Association between the systemic immune-inflammation index and the outcome of liver fibrosis in patients with chronic hepatitis C

Abstract

Background: Risk factors that influence the outcome of patients with chronic hepatitis C (CHC) are not fully understood. The systemic immune-inflammatory index (SII) is an independent prognostic factor for multiple diseases. However, the impact of the SII on the outcome of liver fibrosis is unclear.

Methods: This prospective real-world study enrolled patients with CHC treated with sofosbuvir/velpatasvir. Logistic regression models were used to investigate the relationship between the SII and the outcome of liver fibrosis in treatment-naive patients. Liver fibrosis was assessed using aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4).

Results: Of the 288 participants, the SII was 238.2 (153.0-358.2). The non-improved outcomes of liver fibrosis assessed with APRI (non-improved APRI) and FIB-4 (non-improved FIB-4) were 83.0 and 87.5%, respectively. Adjusted models showed that the SII was positively associated with non-improved APRI (adjusted OR (95% CI): 1.013 (1.009-1.017), p < 0.001) and FIB-4 (adjusted OR (95% CI): 1.004 (1.001-1.007), p = 0.012). Similarly, a higher SII was associated with a higher risk of non-improved APRI (adjusted OR (95% CI): 13.53 (5.60-32.68), p < 0.001) and FIB-4 (adjusted OR (95% CI): 5.69 (2.17-14.90), p < 0.001). The association with non-improved APRI was much more remarkable in patients with alanine aminotransferase <2 ULN, and the association with non-improved FIB-4 was remarkable in patients aged <50 years. Multiple imputation analyses confirmed the robustness of these results.

Conclusion: Our findings suggested that the SII was positively associated with non-improved outcomes of liver fibrosis in patients with CHC. These results need to be validated in large-scale prospective cohorts.

Keywords: chronic hepatitis C; liver fibrosis; outcome; risk factor; systemic immune-inflammation index.

Figure 1

Patients’ selection. HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; COVID-19, coronavirus disease 2019; SII, systemic immune-inflammation index; FIB-4, fibrosis-4; APRI, aspartate aminotransferase-to-platelet ratio index.

Figure 2

Univariate and multivariate logistic regression analyses to identify the association between SII and the outcome of liver fibrosis. (A) Analysis with continuous SII; (B) Analysis with stratified SII. SII, systemic immune-inflammation index; FIB-4, fibrosis-4; APRI, aspartate aminotransferase-to-platelet ratio index; OR, odds ratio; CI, confidence interval. Model 1: a crude model adjusted for none. Model 2: a partially adjusted model including sex (female vs. male), age (years), liver cirrhosis (yes vs. no), and ribavirin administration (yes vs. no). Model 3: a fully adjusted model including covariates in model 2 and HCV RNA(lg10 IU/L), HCV genotype (vs. 1), baseline total bilirubin (μmol/L), baseline alanine aminotransferase (×ULN), albumin (g/L), and baseline serum creatinine (×ULN).

Figure 3

Stratified logistic regression analysis to identify variables that modify the correlation between continuous SII and the outcome of liver fibrosis. SII, systemic immune-inflammation index; APRI, aspartate aminotransferase-to-platelet ratio index; FIB-4, fibrosis-4; ALT, alanine aminotransferase; ULN, upper limit of normal value; OR, odds ratio; CI, confidence interval. Adjusted OR^&: a fully adjusted model (Model 3) adjusted for sex (female vs. male), age (years), liver cirrhosis (yes vs. no), ribavirin administration (yes vs. no), HCV RNA(lg10 IU/L), HCV genotype (vs. 1), baseline total bilirubin (μmol/L), baseline alanine aminotransferase (×ULN), baseline albumin (g/L), and baseline serum creatinine (×ULN).

Figure 4

Stratified logistic regression analysis to identify variables that modify the correlation between stratified SII and the outcome of liver fibrosis. SII, systemic immune-inflammation index; APRI, aspartate aminotransferase-to-platelet ratio index; FIB-4, fibrosis-4; ALT, alanine aminotransferase; ULN, upper limit of normal value; OR, odds ratio; CI, confidence interval. Adjusted OR^&: a fully adjusted model (Model 3) adjusted for sex (female vs. male), age (years), liver cirrhosis (yes vs. no), ribavirin administration (yes vs. no), HCV RNA(lg10 IU/L), HCV genotype (vs. 1), baseline total bilirubin (μmol/L), baseline alanine aminotransferase (×ULN), baseline albumin (g/L), and baseline serum creatinine (×ULN).

Figure 5

Multiple imputation analysis for the detection of sensitivity. (A) Analysis with continuous SII; (B) Analysis with stratified SII. Model 1: a crude model adjusted for none. Model 2: a partially adjusted model including sex (female vs. male), age (years), liver cirrhosis (yes vs. no), and ribavirin administration (yes vs. no). Model 3: a fully adjusted model including covariates in model 2 and HCV RNA(lg10 IU/L), HCV genotype (vs. 1), baseline total bilirubin (μmol/L), baseline alanine aminotransferase (×ULN), baseline albumin (g/L), and baseline serum creatinine (×ULN).