Systemic inflammation in decompensated cirrhosis: Characterization and role in acute‐on‐chronic liver failure

TLDR

ACLF in cirrhosis presents with acute decompensation, organ failure, and high short‑term mortality. The study tests the hypothesis that ACLF arises from an acute exacerbation of systemic inflammation already present in decompensated cirrhosis. The authors measured 29 cytokines, albumin redox state (HNA2), plasma renin, and copeptin in 522 decompensated cirrhosis patients (237 with ACLF) and 40 healthy controls, with baseline and serial assessments during hospitalization. Patients with ACLF showed markedly higher systemic inflammation and oxidative stress than those with decompensation alone, and the severity of inflammation correlated with ACLF severity, mortality, and was a stronger predictor than circulatory dysfunction. Hepatology 2016;64:1249‑1264.

Abstract

Acute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short-term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI was assessed by measuring 29 cytokines and the redox state of circulating albumin (HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction (SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations. Measurements were performed at enrollment (baseline) in all patients and sequentially during hospitalization in 255. The main findings of this study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed significantly higher levels of these markers than those without ACLF; (2) different cytokine profiles were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial infection, and others); (3) severity of SI and frequency and severity of ACLF at enrollment were strongly associated. The course of SI and the course of ACLF (improvement, no change, or worsening) during hospitalization and short-term mortality were also strongly associated; and (4) the strength of association of ACLF with SI was higher than with SCD. Conclusion: These data support SI as the primary driver of ACLF in cirrhosis. (Hepatology 2016;64:1249-1264).