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

  • 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.

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Author:Anika Wranke, Benjamin Heidrich, Stefanie Ernst, Beatriz Calle Serrano, Florin Alexandru Caruntu, Manuela Gabriela Curescu, Kendal Yalcin, Selim Gürel, Stefan ZeuzemORCiDGND, Andreas Erhardt, Stefan Lüth, George V. Papatheodoridis, Birgit Bremer, Judith Stift, Jan Grabowski, Janina Kirschner, Kerstin Port, Markus Cornberg, Christine S. Falk, Hans-Peter DienesGND, Svenja Hardtke, Michael P. Manns, Cihan Yurdaydin, Heiner WedemeyerORCiDGND
Pubmed Id:
Parent Title (English):PLoS One
Place of publication:Lawrence, Kan.
Document Type:Article
Date of Publication (online):2014/07/29
Date of first Publication:2014/07/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/10/18
Page Number:13
Copyright: © 2014 Wranke et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0