Pulmonary impairment independently determines mortality in critically ill patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Diagnostic and prognostic significance of cell death markers in patients with cirrhosis and acute decompensation.

BACKGROUND: The transition from compensated to decompensated liver cirrhosis is a hallmark of disease progression, however, reliable predictors to assess the risk of decompensation in individual patients from routine diagnostics are lacking. Here, we characterize serum levels of cell death-associated markers and routine biochemistry from patients with chronic liver disease with and without decompensation. METHODS: A post-hoc analysis was based on prospectively collected clinical data from 160 patients with chronic liver disease, stably compensated or decompensated at baseline or during follow-up, over a median period of 721 days. Serum levels of damage-associated molecular patterns (DAMPs) and routine biochemistry are quantified at baseline (for all patients) and during follow-up (for patients with acute decompensation). The panel of DAMPs assessed in this study comprises high-mobility group-box protein 1 (HMGB1), cytochrome C (cyt C), soluble Fas-ligand (sFasL), interleukin 6 (IL-6), soluble cytokeratin-18 (CK18-M65) and its caspase-cleaved fragment CK18-M30. RESULTS: In this cohort study, 80 patients (50%) were diagnosed with alcoholic liver cirrhosis, 60 patients (37.5%) with hepatitis C virus- and 20 patients (13.5%) with hepatitis B virus-related liver cirrhosis. At baseline, 17 patients (10.6%) showed decompensated liver disease and another 28 patients (17.5%) developed acute decompensation during follow-up (within 24 months). One hundred fifteen patients showed stable liver disease (71.9%). We found DAMPs significantly elevated in patients with decompensated liver disease versus compensated liver disease. Patients with acute decompensation during follow-up showed higher baseline levels of IL-6, sFasL, CK18-M65 and-M30 (P<0.01) compared to patients with stably compensated liver disease. In multivariate analyses, we found an independent association of baseline serum levels of sFasL (P = 0.02; OR = 2.67) and gamma-glutamyl transferase (GGT) (P<0.001; OR = 2.1) with acute decompensation. Accuracy of the marker combination for predicting acute decompensation was high (AUC = 0.79). Elevated aminotransferase levels did not correlate with decompensated liver disease and acute decompensation. CONCLUSIONS: DAMPs are elevated in patients with decompensated liver disease and patients developing acute decompensation. The prognostic value of a marker combination with soluble Fas-ligand and GGT in patients with liver cirrhosis should be further evaluated.

Transabdominal ultrasonography to reduce the burden of X-ray imaging in prophylactic pancreatic stent localization after ERCP-A prospective trial.

BACKGROUND: Before performing endoscopy to remove prophylactic pancreatic stents placed in patients with high risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), X-ray imaging is recommended to confirm the stents position in the pancreatic duct. OBJECTIVES: The aim of the present study was to investigate the feasibility of prophylactic pancreatic stent detection by transabdominal ultrasonography, to reduce the burden of X-ray imaging, which is currently the golden standard. METHODS: All patients who received a pancreatic stent for PEP prophylaxis were included in the present prospective trial. First, stent position was determined by transabdominal ultrasonography. Afterwards, it was verified by X-ray imaging. Retained stents were removed by esophagogastroduodenoscopy. Dislocated stents needed no further intervention. RESULTS: Fourty-one patients were enrolled in this study. All prophylactic pancreatic stents were straight 6 cm long 5 Fr stents with external flap. All stents were removed between day 1 and 10 (median: 3 days) in all cases. In 34 of 41 cases (83.0%), the pancreatic stent was still in place on the day of examination. Twenty-nine of 34 (85.3%) stents were detected correctly by transabdominal ultrasonography. Overlying gas prevented visualization of the pancreas in 3/41 (7.3%) cases. Sensitivity of sonographic detection of the stent was 93.5% (29/31). Six of seven stents were determined correctly as dislocated by ultrasonography. Here, specificity was 85.7%. A positive predictive value of 96.7% (29/30) was examined. The negative predictive value was 75.0% (6/8). CONCLUSION: Transabdominal ultrasonography detects the majority of prophylactic pancreatic stents. Thereby, it helps to identify patients with an indication for endoscopy sufficiently. X-ray imaging could subsequently be omitted in about 70% of examinations, reducing the radiation exposure for the patient and the endoscopy staff.

Hepatitis C Clearance by Direct-Acting Antivirals Impacts Glucose and Lipid Homeostasis.

BACKGROUND: Chronic hepatitis C virus (HCV) infections are causally linked with metabolic comorbidities such as insulin resistance, hepatic steatosis, and dyslipidemia. However, the clinical impact of HCV eradication achieved by direct-acting antivirals (DAAs) on glucose and lipid homeostasis is still controversial. The study aimed to prospectively investigate whether antiviral therapy of HCV with DAAs alters glucose and lipid parameters. METHODS: 50 patients with chronic HCV who were treated with DAAs were screened, and 49 were enrolled in the study. Biochemical and virological data, as well as noninvasive liver fibrosis parameters, were prospectively collected at baseline, at the end of treatment (EOT) and 12 and 24 weeks post-treatment. RESULTS: 45 of 46 patients achieved sustained virologic response (SVR). The prevalence of insulin resistance (HOMA-IR) after HCV clearance was significantly lower, compared to baseline (5.3 ± 6.1 to 2.5 ± 1.9, p < 0.001), which is primarily attributable to a significant decrease of fasting insulin levels (18.9 ± 17.3 to 11.7 ± 8.7; p = 0.002). In contrast to that, HCV eradication resulted in a significant increase in cholesterol levels (total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein (HDL-C) levels) and Controlled Attenuated Score (CAP), although BMI did not significantly change over time (p = 0.95). Moreover, HOMA-IR correlated significantly with noninvasive liver fibrosis measurements at baseline und during follow-up (TE: r = 0.45; p = 0.003, pSWE: r = 0.35; p = 0.02, APRI: r = 0.44; p = 0.003, FIB-4: r = 0.41; p < 0.001). CONCLUSION: Viral eradication following DAA therapy may have beneficial effects on glucose homeostasis, whereas lipid profile seems to be worsened.