Anti-HDV IgM as a marker of disease activity in hepatitis delta
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Anti-HDV IgM as a marker of disease activity in hepatitis delta. / HIDIT-II Study Group.
In: PLOS ONE, Vol. 9, No. 7, 2014, p. e101002.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Anti-HDV IgM as a marker of disease activity in hepatitis delta
AU - Wranke, Anika
AU - Heidrich, Benjamin
AU - Ernst, Stefanie
AU - Calle Serrano, Beatriz
AU - Caruntu, Florin Alexandru
AU - Curescu, Manuela Gabriela
AU - Yalcin, Kendal
AU - Gürel, Selim
AU - Zeuzem, Stefan
AU - Erhardt, Andreas
AU - Lüth, Stefan
AU - Papatheodoridis, George V
AU - Bremer, Birgit
AU - Stift, Judith
AU - Grabowski, Jan
AU - Kirschner, Janina
AU - Port, Kerstin
AU - Cornberg, Markus
AU - Falk, Christine S
AU - Dienes, Hans-Peter
AU - Hardtke, Svenja
AU - Manns, Michael P
AU - Yurdaydin, Cihan
AU - Wedemeyer, Heiner
AU - HIDIT-II Study Group
PY - 2014
Y1 - 2014
N2 - BACKGROUND: Hepatitis delta frequently leads to liver cirrhosis and hepatic decompensation. As treatment options are limited, there is a need for biomarkers to determine disease activity and to predict the risk of disease progression. We hypothesized that anti-HDV IgM could represent such a marker.METHODS: Samples of 120 HDV-infected patients recruited in an international multicenter treatment trial (HIDIT-2) were studied. Anti-HDV IgM testing was performed using ETI-DELTA-IGMK-2-assay (DiaSorin). In addition, fifty cytokines, chemokines and angiogenetic factors were measured using multiplex technology (Bio-Plex System). A second independent cohort of 78 patients was studied for the development of liver-related clinical endpoints (decompensation, HCC, liver transplantation or death; median follow up of 3.0 years, range 0.6-12).RESULTS: Anti-HDV IgM serum levels were negative in 18 (15%), low (OD<0.5) in 76 (63%), and high in 26 (22%) patients of the HIDIT-2 cohort. Anti-HDV IgM were significantly associated with histological inflammatory (p<0.01) and biochemical disease activity (ALT, AST p<0.01). HDV replication was independent from anti-HDV IgM, however, low HBV-DNA levels were observed in groups with higher anti-HDV IgM levels (p<0.01). While high IP-10 (CXCL10) levels were seen in greater groups of anti-HDV IgM levels, various other antiviral cytokines were negatively associated with anti-HDV IgM. Associations between anti-HDV IgM and ALT, AST, HBV-DNA were confirmed in the independent cohort. Clinical endpoints occurred in 26 anti-HDV IgM positive patients (39%) but in only one anti-HDV IgM negative individual (9%; p = 0.05).CONCLUSIONS: Serum anti-HDV IgM is a robust, easy-to-apply and relatively cheap marker to determine disease activity in hepatitis delta which has prognostic implications. High anti-HDV IgM levels may indicate an activated interferon system but exhausted antiviral immunity.
AB - BACKGROUND: Hepatitis delta frequently leads to liver cirrhosis and hepatic decompensation. As treatment options are limited, there is a need for biomarkers to determine disease activity and to predict the risk of disease progression. We hypothesized that anti-HDV IgM could represent such a marker.METHODS: Samples of 120 HDV-infected patients recruited in an international multicenter treatment trial (HIDIT-2) were studied. Anti-HDV IgM testing was performed using ETI-DELTA-IGMK-2-assay (DiaSorin). In addition, fifty cytokines, chemokines and angiogenetic factors were measured using multiplex technology (Bio-Plex System). A second independent cohort of 78 patients was studied for the development of liver-related clinical endpoints (decompensation, HCC, liver transplantation or death; median follow up of 3.0 years, range 0.6-12).RESULTS: Anti-HDV IgM serum levels were negative in 18 (15%), low (OD<0.5) in 76 (63%), and high in 26 (22%) patients of the HIDIT-2 cohort. Anti-HDV IgM were significantly associated with histological inflammatory (p<0.01) and biochemical disease activity (ALT, AST p<0.01). HDV replication was independent from anti-HDV IgM, however, low HBV-DNA levels were observed in groups with higher anti-HDV IgM levels (p<0.01). While high IP-10 (CXCL10) levels were seen in greater groups of anti-HDV IgM levels, various other antiviral cytokines were negatively associated with anti-HDV IgM. Associations between anti-HDV IgM and ALT, AST, HBV-DNA were confirmed in the independent cohort. Clinical endpoints occurred in 26 anti-HDV IgM positive patients (39%) but in only one anti-HDV IgM negative individual (9%; p = 0.05).CONCLUSIONS: Serum anti-HDV IgM is a robust, easy-to-apply and relatively cheap marker to determine disease activity in hepatitis delta which has prognostic implications. High anti-HDV IgM levels may indicate an activated interferon system but exhausted antiviral immunity.
KW - Adult
KW - Biomarkers/blood
KW - Coinfection
KW - Cross-Sectional Studies
KW - Cytokines/metabolism
KW - Female
KW - Hepatitis Antibodies/blood
KW - Hepatitis B, Chronic
KW - Hepatitis D/diagnosis
KW - Hepatitis D, Chronic/diagnosis
KW - Hepatitis Delta Virus/immunology
KW - Humans
KW - Immunoglobulin M/blood
KW - Liver/immunology
KW - Liver Function Tests
KW - Male
KW - Middle Aged
KW - Patient Outcome Assessment
KW - Severity of Illness Index
U2 - 10.1371/journal.pone.0101002
DO - 10.1371/journal.pone.0101002
M3 - SCORING: Journal article
C2 - 25072849
VL - 9
SP - e101002
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 7
ER -
