Blood markers for type-1,-2, and -3 inflammation are associated with severity of acutely decompensated cirrhosis

Background and aims

In patients with acutely decompensated cirrhosis (ADC) who present with clinically apparent precipitants (i.e., infections, acute liver injury), alterations in blood markers of inflammation associate with progression toward severe phenotypes (e.g., acute-on-chronic liver failure, ACLF). It is unclear whether alterations in blood inflammatory markers may associate with progression of ADC independently of precipitants.

Methods

We prospectively enrolled 394 patients admitted for ADC who were classified into four phenotypes of increasing severity: no organ dysfunction (n=168), organ dysfunction alone (n=72), organ failure without ACLF (n=91), and ACLF (n=63). Clinical blood cell counts and serum levels of inflammatory markers (including soluble markers related to type-1, type-2, and type-3 inflammation) were obtained at enrollment. Ordinal regression with adjacent categories logit model adjusted for confounders (including precipitants) was used to analyze associations between changes in each blood inflammatory marker and the worsening of ADC.

Results

Inflammatory markers that were associated with higher risk of progressing to the next more severe stage were as follows: increasing neutrophil counts (adjusted common odds ratio [cOR] 1.17, 95%CI 1.06-1.28); increasing levels of the type-2 cytokine interleukin (IL)-25 (cOR 1.21, 95%CI 1.06-1.39), type-3 cytokines IL-6 (cOR 1.15, 95%CI 1.02-1.28) and IL-22 (cOR 1.16, 95%CI 1.03-1.30), or anti-inflammatory soluble CD163 (cOR 1.94, 95%CI 1.58-2.38); decreasing lymphocyte counts (cOR 0.77, 95%CI 0.68-0.87), or decreasing levels of the type-1 cytokine IFN-γ (cOR 0.85, 95%CI 0.75-0.95).

Conclusions

Among patients with ADC, alterations in blood levels of cytokines related to type-1, type-2 and type-3 inflammation, together with neutrophilia, lymphopenia and elevated anti-inflammatory signals were individually associated with an increased risk of progressing toward ACLF, independently of the presence of clinically apparent precipitants.