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Systemic inflammation drives acute-on-chronic liver failure

Recent data published in Hepatology suggest systemic inflammation as the main driver of acute-on-chronic liver failure in patients with decompensated cirrhosis.

“The current study supports the systemic inflammation hypothesis of acute decompensation and acute-on-chronic liver failure in cirrhosis,” Joan Clària, MD, clinical biochemist in the Hospital Clinic of Barcelona, and colleagues wrote. “Acute decompensation occurs in the setting of very high plasma levels of cytokines and oxidized albumin. Acute-on-chronic liver failure develops when there is a further increase in these inflammatory mediators.”

Acute-on-chronic liver failure is characterized by acute decompensation, organ failure and increased short-term mortality, the researchers wrote.

To test whether acute-on-chronic liver failure is the expression of systemic inflammation already present in decompensated cirrhosis, the researchers studied 522 patients with cirrhosis and 40 controls. They assessed systemic inflammation at baseline and again at hospitalization by measuring 29 cytokines as well as the redox state of circulating albumin, a marker of systemic oxidative stress. They also used plasma renin and copeptin concentrations to estimate systemic circulatory dysfunction.

Researchers found that while patients with acute decompensation without acute-on-chronic liver failure had very high baseline levels of inflammatory cytokines, circulating albumin, plasma renin and copeptin, patients with acute-on-chronic liver failure had even higher levels. There was a different cytokine profile for each acute-on-chronic liver failure precipitating event, including alcoholism and bacterial infection. The severity of systemic inflammation was associated with the frequency and severity of acute-on-chronic liver failure. The course of systemic inflammation as well as acute-on-chronic liver failure were each associated with short-term mortality. Further, the strength of the association of acute-on-chronic liver failure with systemic inflammation was higher than with systemic circulatory dysfunction.

The researchers concluded that their data support systemic inflammation as the primary driver of acute-on-chronic liver failure in patients with cirrhosis.

“Severity of systemic inflammation at enrollment and progression or regression of systemic inflammation during hospitalization were closely associated with short-term prognosis,” the researchers wrote. “Sequential measurement of inflammatory mediators may, therefore, be useful as predictors of treatment effectiveness and patient prognosis.” – by Will Offit

Disclosure: The researchers report no relevant financial disclosures.