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Background & Aims: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections.
Methods: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study).
Results: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines.
Conclusions: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.
Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients.
Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine<1.5, no HE, no OF; AD-2: creatinine 1.5–2, and or HE grade I/II, no OF; AD-3: Creatinine<1.5, no HE, non-renal OF).
Results: Most markers were slightly abnormal in compensated cirrhosis, but markedly increased in AD. Patients with ACLF exhibited the largest number of abnormal markers, indicating “full-blown” systemic inflammation (all markers). AD-patients exhibited distinct systemic inflammation profiles across three different clinical phenotypes. In each phenotype, activation of systemic inflammation was only partial (30% of the markers). Mortality related to each clinical AD-phenotype was significantly lower than mortality associated with ACLF (p < 0.0001 by gray test). Among AD-patients baseline systemic inflammation (especially IL-8, IL-6, IL-1ra, HNA2 independently associated) was more intense in those who had poor 28-day outcomes (ACLF, death) than those who did not experience these outcomes.
Conclusions: Although AD-patients exhibit distinct profiles of systemic inflammation depending on their clinical phenotypes, all these patients have only partial activation of systemic inflammation. However, those with the most extended baseline systemic inflammation had the highest the risk of ACLF development and death.
Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.
Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.
Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA.
Conclusion: This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.
Lay summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.