The Value of Neutrophil-to-Lymphocyte Ratio to Identify Bacterial Infection and Predict Short-Term Mortality in Patients with Acutely Decompensated Cirrhosis.

Liver cirrhosis patients are highly susceptible to infections, affecting survival, but current parameters for detecting infection are not reliable enough in this population. We investigated the ability of white blood cell (WBC), ∆WBC, neutrophil and ∆neutrophil counts, neutrophil-to-lymphocyte (NLR) and ∆NLR ratios and C-reactive protein (CRP) and procalcitonin (PCT) levels to identify infection and predict short-term mortality in liver cirrhosis patients. We recruited 233 patients with liver cirrhosis hospitalized with acute decompensation (AD) who had an outpatient visit within 1 month (baseline laboratory data) and followed them for 90 days. Difference between laboratory values at baseline and the AD episode was defined as delta (∆) values of the parameters. Delta values did not increase the diagnostic and predictive ability of investigated parameters. The CRP level was found to be the best diagnostic marker for infection in patients with cirrhosis. However, NLR seems to be superior for short-term mortality prediction, better than the WBC count. Distinguishing inflammations of different origin is a remaining clinical challenge in acutely decompensated cirrhosis. Based on our results, NLR might be more suitable for predicting short-term mortality in patients with AD than the WBC count currently included in the CLIF-C AD score.

Increased sTREM-1 levels identify cirrhotic patients with bacterial infection and predict their 90-day mortality.

BACKGROUND AND AIMS: Patients with cirrhosis are susceptible to bacterial infections (BIs) that are major causes of specific complications and mortality. However, the diagnosis of BIs can often be difficult in advanced disease stage since their symptoms may overlap with the ones of acute decompensation (AD). Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from monocytes/macrophages and neutrophils during activation and has been reported to correlate with activity of various inflammatory processes. We investigated its diagnostic and prognostic performance in patients with cirrhosis and BI. METHODS: Sera of 269 patients were assayed for sTREM-1 by ELISA (172 outpatients and 97 patients with AD of whom 56 had BI). We investigated capacity of sTREM-1 to identify patients with BI and conducted a 90-day follow-up observational study to assess its possible association with short-term mortality. RESULTS: sTREM-1 levels were significantly higher in patients with more severe liver disease, BI, and acute-on-chronic liver failure than in patients without these conditions. sTREM-1 had similar accuracy to CRP identifying BI [sTREM-1: AUROC (95%CI) 0.804 (0.711-0.897), p < 0.0001; CRP: 0.791 (0.702-0.881), p < 0.0001)] among AD patients. The combination of these two molecules and the presence of ascites into a composite score significantly increased their discriminative power (AUROC: 0.878, 95%CI: 0.812-0.944, p < 0.0001). High sTREM-1 level (>660 pg/mL) was an independent predictor of 90-day mortality in patients with BI [HR: 2.941, (95%CI: 1.009-8.573), p = 0.048] in our multivariate model. CONCLUSIONS: Use of sTREM-1 could increase the recognition of BIs in cirrhosis and help clinicians in mortality risk assessment of these patients.

Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients: a cohort study.

BACKGROUND: Both iron overload and iron deficient anemia can associate with cirrhosis. At the same time, inflammation might be continuously present in cirrhotic patients due to bacterial translocation and patients' susceptibility to infections. Ferritin is a sensitive and widely available marker of iron homeostasis, in addition it acts as an acute phase protein. Therefore, we evaluated the prognostic potential of serum ferritin in the long-term follow-up of cirrhotic outpatients. METHODS: A cohort of 244 cirrhotic outpatients was recruited and followed for 2 years. We measured their serum ferritin levels in our routine laboratory unit at enrolment and investigated its association with clinical outcomes. RESULTS: Ferritin serum level was higher in males and older patients than in females (median: 152.6 vs. 75 µg/L, p < 0.001) or younger individuals (median: 142.9 vs. 67.9 µg/L, p = 0.002). Patients who previously survived variceal bleeding had lower ferritin levels (median: 43.1 vs. 146.6 µg/L, p < 0.001). In multivariate regression models, including laboratory and clinical factors, lower (< 40 µg/L) ferritin concentration was associated with the development of decompensated clinical stage in patients with previously compensated cirrhosis (sHR: 3.762, CI 1.616-8.760, p = 0.002), while higher (> 310 µg/L) circulating ferritin levels were associated with increased risks of bacterial infections in decompensated patients (sHR: 2.335, CI 1.193-4.568, p = 0.013) and mortality in the whole population (HR: 2.143, CI 1.174-3.910, p = 0.013). CONCLUSION: We demonstrated usefulness of serum ferritin as a prognostic biomarker in cirrhosis, pointing out that both low and high concentrations need attention in these patients.

LIFEStyle, Prevention and Risk of Acute PaNcreatitis (LIFESPAN): protocol of a multicentre and multinational observational case-control study.

INTRODUCTION: Acute pancreatitis (AP) is a life-threatening inflammatory disease of the exocrine pancreas which needs acute hospitalisation. Despite its importance, we have significant lack of knowledge whether the lifestyle factors elevate or decrease the risk of AP or influence the disease outcome. So far, no synthetising study has been carried out examining associations between socioeconomic factors, dietary habits, physical activity, chronic stress, sleep quality and AP. Accordingly, LIFESPAN identifies risk factors of acute pancreatitis and helps to prepare preventive recommendations for lifestyle elements. METHODS AND ANALYSIS: LIFESPAN is an observational, multicentre international case-control study. Participating subjects will create case and control groups. The study protocol was designed according to the SPIRIT guideline. Patients in the case group (n=1700) have suffered from AP (alcohol-induced, n=500; biliary, n=500; hypertriglyceridemiainduced, n=200; other, n=500); the control group subjects have no AP in their medical history. Our study will have three major control groups (n=2200): hospital-based (n=500), population-based (n=500) and aetiology-based (alcohol, n=500; biliary, n=500 and hypertriglyceridemia, n=200). All of them will be matched to the case group individually by gender, age and location of residence. Aggregately, 3900 subjects will be enrolled into the study. The study participants will complete a complex questionnaire with the help of a clinical research administrator/study nurse. Analysis methods include analysis of the continuous and categorical values. ETHICS AND DISSEMINATION: The study has obtained the relevant ethical approval (54175-2/2018/EKU) and also internationally registered (ISRCTN25940508). After obtaining the final conclusions, we will publish the data to the medical community and will also disseminate our results via open access. TRIAL REGISTRATION NUMBER: ISRCTN25940508; Pre-results.

Deleterious effect of proton pump inhibitors on the disease course of cirrhosis.

OBJECTIVES: Proton pump inhibitors(PPIs) are widely prescribed to patients with liver cirrhosis. We hypothesized that long-standing PPI use is associated with spontaneous bacterial peritonitis(SBP) and accelerated development of disease-specific complications and liver-related death. METHODS: A 5-year follow-up observational cohort study assessed the impact of long-standing PPI use on the clinical course of cirrhosis in a large referral patient cohort. Three hundred fifty patients with cirrhosis (alcohol:69.1%, Child-Pugh stage A/B/C:206/108/36) were assigned to two groups: regular PPI users (n=196) and nonusers (n=154). Occurrence of SBP, decompensation events (ascites, hepatic encephalopathy and variceal bleeding), and liver-related death were assessed. RESULTS: Regular PPI use was associated with an increased cumulative probability of SBP compared to nonusers [55% vs. 24.8%, hazard ratio(HR):4.25; P=0.05], in patients without previous SBP episode (n=84). A similar association was found between regular PPI use and decompensation events. The risk of the development of a first decompensation was higher in regular PPI users compared with nonusers, in patients with compensated clinical stage at enrollment (HR: 2.81, P= 0.008, n=146). The risk of liver-related death was also significantly increased among regular PPI users (P<0.001). In multivariate Cox-regression analysis, regular PPI use (HR:2.81, P=0.003) and MELD score (HR:1.21, P<0.001) was an independent predictor of mortality. CONCLUSION: In the present follow-up cohort study, long-term PPI use was associated with the development of SBP and a progressive disease course in patients with cirrhosis that may have been caused by enhanced pathologic bacterial translocation, accelerated development of bacterial translocation-dependent disease-specific complications, and liver-related death.