Rapid and persistent decline in soluble CD163 with successful direct-acting antiviral therapy and associations with chronic hepatitis C histology

Abstract

Background and aim: Soluble CD 163 (sCD163) is released from activated liver macrophages in chronic viral hepatitis C (HCV) and serum levels reflect liver disease severity. The impact of direct-acting antiviral (DAA)-therapy on sCD163-levels and the ability of sCD163 to predict the presence of liver fibrosis remain unclear. In a combined observational and prospective study, we aimed to investigate changes in sCD163 with DAA-treatment, to investigate associations between sCD163 and histopathological activity and fibrosis and to validate the sCD163-based fibrosis score in HCV-patients.

Methods: We examined three groups of patients: an Australian (n = 28) treated with pegylated-interferon and a first-generation DAA, a Danish (n = 38) treated with sofosbuvir-based DAA-regimens and a Japanese (n = 562) assessed for activity and fibrosis (Metavir scoring system) in liver biopsies. Serum sCD163-levels were quantified by ELISA.

Results: Thirteen (46%) of the Australian patients achieved sustained virological response (SVR) and only these patients had significant decreases in sCD163-levels (2.7 (95%CI:1.9–3.6) vs. 4.1(2.9–5.7) mg L ^− 1, p = .008). In the Danish group, 37 (97%) patients achieved SVR at 12-weeks post-treatment with 32% reduction in sCD163-levels (5.0 (4.3–5.8) vs. 7.4 (6.3–8.7), p < .001). The decline was rapid and persisted 12 months after treatment cessation (p < .007). sCD163 levels increased in parallel with inflammatory activity and fibrosis (p < .001). The sCD163-based fibrosis score outperformed established fibrosis scores for significant fibrosis (areas under the receiver operating characteristics curves (AUROCs): 0.79 (0.75–0.83) vs. aspartate aminotransferase to platelet ratio index (APRI) 0.73 (0.69–0.77), Fibrosis-4 (FIB-4) 0.74 (0.70–0.78), p < .001).

Conclusion: sCD163-levels decline rapidly with successful DAA therapy and are associated with histological inflammatory activity and fibrosis, confirming a key role for macrophages in HCV inflammation and fibrosis and supporting sCD163 as a biomarker of treatment response.

Keywords:

• Inflammation
• fibrosis
• interferon treatment
• macrophages
• sofosbuvir

Disclosure statement

Holger Jon Møller has received research funding from the Danish Council for Strategic Research, is an independent contractor at IQ-Products, NL, hold a patent at Aarhus University and is a stock shareholder in Affinicon Aps. Jacob George has served as an advisory board member for Pharmaxis, BMS, MSD, Gilead, Janssen and Abbvie and has received research funding from MSD. Henning Grønbaek received funding from the NOVO Nordisk Foundation and ‘Savvaerksejer Jeppe Juhl og hustru Ovita Juhls mindelegat’. Henning Grønbaek has received research grants from Abbvie and Intercept and is on advisory board of Ipsen and Novartis. The work was independent from the funding. The authors have no other conflicts of interest to disclose.

Additional information

Funding

The study was supported by grants from The Danish Strategic Research Council (TRAIN 0603-00413B).