• Lund Laursen Tea T a Department of Hepatology & Gastroenterology , Aarhus University Hospital , Aarhus , Denmark., Cecilie Brøckner Siggard, Konstantin Kazankov, Damgaard Sandahl Thomas T a Department of Hepatology & Gastroenterology , Aarhus University Hospital , Aarhus , Denmark., Holger Jon Møller, Adrian Ong, Mark W Douglas, Jacob George, Britta Tarp, Lena Hagelskjaer Kristensen, Alex Lund Laursen, Akira Hiramatsu, Takashi Nakahara, Kazuaki Chayama, and Henning Grønbaek.
• a Department of Hepatology & Gastroenterology , Aarhus University Hospital , Aarhus , Denmark.
• Scand. J. Gastroenterol. 2018 Aug 1; 53 (8): 986-993.

Background And AimSoluble 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.MethodsWe 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.ResultsThirteen (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).ConclusionsCD163-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.

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