End-stage liver disease: the hidden immunosuppressive condition. From an epidemiological update to therapeutic management models

The objective of this work was to describe the current epidemiology, evaluate the short and long-term prognosis and test novel strategies to treat infections in cirrhotic patients Methods We conducted four studies using two different cohort of cirrhotic patients collected prospectively and developing bloodstream infections (BSIs) at 19 centers from September-2014 to December-2015 (BICHROME) and all consecutive cirrhotic patients admitted for an episode of acute decompensation from January-2014 to March-2016 at S.Orsola-Malpighi Hospital, Bologna and at the “Infermi” Hospital, Rimini(BIC). Results The BICHROME study included 312 patients. Gram-negative bacteria, Gram-positive cocci (GPC) and Candida spp. caused 53%, 47% and 7% of episodes, respectively. At multivariate analysis factors independently associated to GPC isolation were alcoholic cirrhosis (p=0.03), device-related infection (p=0.007), pneumonia (p=0.02), previous hepatorenal syndrome (p=0.03) and diabetes with organ damage (p=0.008) The 30-day mortality rate was 25% and best predicted by the CLIF-SOFA score (aROC 0.82). In a Cox-regression model, delayed (>24h) antibiotic treatment (p<0.001), inadequate empirical therapy(p<0.001) and CLIF-SOFA(p<0.001) were predictors of 30-day mortality. Among patients receiving adequate treatment with piperacillin-tazobactam or carbapenems, those receiving continuous or extended infusion of such antibiotics showed a significantly lower mortality rate even after adjusting for cofounding factors(p=0.04). In the BIC study, among the 516 patients enrolled, 32% presented an infection. Multivariate logistic regression showed that MELD-Na (p=0.001), QuickSOFA (p=0.004), bacteremia (p=0.004) and isolation MDR pathogens (p=0.048) were independent predictors of acute-on-chronic liver failure(ACLF). Kaplan-Meyers curves showed that 1-year survival was similar in infected and non-infected patients without ACLF (71% vs 67%,p=0.337). As expected, 1-year survival was worsened by the presence of ACLF. Conclusion With this work we explored the current epidemiology of bacterial infection in cirrhotic patients, we identified risk factors for MDR pathogens and for BSI caused by GPC. We also assessed long-term prognosis of infection complicated or non-complicated by ACLF.