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.