PLoS ONE (Jan 2014)

Anti-HDV IgM as a marker of disease activity in hepatitis delta.

  • Anika Wranke,
  • Benjamin Heidrich,
  • Stefanie Ernst,
  • Beatriz Calle Serrano,
  • Florin Alexandru Caruntu,
  • Manuela Gabriela Curescu,
  • Kendal Yalcin,
  • Selim Gürel,
  • Stefan Zeuzem,
  • Andreas Erhardt,
  • Stefan Lüth,
  • George V Papatheodoridis,
  • Birgit Bremer,
  • Judith Stift,
  • Jan Grabowski,
  • Janina Kirschner,
  • Kerstin Port,
  • Markus Cornberg,
  • Christine S Falk,
  • Hans-Peter Dienes,
  • Svenja Hardtke,
  • Michael P Manns,
  • Cihan Yurdaydin,
  • Heiner Wedemeyer,
  • HIDIT-2 Study Group

DOI
https://doi.org/10.1371/journal.pone.0101002
Journal volume & issue
Vol. 9, no. 7
p. e101002

Abstract

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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.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).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).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.