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

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Rapid and persistent decline in soluble CD163 with successful direct-acting antiviral therapy and associations with chronic hepatitis C histology. / Lund Laursen, Tea; Siggard, Cecilie Brøckner; Kazankov, Konstantin et al.

In: Scandinavian Journal of Gastroenterology, Vol. 53, No. 8, 10.07.2018, p. 986-993.

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@article{64f33152531544e58af661e584816ab4,
title = "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.",
author = "{Lund Laursen}, Tea and Siggard, {Cecilie Br{\o}ckner} and Konstantin Kazankov and {Damgaard Sandahl}, Thomas and M{\o}ller, {Holger Jon} and Adrian Ong and Douglas, {Mark W} and Jacob George and Britta Tarp and {Hagelskjaer Kristensen}, Lena and {Lund Laursen}, Alex and Akira Hiramatsu and Takashi Nakahara and Kazuaki Chayama and Henning Gr{\o}nbaek",
year = "2018",
month = jul,
day = "10",
doi = "10.1080/00365521.2018.1481996",
language = "English",
volume = "53",
pages = "986--993",
journal = "Scandinavian Journal of Gastroenterology",
issn = "0036-5521",
publisher = "Taylor & Francis ",
number = "8",

}

RIS

TY - JOUR

T1 - Rapid and persistent decline in soluble CD163 with successful direct-acting antiviral therapy and associations with chronic hepatitis C histology

AU - Lund Laursen, Tea

AU - Siggard, Cecilie Brøckner

AU - Kazankov, Konstantin

AU - Damgaard Sandahl, Thomas

AU - Møller, Holger Jon

AU - Ong, Adrian

AU - Douglas, Mark W

AU - George, Jacob

AU - Tarp, Britta

AU - Hagelskjaer Kristensen, Lena

AU - Lund Laursen, Alex

AU - Hiramatsu, Akira

AU - Nakahara, Takashi

AU - Chayama, Kazuaki

AU - Grønbaek, Henning

PY - 2018/7/10

Y1 - 2018/7/10

N2 - 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.

AB - 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.

U2 - 10.1080/00365521.2018.1481996

DO - 10.1080/00365521.2018.1481996

M3 - Journal article

C2 - 29987961

VL - 53

SP - 986

EP - 993

JO - Scandinavian Journal of Gastroenterology

JF - Scandinavian Journal of Gastroenterology

SN - 0036-5521

IS - 8

ER -