Patient characteristics at baseline
A total of 581 patients were included in this study and 92 (15.8%) patients had advanced fibrosis at baseline. Patients with advanced fibrosis and those without advanced fibrosis were similar in gender, BMI, hypertriglyceridemia and proportion of HBsAg positive. However, the mean age of patients with advanced fibrosis was higher than those without advanced fibrosis (58.8 versus 53.6 years, P < 0.001). Patients with advanced fibrosis had significantly higher prevalence of high HCV RNA level (87.0% versus 72.4%, P = 0.003). Patients with advanced fibrosis were more likely to have hyperglycaemia (29.3% versus 14.1%, P < 0.001) and less likely to have hypercholesterolemia (1.1% versus 7.4%, P = 0.024). Features of the study populations and differences in the variables potentially associated with advanced fibrosis are shown in Table 1.
Univariate and multivariate analysis of variables associated with advanced fibrosis
The results of univariate and multivariate analysis are provided in Table 2. According to univariate analysis, older age (OR=3.17, 95% CI: 1.94-5.19), high HCV RNA viral load (OR=2.54, 95% CI: 1.34-4.81), and hyperglycaemia (OR=2.53, 95% CI: 1.51-4.24) were associated with an increased probability of advanced fibrosis. After adjusting for potential confounders, older age (OR=2.99, 95% CI: 1.80-4.95), high HCV RNA viral load (OR=2.25, 95% CI: 1.17-4.33), and hyperglycaemia (OR=2.33, 95% CI: 1.36-4.00) were the only three variables independently associated with advanced liver fibrosis on multivariate analysis. Patients with hyperglycaemia compared to those without hyperglycaemia had a 2.33-fold increased rate of advanced fibrosis.
Baseline factors associated with longitudinal progression of fibrosis
We analyzed the longitudinal progression of fibrosis in 581 CHC patients who underwent 2 assessments of FIB-4. Compared with baseline, the median value of FIB-4 score was significantly higher at two-year follow up visit (2.91 versus 1.84, P < 0.001). At two-year follow-up, 55.2% (321 of 581) of patients had no advanced fibrosis (FIB-4 ≤3.25) and 3.4% (11 of 581) of patients had improvement of fibrosis (defined as FIB-4 reversion to ≤ 3.25). However, 28.9% (168 of 581) of patients experienced progression of fibrosis (defined as FIB-4 elevation to > 3.25) and 13.9% (81 of 581) of patients presented persistent advanced fibrosis (defined as FIB-4 > 3.25 at both two visits). Baseline factors associated with longitudinal FIB-4 patterns were shown in Table 3. In multivariable analysis, older age (OR=2.77, 95% CI: 1.85-4.14), heavy alcohol consumption (OR=2.03, 95% CI: 1.22-3.37), and high HCV RNA viral load (OR=3.01, 95% CI: 1.82-4.97) were positively associated with progression of advanced fibrosis. Older age (OR=4.57, 95% CI: 2.58-8.08), hyperglycaemia (OR=3.53, 95% CI: 1.69-7.38), and high HCV RNA viral load (OR=2.44, 95% CI: 1.28-4.65) were independently associated with increased risk of persistent advanced fibrosis. As shown in Table 4.
The impact of longitudinal changes of serum glucose levels on advanced fibrosis
During a two-year follow-up, 78% (453 of 581) patients showed persistent normal fasting blood glucose, defined as FBG < 100 mg/dL both at baseline and two-years follow-up visit. 22.0% (128 of 581) patients had intermittent/persistent fasting blood glucose elevation, defined as FBG ≥ 100 mg/dL at one or two visits. At two-year follow up visit, the median value of FIB-4 score in patients with intermittent or persistent FBG elevation was higher than that in patients with persistent normal FBG (2.85 versus 3.23, P = 0.031), as shown in Fig 1. A significant higher prevalence of intermittent/persistent fasting blood glucose elevation was observed in patients with persistent FIB-4 > 3.25 than in patients with persistent normal FIB-4 (Fig 2).