Wranke, AnikaHeidrich, BenjaminErnst, StefanieSerrano, Beatriz CalleCaruntu, Florin AlexandruCurescu, Manuela GabrielaYalcin, KendalGürel, SelimZeuzem, StefanErhardt, AndreasLueth, StefanPapatheodoridis, George V.Bremer, BirgitStift, JudithGrabowski, JanKirschner, JaninaPort, KerstinCornberg, MarkusFalk, Christine S.Dienes, Hans-PeterHardtke, SvenjaManns, Michael P.Yurdaydin, CihanWedemeyer, HeinerHIDIT-2 Study Grp2024-08-152024-08-152014-07-291932-6203https://doi.org/10.1371/journal.pone.0101002https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101002https://hdl.handle.net/11452/44057Background: 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.eninfo:eu-repo/semantics/openAccessB-virusLiver-transplantationInterferonInfectionChallengesAntibodiesProfilesTherapyCellsScience & technology - other topicsArticle0003413076000059710.1371/journal.pone.0101002