Modifications of liver stiffness and CXCL4, TGF-β1 and HGF are similar in HCV- and HIV/HCV-infected patients after DAAs

Abstract

The objective of this work was to identify predictive factors of fibrosis regression after direct antiviral agents (DAAs) in HCV-monoinfected and HIV/HCV-coinfected patients. This was a prospective study of HCV-monoinfected (n = 20), HIV/HCV-co-infected (n = 66) patients and healthy controls (n = 15). Patients had started DAAs and achieved sustained virological response. Liver stiffness (LS) and serum concentrations of profibrotic transforming growth factor (TGF)-β1 and CXC chemokine ligand 4 (CXCL4) and antifibrotic HGF hepatocyte growth factor (HGF) were analyzed at baseline (M0) and 12 months after starting DAAs (M12). A M12 LS achievement of ≤ 9.5 kPa was considered the cutoff point to discharge from a liver clinic. The LS decrease from M0 to M12 was 34%. No significant differences were observed in LS decline between HCV- and HIV/HCV-infected individuals. Changes of serum CXCL4, TGF-β1 and HGF levels did not correlate with LS improvement. 16 out from 56 patients (28%) with a baseline LS > 9.5 achieved a M12 LS ≤ 9.5. HCV-monoinfected and HIV/HCV coinfected patients experienced a significant reduction of LS after sustained virological response. This improvement did not correlate with changes in serum profibrotic or antifibrotic markers. A 29% of those with a baseline LS > 9.5 achieved a LS under this cutoff point.

Figure 1

Bivariate correlation between changes in liver stiffness and serum concentrations of chemokine (C-X-C motif) ligand 4 (CXCL4) (A); transforming growth factor β1 (TGF-β1) (B), and hepatocyte growth factor (HGF) (C) concentrations in HCV-infected patients (n = 86), from inclusion (M0) to 12 months after that (M12). Patients started with direct HCV antiviral agents at inclusion and achieved sustained viral HCV response. Data are shown as percentage of change [100 × (M12 − M0)/M0].

Figure 2

Changes in liver stiffness (A), serum chemokine (C-X-C motif) ligand 4 (CXCL4) (B), transforming growth factor β1 (TGF-β1) (C), and hepatocyte growth factor (HGF) (D) concentrations in HCV-infected patients with (n = 32) or without (n = 54) liver cirrhosis, from inclusion to 12 months after that. Patients started with direct HCV antiviral agents at inclusion and achieved sustained viral HCV response. Data are shown as median, interquartile range and range.

Figure 3

Changes in liver stiffness (A), serum chemokine (C-X-C motif) ligand 4 (CXCL4) (B), transforming growth factor β1 (TGF-β1) (C), and hepatocyte growth factor (HGF) (D) concentrations in HCV-infected patients without (HCV + HIV−) (n = 20) or with (HCV + HIV +) (n = 66) HIV coinfection, from inclusion to 12 months after that. Patients started with direct HCV antiviral agents at inclusion and achieved sustained viral HCV response. Data are shown as median, interquartile range and range.