Thomas Damgaard Sandahl

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

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  • Tea Lund Laursen
  • Cecilie Brøckner Siggard, Denmark
  • Konstantin Kazankov
  • Thomas Damgaard Sandahl
  • Holger Jon Møller
  • Adrian Ong, c Storr Liver Centre , Westmead Institute for Medical Research, Westmead Hospital and University of Sydney , Sydney , Australia.
  • ,
  • Mark W Douglas, c Storr Liver Centre , Westmead Institute for Medical Research, Westmead Hospital and University of Sydney , Sydney , Australia.
  • ,
  • Jacob George, c Storr Liver Centre , Westmead Institute for Medical Research, Westmead Hospital and University of Sydney , Sydney , Australia.
  • ,
  • Britta Tarp
  • Lena Hagelskjaer Kristensen
  • Alex Lund Laursen
  • Akira Hiramatsu, g Department of Gastroenterology and Metabolism , Institute of Biomedical and Health Sciences, Hiroshima University , Hiroshima , Japan.
  • ,
  • Takashi Nakahara, g Department of Gastroenterology and Metabolism , Institute of Biomedical and Health Sciences, Hiroshima University , Hiroshima , Japan.
  • ,
  • Kazuaki Chayama, h Laboratory for Digestive Diseases , RIKEN Center for Integrative Medical Sciences , Hiroshima , Japan.
  • ,
  • Henning Grønbaek

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.

Original languageEnglish
JournalScandinavian Journal of Gastroenterology
Volume53
Issue8
Pages (from-to)986-993
Number of pages8
ISSN0036-5521
DOIs
Publication statusPublished - 10 Jul 2018

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