Patients with cirrhosis are susceptible to develop infections because of immune dysfunction, changes in microbiome and increase in bacterial translocation from the gut to systemic circulation. ...Bacterial infections can worse the clinical course of the disease, triggering the development of complications such as acute kidney injury, hepatic encephalopathy, organ failures and acute on chronic liver failure. In recent years, the spread of multi drug resistant bacteria made more challenging the management of infections in patients with cirrhosis. Hence, the mortality rate associated to sepsis is increasing in these patients. Therefore, the optimization of the management of infections has a high priority in cirrhosis. Herein we reviewed the recent changes in the epidemiology and the management of bacterial infections in patients with liver cirrhosis.
Abstract
Bacterial infections are the most common trigger of acute decompensation of cirrhosis. The occurrence of infections in cirrhosis is associated with the development of organ dysfunctions, ...failures, and acute on chronic liver failure. The combination of infections and organ dysfunction/acute on chronic liver failure dramatically increases the mortality risk in these patients. Infections in cirrhosis are a big challenge for clinicians, since the mortality from sepsis is increasing in these patients worldwide. The rapid and progressive spread of multiresistant bacteria has been blamed for the increased mortality rate. Several studies have shown that early diagnosis and appropriate administration of antibiotic treatment are crucial for improving prognosis in these patients. Moreover, the prevention and treatment of acute kidney injury and organ failures are fundamental parts of management of infections in cirrhosis. Herein we provided a concise and updated review of the literature on bacterial infections in patients with cirrhosis.
While ascites is the most frequent first decompensating event in cirrhosis, the clinical course after ascites as the single index decompensation is not well defined. The aim of this multicentre study ...was thus, to systematically investigate the incidence and type of further decompensation after ascites as the first decompensating event and to assess risk factors for mortality.
622 cirrhotic patients presenting with grade-2/-3 ascites as the single index decompensating event at two university hospitals (Padova/Vienna) between 2003-2021 were included. Events of further decompensation, liver transplantation and death were recorded.
Mean age was 57±11years, most patients were male (n=423,68%) with alcohol-related (n=366,59%) and viral (n=200,32%) liver disease as the main etiologies. 323(52%) patients presented with grade-2 and 299(48%) with grade-3 ascites. Median Child-Pugh score at presentation was 8(IQR:7-10) and mean MELD was 15±6.
During a median follow-up period of 49 months, 350(56%) patients experienced further decompensation: refractory ascites (n=130,21%), hepatic encephalopathy (n=112,18%), SBP (n=32,5%), HRS-AKI (n=29,5%). Variceal bleeding as an isolated further decompensation event was rare (n=18,3%), while non-bleeding further decompensation (n=161,26%) and ≥2 concomitant further decompensation events (n=171,27%) were frequent. TIPS was used in only 81(13%) patients.
In patients presenting with grade-2 ascites, MELD≥15 indicated a considerable risk for further decompensation (SHR:2.18;p<0.001; 1-year-incidences:<10:10%vs.10-14:13%vs.≥15:28%) and of mortality (SHR:1.89;p=0.004; 1-year-incidences:<10:3%vs.10-14:6%vs.≥15:14%). Importantly, mortality was similarly high throughout MELD-strata in grade-3 ascites (p=n.s. for different MELD-strata; 1-year-incidences:<10:14%vs.10-14:15%vs.≥15:20%).
Further decompensation is frequent in patients with ascites as a single index decompensation event and only rarely due to bleeding. While patients with grade-2 ascites and MELD<15 seem to have a favourable prognosis, grade-3 ascites indicates high risk for mortality across all MELD-strata.
Studies on the clinical course of cirrhotic patients with first single ascites decompensation are scarce. However, many studies have shown the clinical implications of ascites graduation for risk prediction/stratification. Since the treatment paradigm in decompensated advanced chronic liver disease shifted towards prevention of further decompensation and mortality next to treating/controlling ascites, studies on first/further decompensation in patients with fist single ascites decompensation are needed. Our study demonstrates, on the one hand, that further decompensation/mortality is common in patients with presenting with single grade-3 ascites as index decompensation, yet on the other hand, unrelated to MELD stratification. In patients with single grade-2 ascites index decompensation MELD score can discriminate patients with favourable/poor outcome.
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•Course of patients with first single ascites decompensation has so far not been described yet.•MELD score is important for risk prediction/stratification in patients with grade-2 ascites but has no implications in patients with grade-3 ascites and first single ascites decompensation.•A threshold of MELD 15 points discriminates patients with favourable/poor outcome in patients with grade-2 ascites.•In patients with grade-3 ascites, regardless of MELD, treatment strategies should be intensified.
Ascites is the most common complication of cirrhosis, with 5-year mortality reaching 30%. Complications of ascites (ie, spontaneous bacterial peritonitis, hepatorenal syndrome, recurrent/refractory ...ascites, and hepatic hydrothorax) further worsen survival. The development of ascites is driven by portal hypertension, systemic inflammation, and splanchnic arterial vasodilation. Etiologic treatment and nonselective beta-blockers can prevent ascites in compensated cirrhosis. The treatment of ascites is currently based on the management of fluid overload (eg, diuretics, sodium restriction, and/or paracenteses). In selected patients, long-term albumin use, norfloxacin prophylaxis, and transjugular intrahepatic portosystemic shunt reduce the risk of further decompensation and improve survival.
Bacterial infections are frequent in patients with cirrhosis and increase the risk of death and drop-out from liver transplant (LT) waiting list. In patients with bacterial infections, LT is ...frequently delayed because of the fear of poor outcomes. We evaluated the impact of pre-LT infections on post-LT complications and survival.
From 2012 to 2018, consecutive patients transplanted at the Hospital of Padua were identified and classified in two groups: patients surviving an episode of bacterial infection within 3 months before LT (study group) and patients without infections before LT (control group). Post-LT outcomes (complications, new infections, survival) were collected.
A total of 466 LT recipients were identified (study group n = 108; control group n = 358). After LT, the study group had a higher incidence of new bacterial (57% vs. 20%, p <0.001) and fungal infections (14% vs. 5%, p = 0.001) and of septic shock (8% vs. 2%, p = 0.004) than the control group. Along with the model for end-stage liver disease (MELD) score and alcohol-related cirrhosis, bacterial infection pre-LT was an independent predictor of post-LT infections (odds ratio = 3.92; p <0.001). Nevertheless, no significant difference was found in 1-year (88% vs. 89%, p = 0.579) and 5-year survival rates (76% vs. 75%, p = 0.829) between the study group and control group. Within the study group, no association was found between the time elapsed from infection improvement/resolution to LT and post-LT outcomes.
Patients with pre-LT infections have a higher risk of new bacterial and fungal infections and of septic shock after LT. However, post-LT survival is excellent. Therefore, as soon as the bacterial infection is improving/resolving, transplant should not be delayed, but patients with pre-transplant bacterial infections require active surveillance for infections after LT.
Bacterial infections increase mortality and delay transplant in patients with cirrhosis awaiting liver transplantation (LT). Little is known about the impact of adequately treated infections before LT on post-transplant complications and outcomes. The study highlights that pre-LT infections increase the risk of post-LT infections, but post-LT survival rates are excellent despite the risk. These findings suggest that physicians should not delay LT because of concerns about pre-LT infections, but instead should actively monitor these patients for infections after surgery.
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•In patients with cirrhosis, the prognostic impact of pre-LT infections is not completely understood.•Pre-LT infections increase the risk of post-LT infections but do not affect patients’ survival.•Time from infection resolution to LT does not affect incidence of post-LT complication and survival rates.•As soon as infections are resolving, it is safe to proceed with LT without any delay.•Patients with pre-LT infection require active surveillance for infections after LT.
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