Background & Aims Single nucleotide polymorphisms (SNPs) in IL28B and serum levels of interferon γ inducible protein 10 (IP-10) predict outcomes of antiviral therapy in patients with chronic ...hepatitis C. We associated IL28B SNPs rs12979860 and rs8099917, along with serum levels of IP-10, with outcomes of patients with acute hepatitis C (AHC). Methods We studied 120 patients with AHC (64 male; 37 ± 16 years old) and 96 healthy individuals (controls). The IL28B SNPs rs12979860 and rs8099917 were detected using real-time polymerase chain reaction; serum concentrations of IP-10 were measured by enzyme-linked immunosorbent assays of 62 patients with AHC. Results Hepatitis C virus was cleared spontaneously from 59 patients (49.2%). The IL28B rs12979860 C/C genotype was more frequent among patients with AHC than controls (62.5% vs 39.6%; P < .001) and among patients with spontaneous clearance than those without (74.6% vs 51.7%; P = .02) (positive predictive value, 60.3%). Patients with IL28B rs12979860 C/C more frequently developed jaundice (53.2% vs 27.6%; P = .022) than carriers of the T allele. The median level of IP-10 was lower among patients with AHC and spontaneous clearance (764 113–2470 pg/mL) than those without spontaneous clearance (1481 141–4412 pg/mL; P = .006). Based on receiver operating characteristic analysis, 540 pg/mL IP-10 was set as the cutoff for patients most likely to have spontaneous clearance (positive predictive value, 71.4%; negative predictive value, 65.9%). Including data on IP-10 levels increased the ability of the IL28B rs12979860 C/C to identify patients most likely to have spontaneous clearance (83% of those who had an IP-10 level <540 pg/mL and 32% who had an IP-10 level >540 pg/mL) ( P < .01). Conclusions The combination of serum level of IP-10 and SNPs in IL28B can identify patients with AHC who are most likely to undergo spontaneous clearance and those in need of early antiviral therapy.
Monitoring of chronic Hepatitis C (CHC) treatment relies on HCV RNA quantification by means of real-time PCR methods. Assay specific analytical sensitivities may impact therapy management.
...Comparative analysis between three commercial assays (Roche COBAS AmpliPrep/COBAS TaqMan Version 1 (CAP/CTM Ver. 1), Version 2 (CAP/CTM Ver. 2) and the Abbott RealTime HCV (ART) assay) was performed on 247 available samples taken at key decision time points during antiviral therapy of 105 genotype 1 patients (triple therapy: n = 70; dual therapy: n = 35).
Overall concordance of HCV RNA measurements was high between the two Roche systems (89%; n = 220/247) but lower between the Roche assays and the ART (CAP/CTM Ver. 1 vs ART: 77.3%; n = 191/247 and CAP/CTM v.2 vs ART: 80.1%; n = 198/247). Most discrepancies were noted in week 4/8 samples with residual viremia (<LLOQ) detected by ART (<LLOQ: n = 45, 44.1%) but undetectable HCV RNA by CAP/CTM Ver. 1 (<LLOQ: n = 18, 17.6%) or CAP/CTM Ver. 2 (<LLOQ: n = 26, 25.5%). Based on results by CAP/CTM Ver. 1, 13 eligible patients underwent an abbreviated course of therapy (24 weeks). Only 1 patient experienced virologic breakthrough. If tested by ART, only 6/13 patients (46.2%) would have been eligible for shortened treatment. Consequently, RGT guidelines were adapted and shortening of therapy was allowed if residual viremia was detected by ART at week 4/8.
An abbreviated course of treatment can safely be applied in patients with residual viremia (<LLOQ) detected by ART in samples collected at week 4/8 of treatment.
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
< 0.001). Elevated bile acid levels correlated with severity of illness, renal dysfunction and inflammation (
p
< 0.05). Total bile acids predicted 28-day mortality independently of sex, age, serum bilirubin and severity of illness (HR 1.041, 95% CI 1.013–1.071,
p
< 0.005). Best prediction of mortality of total bile acids was seen in patients suffering from septic shock.
Conclusions
Individual and total BAs are elevated by various degrees in different shock conditions. BAs represent an early predictor of short-term survival in a mixed cohort of ICU patients and may serve as marker for early risk stratification in critically ill patients. Future studies should elucidate whether modulation of BA metabolism and signalling influences the clinical course and outcome in critically ill patients.
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 < 7.1 showed a 100% mortality rate. Acidosis attributable to lactate and unmeasured anions was independently associated with mortality in liver cirrhosis.
Conclusions
Cirrhosis and especially ACLF are associated with metabolic acidosis and acidemia owing to lactate and unmeasured anions. Acidosis and acidemia, respectively, are associated with increased 28-day mortality in liver cirrhosis. Lactate and unmeasured anions are main contributors to metabolic imbalance in cirrhosis and ACLF.
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.
Lactate levels and lactate clearance are known predictors of outcome in critically ill patients in the intensive care unit (ICU). The prognostic value of lactate is not well established in liver ...cirrhosis and acute‐on‐chronic liver failure (ACLF). The aim of this study was to assess the prognostic value of lactate levels and clearance in critically ill patients with cirrhosis. Patients with cirrhosis admitted to the ICU were studied at the University Medical Center Hamburg‐Eppendorf (n = 566, derivation cohort) and the Medical University of Vienna and the University Hospitals Leuven (n = 250, validation cohort). Arterial lactate was measured on admission and during the first 24 hours. Patients were followed for 1 year and outcome was assessed. Admission lactate was directly related to the number of organs failing and to 28‐day mortality (area under receiver operating characteristic AUROC 0.72; P < 0.001). This also applied to lactate follow‐up measurements after 6, 12, and 24 hours (P < 0.001 for all, AUROC > 0.70 for all). Lactate clearance had significant predictive ability for 28‐day mortality in patients with elevated serum lactate ≥5 mmol/L. Admission lactate and 12‐hour lactate clearance (in patients with admission lactate ≥5 mmol/L), respectively, were identified as significant predictors of 1‐year mortality, independent of Chronic Liver Failure Consortium acute‐on‐chronic liver failure score (CLIF‐C ACLFs). A lactate‐adjusted CLIF‐C ACLFs was developed (CLIF‐C ACLFsLact), which performed significantly better than the original CLIF‐C ACLFs in prediction of 28‐day mortality in the derivation and validation cohort. Conclusion: Lactate levels appropriately reflect severity of disease and organ failure and were independently associated with short‐term mortality in critically ill patients with liver cirrhosis. Lactate is a simple but accurate prognostic marker, and its incorporation improved performance of CLIF‐C ACLFs significantly.
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 (P < 0.001 for all). Moreover, fibrinogen, platelets, and activated partial thromboplastin time (but not prothrombin index) differed significantly between cirrhosis patients with and without major bleeding (P < 0.01 for all). Bleeding on admission, platelet count <30 < 109/L, fibrinogen level <60 mg/dL, and activated partial thromboplastin time values >100 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 (P < 0.05 between groups). Conclusion: 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 & 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
One hundred and forty‐three patients with 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 and 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<.001) and correlated significantly with model of end‐stage liver disease (MELD) and hepatic venous pressure gradient (P<.001). Total BAs predicted new onset of AD or ACLF during follow‐up (OR 1.025, 95% CI: 1.012–1.038, P<.001). Best cut‐off predicting new onset of AD/ACLF and survival during course of time was total BAs ≥36.9 μmol/L.
Conclusions
Serum total and individual BAs are associated with AD and ACLF in patients with cirrhosis. Assessment of total BAs could serve as additional marker for risk stratification in cirrhotic patients with respect to new onset of AD and ACLF.
PDF
