Association between systemic immune inflammation index and short term prognosis of acute on chronic liver failure

Abstract

The systemic immune-inflammatory index (SII) has been identified as an independent prognostic factor for multiple diseases. However, the impact of SII on outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective study enrolled patients with ACLF treated with artificial liver support system. Restricted cubic spline (RCS) (knots at the 10th, 50th, and 90th percentiles) and Cox proportional hazards models were applied to investigate the relationship between SII and 90-day transplant-free survival and overall survival in patients with ACLF. A total of 258 patients with ACLF were included. The 90-day transplant-free survival rate and overall survival rate were 58.5% and 66.3%. The SII was 465.5 (277.3-804.4). Adjusted RCS models showed linear exposure-response relationship between SII and 90-day transplant-free survival (P for overall < 0.001, P for nonlinear = 0.154) and 90-day overall survival (P for overall < 0.001, P for nonlinear = 0.103), and adjusted Cox models confirmed the positive relationship. Compared with patients with SII < 480, patients with ≥ 480 had more serious condition, lower 90-day transplant-free survival rate (46.8% vs. 69.7%, adjusted HR (95% CI) for transplant or death: 2.13 (1.40-3.23), P < 0.001), and lower 90-day overall survival rate (56.3% vs. 75.8%; adjusted HR (95% CI) for death: 2.26 (1.42-3.61), P = 0.001). Stratified Cox models suggested no potential modifiers in the relationship between SII and 90-day transplant-free survival. Our findings suggested SII was positively associated with poor short-term prognosis of ACLF.

Keywords: Acute-on-chronic liver failure; Artificial liver support system; Outcome; Risk factor; Systemic immune-inflammation index.

Fig. 1

Patients selection and follow-up. ALSS, artificial liver support system; DPMAS, double plasma molecular adsorption system; PE, plasma exchange; RCA, regional citrate anticoagulation; HBV, hepatitis B virus; PT-INR, international normalized ratio (INR) of prothrombin time (PT); ACLF, acute-on-chronic liver failure; SII, systemic immune-inflammation index.

Fig. 2

Relationship between SII and short-term prognosis of ACLF. SII, systemic immune-inflammation index; ACLF, acute-on-chronic liver failure; HR, hazard ratio; CI, confidence interval; TFS, transplant-free survival; OS, overall survival. Model 1 was a crude Cox model adjusted for none. Model 2 was a partially adjusted Cox model adjusted for age (years), gender (female vs. male), liver cirrhosis (yes vs. no), HBV DNA (log10 IU/mL), other co-existing liver diseases (yes vs. no), comorbidities (yes vs. no). Model 3 was a fully adjusted Cox model including model 2 covariates plus disease severity (COSSH ACLF score). Model 4 was a fully adjusted Cox model including model 3 covariates plus, sessions of artificial liver support system therapy (continuous values), and liver transplantation just for overall survival analysis (yes vs. no). The restricted cubic spline model (knots at the 10th, 50th, and 90th percentiles) was a fully adjusted model including the same covariates in Model 3.

Fig. 3

Survival curves of patients with ACLF and different stratified SII. SII, systemic immune-inflammation index; ACLF, acute-on-chronic liver failure; HR, hazard ratio; CI, confidence interval; TFS, transplant-free survival; OS, overall survival. Model 1 was a crude Cox model adjusted for none. Model 2 was a partially adjusted Cox model adjusted for age (years), gender (female vs. male), liver cirrhosis (yes vs. no), HBV DNA (log10 IU/mL), other co-existing liver diseases (yes vs. no), comorbidities (yes vs. no). Model 3 was a fully adjusted Cox model including model 2 covariates plus disease severity (COSSH ACLF score), sessions of artificial liver support system therapy (continuous values), and liver transplantation just for overall survival analysis (yes vs. no).

Fig. 4

Stratified Cox regression analysis to identify variables that modify the relationship between SII and 90-day transplant-free survival of ACLF. SII, systemic immune-inflammation index; ACLF, acute-on-chronic liver failure; ALSS, artificial liver support system; HR, hazard ratio; CI, confidence interval. Adjusted HR^&: multivariable Cox regression analysis (Model 3) includes SII (continuous SII), age (years), gender (female vs. male), liver cirrhosis (yes vs. no), HBV DNA (log10 IU/mL), other co-existing liver diseases (yes vs. no), comorbidities (yes vs. no), disease severity (COSSH ACLF score) and sessions of artificial liver support system therapy (continuous values).

Fig. 5

Stratified Cox regression analysis to identify variables that modify the relationship between stratified SII and 90-day transplant-free survival of ACLF. SII, systemic immune-inflammation index; ACLF, acute-on-chronic liver failure; ALSS, artificial liver support system; HR, hazard ratio; CI, confidence interval. Adjusted HR^&: multivariable Cox regression analysis (Model 3) includes SII (stratified SII), age (years), gender (female vs. male), liver cirrhosis (yes vs. no), HBV DNA (log10 IU/mL), other co-existing liver diseases (yes vs. no), comorbidities (yes vs. no), disease severity (COSSH ACLF score) and sessions of artificial liver support system therapy (continuous values).