts long-term clinical outcome. Methods A detailed retrospective analysis of 128 patients receiving expanded polytetrafluoroethylene-covered stents for the treatment of refractory ascites was performed. Persistent ascites post-TIPS was defined as the prolonged need for paracentesis >3 months after TIPS. The influence of demographics, laboratory results, pre-TIPS heart and liver ultrasound results, and invasive hemodynamic parameters on persistent ascites was evaluated by univariable and multivariable logistic regression. Predictors of the composite endpoint liver transplantation/death were analyzed using a multivariable Cox regression. Results Ascites control post-TIPS was achieved in 95/128 patients (74%), whereas ascites remained persistent in 33/128 cases (26%). On multivariable analysis, a lower paracentesis frequency pre-TIPS (odds ratio 1.672; 95% CI 1.253–2.355) and lower baseline creatinine levels (odds ratio 2.640; CI 1.201–6.607) were associated with ascites control. Patients with persistent ascites post-TIPS had and impaired transplant-free survival (median 10.0 vs. 25.8 months), for which persistent ascites was the only independent predictor (hazard ratio 5.654; CI 3.019–10.59). Conclusion TIPS-placement in patients with lower paracentesis frequency and creatinine levels is associated with superior ascites control. Thus, TIPS implantation should be considered in moderate decompensation and not as a last resort. Persistent ascites post-TIPS seems to be the only predictor of liver transplantation and death. Lay summary The insertion of a transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory ascites should be considered in patients with moderate decompensation and not as a last resort, as lower paracentesis frequency and creatinine levels pre-TIPS are associated with superior ascites control. In turn, failure to control ascites seems to be the only predictor of liver transplantation and death., Graphical abstract Unlabelled Image, Highlights • Ascites control post-TIPS is superior if the TIPS is placed at lower paracentesis frequency and creatinine levels. • Transplant-free survival is decreased in patients with a failed ascites control post-TIPS. • TIPS-placement should be considered “early” in ascitic decompensation. • Close monitoring and prioritized organ allocation should be considered in patients with failed ascites control post-TIPS.

Hypoxic liver injury (HLI) is a frequent and life-threatening complication in critically ill patients that occurs in up to ten percent of critically ill patients. However, there is a lack of data on HLI following cardiac arrest and its clinical implications on outcome. Aim of this study was to investigate incidence, outcome and functional outcome of patients with HLI after in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA).We conducted an analysis of a cardiac arrest registry data over a 7-year period. All patients with non-traumatic OHCA and IHCA with return of spontaneous circulation (ROSC) treated at the emergency department of a tertiary care hospital were included in the study. HLI was defined according to established criteria. Predictors of HLI, occurrence, clinical and neurological outcome were assessed using multivariable regression.Out of 1068 patients after IHCA and OHCA with ROSC, 219 (21%) patients developed HLI. Rate of HLI did not differ significantly in IHCA and OHCA patients. Multivariate regression analysis identified time-to-ROSC [OR 1.18, 95% CI (1.01-1.38); p 0.05], presence of cardiac failure [OR 2.57, 95% CI (1.65-4.01); p 0.001] and Charlson comorbidity index [OR 0.83, 95% CI (0.72-0.95); p 0.01] as independent predictors for occurrence of HLI. Good functional outcome was significantly lower in patients suffering from HLI after 28-days (35% vs. 48%, p 0.001) and 1-year (34% vs. 44%, p 0.001). Occurrence of HLI was associated with unfavourable neurological outcome [OR 1.74, 95% CI (1.16-2.61); p 0.01] in multivariate regression analysis.New onset of HLI is a frequent finding after IHCA and OHCA. HLI is associated with increased mortality, unfavourable neurological and overall outcome.

Background SARS-CoV-2 caused a pandemic and global threat for human health. Presence of liver injury was commonly reported in patients with coronavirus disease 2019 (COVID-19). However, reports on severe liver dysfunction (SLD) in critically ill with COVID-19 are lacking. We evaluated the occurrence, clinical characteristics and outcome of SLD in critically ill patients with COVID-19. Methods Clinical course and laboratory was analyzed from all patients with confirmed COVID-19 admitted to ICU of the university hospital. SLD was defined as: bilirubin ≥ 2 mg/dl or elevation of aminotransferase levels (> 20-fold ULN). Results 72 critically ill patients were identified, 22 (31%) patients developed SLD. Presenting characteristics including age, gender, comorbidities as well as clinical presentation regarding COVID-19 overlapped substantially in both groups. Patients with SLD had more severe respiratory failure (paO2/FiO2: 82 (58–114) vs. 117 (83–155); p p p = 0.106), vasopressor (95% vs. 72%; p p p p = 0.002). Occurrence of SLD was independently associated with presence of viremia [OR 6.359; 95% CI 1.336–30.253; p p p p Conclusion One-third of critically ill patients with COVID-19 suffer from SLD, which is associated with high mortality. Occurrence of viremia and severity of illness seem to contribute to occurrence of SLD and underline the multifactorial cause.

Background Non-invasive scores, such as the non-alcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS), are increasingly used for liver fibrosis assessment in patients with NAFLD. The aim of this study was to assess the applicability and reliability of non-invasive fibrosis scores in NAFLD patients with and without morbid obesity. Methods Three hundred sixty-eight patients with biopsy-proven NAFLD identified between January 2012 and December 2015 were studied; 225 with morbid obesity (biopsy obtained during bariatric surgery) and 143 patients without (termed as “conventional”). Results Median age was 47 years, 57% were female. Median body mass index (BMI) was 42.9 kg/m2 with significant differences between our conventional and morbidly obese patients (BMI 29.0 vs. 50.8 kg/m2, p p 2 improved NFS’ overall performance (AUROC 0.838). FIB-4 > 1.0 indicated high probability of advanced fibrosis (OR = 29.1). FIB-4 predicted advanced fibrosis independently from age, sex, BMI, and presence of morbid obesity. Conclusions Our data suggest that FIB-4 score is an accurate predictor of advanced fibrosis in NAFLD throughout all BMI stages. Without adjustment, NFS tends to overestimate fibrosis in morbidly obese NAFLD patients. This problem may be solved by implementation of an upper BMI limit (for NFS) or adjustment of diagnostic thresholds.

Multiple factors are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), but the exact immunological mechanisms that cause inflammation and fibrosis of the liver remain enigmatic. In this current study, cellular samples of a cohort of NAFLD patients (peripheral blood mononuclear cells (PBMC): n = 27, liver samples: n = 15) and healthy individuals (PBMC: n = 26, liver samples: n = 3) were analyzed using 16-color flow cytometry, and the frequency and phenotype of 23 immune cell subtypes was assessed. PBMC of NAFLD patients showed decreased frequencies of total CD3+, CD8+ T cells, CD56dim NK cells and MAIT cells, but elevated frequencies of CD4+ T cells and Th2 cells compared to healthy controls. Intrahepatic lymphocytes (IHL) of NAFLD patients showed decreased frequencies of total T cells, total CD8+ T cells, Vd2+γδ T cells, and CD56bright NK cells, but elevated frequencies of Vδ2-γδ T cells and CD56dim NK cells compared to healthy controls. The activating receptor NKG2D was significantly less frequently expressed among iNKT cells, total NK cells and CD56dim NK cells of PBMC of NAFLD patients compared to healthy controls. More strikingly, hepatic fibrosis as measured by fibroscan elastography negatively correlated with the intrahepatic frequency of total NK cells (r2 = 0,3737, p = 0,02). Hepatic steatosis as measured by controlled attenuation parameter (CAP) value negatively correlated with the frequency of circulating NKG2D+ iNKT cells (r2 = 0,3365, p = 0,0047). Our data provide an overview of the circulating and intrahepatic immune cell composition of NAFLD patients, and point towards a potential role of NK cells and iNKT cells for the regulation of hepatic fibrosis and steatosis in NAFLD.

Hyperglycemia is common in critically ill patients and associated with increased mortality. It has been suggested that different nutrition formulas may beneficially influence glucose levels in surgical intensive care patients. In this prospective randomized clinical cohort study we investigated glucose homeostasis in response to different enteral nutrition formulas in medical critically ill patients.60 medical critically ill patients were randomized to receive continuous fat-based (group A, n = 30) or glucose-based enteral nutrition (group B, n = 30) for seven days. Indirect calorimetry was performed to determine energy demand at baseline and on days 3 and 7. Glucose levels and area under the curve (AUC), insulin demand, glucose variability, and calorie and substrate intake per 24 h were assessed for 7 days.Over the course of 7 days patients had similar average daily glucose (p = 0.655), glucose AUC (A: 758 (641-829) mg/dl/day vs B: 780 (733-845) mg/dl/day, p = 0.283), similar overall insulin demand (A: 153.5 (45.3-281.5) IE vs B: 167.9 (82.3-283.8) IE, p = 0.525), and received similar amounts of enteral nutrition per 24 h. Resting energy expenditure was similar at baseline (A: 1556 (1227-1808) kcal/day vs B: 1563 (1306-1789) kcal/day, p = 0.882) but energy expenditure increased substantially over time in group A (p 0.0001), but not in group B (p = 0.097).Fat-based and glucose-based EN influence glucose homeostasis and insulin demand similarly, yet diet-induced thermogenesis was substantially higher in critically ill patients receiving fat-based enteral nutrition.

Zusammenfassung Einleitung Die nicht-alkoholische Fettlebererkrankung (NAFLD) gehört mittlerweile weltweit zu den häufigsten Ursachen für eine chronische Leberschädigung. Aktuell sind die therapeutischen Optionen limitiert und neue pharmakologische Therapieoptionen werden primär im Rahmen von Studien untersucht. Da viele aktuelle Studien zumeist auf NAFLD-Patienten mit den Fibrosestadien II und III (nach Kleiner) abzielen, ist die nicht-invasive Identifikation dieser Patienten von zunehmender Bedeutung. Ziel Evaluation von Lebersteifigkeitsmessung (LSM) und NAFLD Fibrosis Score (NFS) im Hinblick auf die Vorhersage eines Fibrosestadiums II/III. Methoden Patienten mit bioptisch gesicherter NAFLD Diagnose wurden in die Studie eingeschlossen. Vor der Leberbiopsie wurden alle Patienten klinisch, laborchemisch und mittels LSM evaluiert. Anschließend wurde die Vorhersagekraft von NFS und LSM im Hinblick auf das Vorliegen einer Fibrose Stadium II/III untersucht. Ergebnisse 134 NALFD-Patienten wurden in die Studie eingeschlossen und untersucht. Das mittlere Alter betrug 53 (IQR 36 – 60) Jahre, 55 Patienten (41 %) waren weiblich. 82 % der Patienten waren übergewichtig/adipös mit typischen Befundkonstellationen des Metabolischen Syndroms. 84 Patienten (66 %) zeigten Zeichen einer Fibrose, bei 42 (50 %) bestand eine fortgeschrittene Fibrose. LSM und NFS korrelierten mit dem Fibrosestadium (r = 0,696 bzw. r = 0,685, p Schlussfolgerung Die Kombination von LSM und NFS ermöglicht die Identifikation von Patienten mit erhöhtem Risiko für ein Fibrosestadium II/III. Daher könnte der Einsatz dieser beiden nicht-invasiven Tests speziell in Kombination als Screening-Tool für NAFLD-Patienten im Hinblick auf das Vorhandensein einer Fibrose II/III eingesetzt werden. Durch den Einsatz dieser Verfahren könnten außerdem nicht-notwendige Biopsien vermieden werden.

Background Organ failure increases mortality in patients with liver cirrhosis. Data about resuscitated cardiac arrest patients with liver cirrhosis are missing. This study aims to assess aetiology, survival and functional outcome in patients after successful cardiopulmonary resuscitation (CPR) with and without liver cirrhosis. Methods Analysis of prospectively collected cardiac arrest registry data of consecutively hospital-admitted patients following successful CPR was performed. Patient’s characteristics, admission diagnosis, severity of disease, course of disease, short- and long-term mortality as well as functional outcome were assessed and compared between patients with and without cirrhosis. Results Out of 1068 patients with successful CPR, 47 (4%) had liver cirrhosis. Acute-on-chronic liver failure (ACLF) was present in 33 (70%) of these patients on admission, and four patients developed ACLF during follow-up. Mortality at 1 year was more than threefold increased in patients with liver cirrhosis (OR 3.25; 95% CI 1.33–7.96). Liver cirrhosis was associated with impaired neurological outcome (OR for a favourable cerebral performance category: 0.13; 95% CI 0.04–0.36). None of the patients with Child–Turcotte–Pugh (CTP) C cirrhosis survived 28 days with good neurological outcome. Overall nine (19%) patients with cirrhosis survived 28 days with good neurological outcome. All patients with ACLF grade 3 died within 28 days. Conclusion Cardiac arrest survivors with cirrhosis have worse outcome than those without. Although one quarter of patients with liver cirrhosis survived longer than 28 days after successful CPR, patients with CTP C as well as advanced ACLF did not survive 28 days with good neurological outcome. Electronic supplementary material The online version of this article (doi:10.1186/s13613-017-0322-1) contains supplementary material, which is available to authorized users.

Interactions between the hepatic portal and cardiovascular systems are frequently found in patients with liver disease. Cirrhotic cardiomyopathy (CCMP) is defined as reduced cardiac function in patients with liver cirrhosis in the absence of other known causes of cardiac disease. The typical hyperdynamic circulatory state by means of increased cardiac output and reduced systemic vascular resistance may mask left ventricular failure. Portopulmonary hypertension (POPH) is defined as increased pulmonary arterial pressure and the presence of portal hypertension, and is associated with increased mortality. Targeted medical therapies include vasodilators such as prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Hypoxic or ischaemic hepatitis (HH) is defined by a sharp increase of serum aminotransferase levels due to liver cell necrosis as result of cardiac, circulatory or respiratory failure. An overview of these diseases is provided in this article.

Background & Aims Current guidelines discourage renal replacement therapy (RRT) in critically ill cirrhotics in the lack of liver transplant (LT) options. This study aimed to identify patients who benefit from RRT in the short and long-term. Methods Critically ill cirrhotics were included over a time period of 6 years and followed for at least 1 year. CLIF-C ACLF, CLIF-SOFA, SOFA and MELD scores on admission, 24 h prior to RRT, 24 and 48 hours after start of RRT were analysed for their predictive value of ICU-mortality. Additionally, long-term renal recovery and successful bridging to LT was assessed. Results In total, 40% (78/193) of patients required RRT. ICU-, 28 days-, 90 days-, and 1 year-mortality was 71%, 83%, 91%, and 92%, respectively, and was significantly higher than in patients without need for RRT (4%, 30%, 43%, and 50%), P

Fragestellung Das hepatopulmonale Syndrom (HPS) ist eine Storung der arteriellen Oxygenierung, welche bei bis zu 30 % der Patienten mit Leberzirrhose auftritt und mit deutlich erhohter Sterblichkeit einhergeht. Ikterus und cholestatische Dysfunktion sind von zentraler pathogenetischer Rolle in akuter als auch chronischer Lebererkrankung. Ziel Deshalb war es Ziel dieser Studie den Stellenwert der Serum-Gallensauren bei Patienten mit HPS zu untersuchen. Methodik 74 Patienten mit Leberzirrhose wurden in diese Studie eingeschlossen. Cholestasemarker, Gesamt- als auch individuelle Gallensauren wurden bestimmt und alle Patienten auf das Vorhandensein von HPS gescreent. 26 Patienten (35 %) erfullten die Kriterien fur HPS. Ergebnisse Serum-Gallensauren waren signifikant hoher bei Patienten mit HPS im Vergleich zu denen ohne (mediane Gesamt-Gallensauren 83,5 μmol/l, IQR 43,1 – 148,9 vs. 26,9 μmol/l, 11 – 75,6; p Schlussfolgerung Serum-Gallensauren sind mit dem Vorhandensein von HPS assoziiert und korrelieren mit dem Schweregrad der Butgasaustauschstorung. Zukunftige Studien sollten den Stellenwert der Gallensauren bei HPS sowie den Einfluss einer direkten Regulation des Gallensaure-Metabolismus untersuchen. Background Hepatopulmonary syndrome (HPS) occurs in 20 – 30 % of patients with cirrhosis and is associated with increased mortality. Cholestasis and accumulation of bile acids (BAs) play a major role in chronic liver disease. Aim We aimed to evaluate the clinical role of serum BAs in patients with HPS. Methods Seventy-four patients with cirrhosis were included in this prospective study. Marker for cholestasis as total and individual serum BAs, bilirubin, alkaline phosphatase (AP), and gamma-glutamyl transpeptidase (GGT) were analyzed in patients screened for HPS. Criteria of HPS were fulfilled in 26 patients (35 %). Results In contrast to AP and GGT, bilirubin and serum BAs were significantly elevated in patients with HPS (median total BAs in HPS 83.5 μmol/L, IQR 43.1 – 148.9 vs. no HPS 26.9 μmol/L, 11 – 75.6; p Conclusion BA retention is associated with HPS and gas exchange abnormalities. Future studies should assess whether modulation of BAs signaling may impact the course of HPS.

Introduction Heyde syndrome is known as the association of severe aortic stenosis (AS) and recurrent gastrointestinal bleeding (GIB) from angiodysplasia. To date only few data exist regarding the prevalence of Heyde syndrome and results after transcatheter aortic valve implantation (TAVI) for the treatment of AS. Purpose We sought to evaluate the prevalence of Heyde syndrome in a routine clinical cohort of patients undergoing TAVI and analyze the effectiveness of treatment of AS regarding recurrent GIB in these patients. Methods We conducted a retrospective single-center analysis of 2545 consecutive patients who underwent TAVI for the treatment of AS in 2008–2017. Patients with a history of GIB were identified. The diagnosis of Heyde syndrome was defined as a clinical triad of presence of severe AS, a history of recurrent GIB, and an endoscopic diagnosis of angiodysplasia. GIB of unknown origin or related to other causes was defined as bleeding unrelated to angiodysplasia. Clinical outcomes of patients with Heyde syndrome were evaluated with emphasis on bleeding complications and recurrence of GIB. Results A history of GIB prior to TAVI was detected in 190 patients (7.5%) of the TAVI cohort. Among them, 143 patients had a GIB unrelated to angiodysplasia (5.6%) and 47 patients (1.8%) were diagnosed with Heyde syndrome. Median age and STS-PROM were 80.7 (75.3, 84.0) years and 4.7 (2.7, 9.0) respectively in Heyde patients. TAVI was successfully performed in all cases (66% endovascular access, 34% transapical access). The effective orifice areas increased from 0.8±0.1 cm2 to 2.1±0.5 cm2. Periprocedural major/life-threatening bleeding was found in 6 patients (12.8%), mainly access-related and none due to GIB. In 51% of Heyde-patients transfusion of 4.5±5.7 packed red blood cells was required during the index hospitalisation. During a mean follow-up of 12 months, recurrent GIB after TAVI was detected in 32% of patients with Heyde syndrome. In contrast only 18% of patients with GIB unrelated to angiodysplasia (Non-Heyde) had recurrent GIB after TAVI. In patients diagnosed with Heyde syndrome and recurrent GIB after TAVI the rate of residual mild or moderate paravalvular regurgitation was higher compared to those with an unremarkable course (73% vs. 37%, p=0.045). Figure 1. 1-year Follow-Up Conclusions A relevant number of patients presenting for treatment of AS can be diagnosed with Heyde syndrome. In these patients TAVI can be successfully performed with moderate incidence of periprocedural bleeding complications but significant transfusion rates. Regardless of successful treatment of AS, recurrent GIB was detected in a significant number of Heyde patients during follow-up. The possible association with residual paravalvular regurgitation requires further investigation to improve treatment options in patients with Heyde syndrome.

Proton pump inhibitors (PPI) are one of the most frequently prescribed drugs worldwide. In particular, in patients with liver cirrhosis prescription rates up to 78 % have been reported. PPI may be a risk factor for nosocomial infections, spontaneous bacterial peritonitis and onset of hepatic encephalopathy. Aim of this survey was to assess the prescription practice of PPI in patients with cirrhosis in Germany. We performed a web-based survey among hepatologists and gastroenterologists. The invitations for the survey have been sent out via the newsletter of German gastroenterological societies (DGVS, BVGD and AUG). 61 persons have participated in the survey. Overall, high PPI prescription rates have been reported (58 % in inpatient and 44 % in outpatient setting). Almost half of the respondents reported that PPI are frequently prescribed without clear indication (such as abdominal discomfort). One third reported that the PPI therapy could be stopped after critical evaluation of the indication. 55 % of the respondents stated that according to their estimates PPI are associated with adverse reactions. Bleeding was only very rarely seen after termination of PPI treatment. PPI are frequently prescribed among patients with liver cirrhosis in Germany. Prescribers are aware of an unclear risk-benefit ratio. Further prospective data are urgently needed to increase evidence regarding indication and duration of PPI therapy in patients with cirrhosis. Protonenpumpeninhibitoren (PPIs) gehören zu den weltweit am häufigsten verordneten Medikamenten. Vor allem bei Patienten mit Leberzirrhose wurden Verschreiberaten von bis zu 78 % berichtet. PPIs scheinen mit relevanten Nebenwirkungen, wie erhöhtem Risiko für nosokomiale Infektionen, spontan bakterieller Peritonitis oder dem Auftreten einer hepatischen Enzephalopathie assoziiert zu sein. Aus diesem Grund war es Ziel dieser Umfrage, die Verschreibungspraxis von PPIs bei Patienten mit Leberzirrhose in Deutschland zu erheben. Die Daten wurden mittels Web-basierter Befragung erhoben. Hierfür wurde eine Einladung über die Newsletter der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), des Berufsverbandes Gastroenterologie Deutschland (BVGD) und der Arbeitsgemeinschaft universitärer Gastroenterologen (AUG) versandt. 61 Personen haben an der Umfrage teilgenommen. Insgesamt wurden sehr hohe PPI-Verschreiberaten von 58 % im stationären, sowie 44 % im ambulanten Bereich berichtet. Beinahe die Hälfte der Befragten gab an, PPIs bei medizinisch fraglicher Indikation einzusetzen (z. B. unspezifische abdominelle Beschwerden). Bei einem Drittel der Patienten könnte die bestehende PPI-Therapie nach kritischer Evaluation wieder beendet werden. 55 % der Befragten gaben an, dass PPIs ihrer Einschätzung zufolge mit relevanten Nebenwirkungen assoziiert sind. Blutungskomplikationen nach Absetzen einer PPI-Therapie wurden durch die Befragten selten beobachtet. PPIs werden bei Patienten mit Leberzirrhose in Deutschland sehr häufig verordnet. Ein Problembewusstsein bezüglich eines insgesamt unklaren Risiko-Nutzen-Verhältnisses scheint vorhanden zu sein. Prospektive Untersuchungen sind dringend nötig, um die Evidenzlage hinsichtlich Indikation und Dauer einer PPI-Therapie bei Patienten mit Leberzirrhose zu erhärten.

Alterations in hemostasis are a characteristic feature of advanced liver disease. Patients with coagulopathy of advanced liver disease are prone to bleedings and also thromboembolic events. Under stable conditions, cirrhosis patients show alterations in both pro- and anticoagulatory pathways, frequently resulting in a rebalanced hemostasis. This review summarizes current recommendations of management during bleeding and prior to invasive procedures in patients with cirrhosis.

The frequency of acquired liver injury and failure in critical illness has been significantly increasing over recent decades. Currently, liver injury and failure are observed in up to 20% of patients in intensive care units and are associated with significantly increased morbidity and mortality. Secondary forms of liver injury in critical illness are divided primarily into cholestatic, hypoxic, or mixed forms. Therefore, sufficient knowledge of underlying alterations (e.g., hemodynamic, inflammatory, or drug induced) is key to a better understanding of clinical manifestations, prognostic implications, as well as diagnostic and therapeutic options of acquired liver injury and failure. This review provides a structured approach for the evaluation and treatment of acquired liver injury and failure in critically ill patients.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent causes of chronic liver disease. Currently, therapeutic options for NAFLD patients are limited, but new pharmacologic agents are being investigated in the course of clinical trials. Because most of these studies are focusing on patients with fibrosis stages II and III (according to Kleiner), non-invasive identification of patients with intermediate fibrosis stages (II and III) is of increasing interest.Evaluation of NAFLD Fibrosis Score (NFS) and liver stiffness measurement (LSM) for prediction of fibrosis stages II/III.Patients with histologically confirmed NAFLD diagnosis were included in the study. All patients underwent a clinical and laboratory examination as well as a LSM prior to liver biopsy. Predictive value of NFS and LSM with respect to identification of fibrosis stages II/III was assessed.134 NAFLD patients were included and analyzed. Median age was 53 (IQR 36 - 60) years, 55 patients (41 %) were female. 82 % of our patients were overweight/obese with typical aspects of metabolic syndrome. 84 patients (66 %) had liver fibrosis, 42 (50 %) advanced fibrosis. LSM and NFS correlated with fibrosis stage (r = 0.696 and r = 0.685, respectively; p 0.01 for both). NFS values between -2.0 and + 0.5, and LSM values between 8 and 22kPa were associated with fibrosis stages II/III. If both criteria were met, probability of fibrosis stage II/III was 61 %. If none of the two criteria was met, chance for fibrosis stage II/III was only 6 % (negative predictive value 94 %).Combination of LSM and NFS enables identification of patients with significant probability of fibrosis stage II/III. Accordingly, these tests, especially in combination, may be a suitable screening tool for fibrosis stages II/III in NAFLD. The use of these non-invasive methods might also help to avoid unnecessary biopsies.Die nicht-alkoholische Fettlebererkrankung (NAFLD) gehört mittlerweile weltweit zu den häufigsten Ursachen für eine chronische Leberschädigung. Aktuell sind die therapeutischen Optionen limitiert und neue pharmakologische Therapieoptionen werden primär im Rahmen von Studien untersucht. Da viele aktuelle Studien zumeist auf NAFLD-Patienten mit den Fibrosestadien II und III (nach Kleiner) abzielen, ist die nicht-invasive Identifikation dieser Patienten von zunehmender Bedeutung. ZIEL: Evaluation von Lebersteifigkeitsmessung (LSM) und NAFLD Fibrosis Score (NFS) im Hinblick auf die Vorhersage eines Fibrosestadiums II/III.Patienten mit bioptisch gesicherter NAFLD Diagnose wurden in die Studie eingeschlossen. Vor der Leberbiopsie wurden alle Patienten klinisch, laborchemisch und mittels LSM evaluiert. Anschließend wurde die Vorhersagekraft von NFS und LSM im Hinblick auf das Vorliegen einer Fibrose Stadium II/III untersucht.134 NALFD-Patienten wurden in die Studie eingeschlossen und untersucht. Das mittlere Alter betrug 53 (IQR 36 – 60) Jahre, 55 Patienten (41 %) waren weiblich. 82 % der Patienten waren übergewichtig/adipös mit typischen Befundkonstellationen des Metabolischen Syndroms. 84 Patienten (66 %) zeigten Zeichen einer Fibrose, bei 42 (50 %) bestand eine fortgeschrittene Fibrose. LSM und NFS korrelierten mit dem Fibrosestadium (r = 0,696 bzw. r = 0,685, p 0,01). NFS-Werte zwischen –2,0 und + 0,5 und LSM-Werte zwischen 8 und 22kPa waren mit hoher Wahrscheinlichkeit für das Vorliegen eines Fibrosestadiums II/III assoziiert. Wenn beide dieser Kriterien erfüllt waren, bestand zu 61 % ein Fibrosestadium II/II. Wenn hingegen keines der beiden Kriterien erfüllt war, lag die Wahrscheinlichkeit für eine Fibrose II/III lediglich bei 6 % (negativer prädiktiver Wert 94 %).Die Kombination von LSM und NFS ermöglicht die Identifikation von Patienten mit erhöhtem Risiko für ein Fibrosestadium II/III. Daher könnte der Einsatz dieser beiden nicht-invasiven Tests speziell in Kombination als Screening-Tool für NAFLD-Patienten im Hinblick auf das Vorhandensein einer Fibrose II/III eingesetzt werden. Durch den Einsatz dieser Verfahren könnten außerdem nicht-notwendige Biopsien vermieden werden.

BACKGROUND Acute-on-chronic liver failure (ACLF) is a severe complication of liver cirrhosis associated with excess short-term mortality rates. Orthotopic liver transplantation (OLT) is a potentially life-saving therapeutic modality for acute-on-chronic liver failure patients, but selection of transplant candidates with an acceptable post-transplant outcome is difficult. AIM To assess the risk of liver transplantation in patients with ACLF, and to determine parameters that predict post-transplant survival in this patient cohort. METHODS We retrospectively analysed all 250 patients with cirrhosis who underwent their first liver transplantation between 2009 and 2014 at our institution, and assessed post-transplant outcomes. RESULTS Of 250 cirrhotic liver transplant recipients, 98 patients fulfilled the diagnostic criteria for acute-on-chronic liver failure in the 3-month pre-transplant period. Compared to non-ACLF patients, ACLF was associated with significantly higher short-term morbidity and mortality after liver transplantation (90-day patient survival 96.1% non-ACLF vs 72.4% ACLF patients, P < 0.0001). Clinical improvement in the pre-transplant period, as defined by recovery of at least one previously failed organ system, was observed in 37 of 98 acute-on-chronic liver failure patients, mostly within several days after diagnosis. Most notably, clinical improvement prior to liver transplantation was associated with excellent post-transplant survival rates that approximated non-ACLF transplant recipients. Following the 90-day post-transplant period, patient survival and long-term graft functions were comparable between ACLF and non-ACLF liver transplant recipients for up to 5 years. CONCLUSIONS Acute-on-chronic liver failure predicts adverse outcome after orthotopic liver transplantation. Given the dismal prognosis without transplantation, however, our results indicate that ACLF patients can be transplanted with comparably good outcomes, in particular patients who improve under conservative therapeutic measures.

Background Jaundice and cholestatic hepatic dysfunction are frequent findings in critically ill patients associated with increased mortality. Cholestasis in critically ill patients is closely associated with stimulation of pro-inflammatory cytokines resulting in impaired bile secretion and subsequent accumulation of bile acids. Aim of this study was to evaluate the clinical role of circulating bile acids in critically ill patients. Methods Total and individual serum bile acids were assessed via high-performance liquid chromatography in 320 critically ill patients and 19 controls. Results Total serum bile acids were threefold higher in septic than cardiogenic shock patients and sixfold higher than in post-surgical patients or controls (p

Background Acid–base disturbances are frequently observed in critically ill patients at the intensive care unit. To our knowledge, the acid–base profile of patients with acute-on-chronic liver failure (ACLF) has not been evaluated and compared to critically ill patients without acute or chronic liver disease. Results One hundred and seventy-eight critically ill patients with liver cirrhosis were compared to 178 matched controls in this post hoc analysis of prospectively collected data. Patients with and without liver cirrhosis showed hyperchloremic acidosis and coexisting hypoalbuminemic alkalosis. Cirrhotic patients, especially those with ACLF, showed a marked net metabolic acidosis owing to increased lactate and unmeasured anions. This metabolic acidosis was partly antagonized by associated respiratory alkalosis, yet with progression to ACLF resulted in acidemia, which was present in 62% of patients with ACLF grade III compared to 19% in cirrhosis patients without ACLF. Acidemia and metabolic acidosis were associated with 28-day mortality in cirrhosis. Patients with pH values

Hypoxic hepatitis (HH) is a frequent and life-threatening complication associated with states of oxygen depletion in critically ill patients. Ischemia and reperfusion contribute to liver injury in HH. Experimental data suggest beneficial effects of statins in hepatic ischemia/reperfusion injury. This study was conducted to investigate whether statin treatment prior to intensive care unit (ICU) admission affects incidence rates and severity of HH.Eight hundred fifty-one patients admitted consecutively to three medical ICUs between December 2008 and December 2009 were prospectively screened for new occurrence of HH within 48 h following ICU admission. Statin treatment prior to ICU admission was assessed. 28-day-, 90-day-, and 1-year-survival as well as new-onset of complications in HH patients were prospectively documented.Eighty-seven patients (10%) developed HH. Statin treatment prior to ICU admission was significantly associated with decreased incidence of HH within 48 h after ICU admission in the multivariate analysis (adjusted OR=0.42 (95% CI 0.19-0.95); p0.05). Cardiogenic shock (p0.001), septic shock (p0.001) and active alcohol consumption (p0.01) were identified as independent risk factors for development of HH. 28-day-, 90-day-, and 1-year-mortality rates in HH were 58%, 67%, and 74%, respectively. Statins were associated with improved 28-day-survival in the total study cohort (p0.05), but did not affect 90-day- and 1-year-mortality, respectively.Cardiogenic shock, septic shock, and active alcohol consumption were independent factors predisposing patients to new onset of HH. Statin treatment prior to ICU admission was the only protective factor regarding the new occurrence of HH in critically ill patients.

Leberfunktionsstorungen konnen haufig bei kritisch kranken Patienten auf der Intensivstation (ICU) beobachtet werden und haben eine hohe Morbiditat und Mortalitat zur Folge. Die haufigsten Formen der Leberfunktionsstorung an der ICU sind die Schockleber und die cholestatische Leberfunktionsstorung mit Inzidenzraten bis zu 10 % bzw. 30 %. Beide Erkrankungen treten haufig als Folge einer Ischamie/Hypoxie meist im Rahmen eines kardiogenen Schocks, einer Sepsis oder eines septischen Schocks auf. Speziell im Fall der cholestatischen Leberdysfunktion wurden jedoch auch andere potenzielle Verursacher identifiziert. Dazu gehoren neben zugrunde liegenden Krankheiten, wie chronische Lebererkrankungen oder Malignome, auch iatrogene Faktoren, wie z. B. parenterale Ernahrung, hohe Beatmungsdrucke, chirurgische Eingriffe, verschiedene Medikamente und Bluttransfusionen. Fruhzeitiges Erkennen und Behandeln der zugrunde liegenden Ursache stellen bislang die einzigen etablierten Therapiemasnahmen bei Schockleber und cholestatischer Leberfunktionsstorung dar.

Acute and acute-on-chronic liver failure are often associated with development of organ failure. Its occurrence is associated with high morbidity and mortality. Extracorporeal replacement therapies are frequently necessary in these patient populations. Replacement therapies can be divided into renal replacement therapies and liver support therapies. These therapies consist of artificial liver support systems (i.e., MARS(®) system, Prometheus(®)), which are able to remove water-soluble and albumin-bound toxins, and of bioartifical liver support systems. This manuscript provides a review of current practice in the extracorporeal support of patients with liver diseases in the intensive care unit.

Wechselwirkungen zwischen dem kardiopulmonalen Kreislauf und der Leber sind bei Patienten mit portaler Hypertension sowie Leberzirrhose haufige Komplikationen. Von wesentlicher Bedeutung sind hierbei das hepatopulmonale Syndrom (HPS), die portopulmonale Hypertension (POPH) sowie der hepatische Hydrothorax. Das HPS tritt bei bis zu 30 % der Patienten mit Leberzirrhose auf und geht mit einer mehr als 2-fach gesteigerten Mortalitat einher. Das HPS sollte fruhzeitig mittels arterieller Blutgasanalyse und Kontrastmittelechokardiographie diagnostiziert werden, wahrend die POPH, eine Form der pulmonalarteriellen Hypertonie in Zusammenhang mit portaler Hypertension, letztendlich in der Rechtsherzkatheteruntersuchung festgestellt wird. Therapeutische Moglichkeiten sind eine Langzeitsauerstofftherapie und die orthotope Lebertransplantation fur das schwere HPS. Bei der POPH ist v. a. eine medikamentose Therapie mit Vasodilatoren, wie Prostazyklinen, Endothelinrezeptorantagonisten und Phosphodiesterase-5-Hemmern indiziert. In der folgenden Ubersicht werden die erwahnten Krankheitsbilder dargestellt, wobei ein Schwerpunkt auf das HPS gelegt wird.

Ganciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.

Hypoxic hepatitis is a common cause of hepatic impairment in critically ill patients and is an independent risk factor for mortality. An elevated level of unmeasured anions is another unfavourable prognostic marker in many disease entities. While the biochemical nature of unmeasured anions is unknown, data suggest that they may be released from the liver. Therefore, the purpose of this study was to determine whether the strong ion gap—the gold standard for estimation of unmeasured anions—is elevated and associated with outcome in patients with hypoxic hepatitis. One hundred and five consecutive patients with hypoxic hepatitis admitted to the (intensive care unit) ICU of a university hospital were prospectively included in the study and compared with 15 healthy controls. Compared with the controls, patients with hypoxic hepatitis had an elevated strong ion gap (4.0 ± 2.6 vs. 7.8 ± 4.0 mmol/L; p = 0.0002) that contributed to metabolic acidosis. Patients dying within 5 days had a larger strong ion gap upon admission than did patients surviving beyond 5 days. The mean strong ion gap (SIG) over the course of the first 5 days after admission to the ICU was 1.3 mmol/L (0.3–2.3 mmol/L) larger in patients who died compared with patients who survived, p = 0.008. In multivariate Cox-regression, larger strong ion gaps were associated with shorter survival time. The SIG correlated positively with both AST and ALT. Unmeasured anions are elevated in patients with hypoxic hepatitis, contribute to metabolic acidosis and are associated with mortality. The liver is a possible source of the unmeasured anions, which may represent markers of tissue damage in hypoxic hepatitis.

Einleitung: Veranderungen der Hamostase finden sich haufig bei Patienten mit Leberzirrhose. Der „disseminated intravascular coagulation score“ (DIC score) errechnet sich aus Routine-Gerinnungsparametern (Thrombozytenzahl, D-Dimere, Fibrinogen und Prothrombinzeit/-index) und ist ein bekannter Uberlebenspradiktor bei kritisch kranken Patienten. Aufgrund der Haufigkeit von „pathologischen“ Gerinnungsparametern bei Patienten mit Leberzirrhose ist bislang jedoch unklar, ob der DIC score eine prognostische Aussagekraft bei diesen Patienten besitzt. Ziele: Ziel dieser Studie ist die Bestimmung und die Beurteilung der Anwendbarkeit des DIC Score bei kritisch kranken Patienten mit Leberzirrhose. Methodik: Zirrhose-Patienten, die an der Intensivstation zur Aufnahme gelangten, wurden in dieser Arbeit analysiert. Detaillierte Laboruntersuchungen inklusive Gerinnungsanalysen wurden bei Aufnahme durchgefuhrt und der DIC Score berechnet. Das 28-Tage-Uberleben der Patienten wurde erhoben. Ergebnis: Hundertfunfzig Intensivstations-Aufnahmen mit Leberzirrhose wurden analysiert. Neununddreisig Prozent waren weiblich. Das mediane Alter betrug 56 (IQR 49 – 63) Jahre. Der mediane SOFA Score bei Aufnahme betrug 9 (6 – 13), der mediane MELD score 26 (IQR 18 – 36). Die 28-Tage-Mortalitat lag bei 59%. Der mediane DIC score bei Aufnahme betrug 5 (IQR 4 – 6). „Overt DIC“ (DIC Score ≥5) fand sich bei 65% der Aufnahmen. Bezogen auf die 28-Tage-Mortalitat war der DIC Score bei Nicht-Uberlebenden signifikant hoher als bei Uberlebenden (5 (IQR 4 – 7) vs. 4 (IQR 3 – 6); p < 0.01). Die AUROC fur den DIC Score hinsichtlich der Vorhersage der 28-Tage-Mortalitat war 0.68 (95% CI 0.59 – 0.77). Das Vorhandensein einer „Overt DIC“ bei Aufnahme war signifikant mit der 28-Tage-Mortalitat assoziiert (OR = 3.4 (95% CI 1.69 – 6.84), p < 0.01). Die 28-Tage-Mortalitatsrate bei Aufnahmen mit Zirrhose und „Overt DIC“ betrug 70% verglichen zu 40% bei Patienten mit einem DIC score < 5. Schlussfolgerung: Veranderungen der Hamostase finden sich in der Mehrzahl der Patienten mit Leberzirrhose auf der Intensivstation. Der DIC score ist ein Pradiktor fur das 28-Tage-Uberleben bei kritisch kranken Patienten mit Leberzirrhose.