SC-5 HDV persistence is sustained by HBsAg mainly derived from integrated HBV-DNA and is independent from the extent of HBV reservoir
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Le résumé fourni par la source
Background HDV exploits HBV surface glycoproteins (HBsAg) for viral morphogenesis and infectivity. Here, we investigate HBV and HDV activities and their interplay in liver biopsies from patients (pts) with chronic HDV infection (CHD) and HBV monoinfection (CHB). Methods 68 HBeAg-negative pts (75% NUC treated) are included: 32 with CHD and 36 with CHB. Intrahepatic levels of cccDNA, pgRNA and HDV-RNA were assessed by droplet digital PCR (ddPCR). ddPCR assays were set-up to quantify total HBs transcripts and to distinguish those deriving from cccDNA and from integrated HBV-DNA (Grudda, 2022). Results Pts with CHD and CHB are comparable in terms of age and NUC-treatment duration (median [IQR] age and NUC duration: 49 [39–59] and 42 [34–60] years; 6 [4–12] and 6 [4–7] years). As expected, CHD has lower serum HBV-DNA than CHB (median [IQR]: 20 [12–50] vs 3,981 [251–79,432] IU/ml, P<0.0001). CHD is characterized by higher ALT levels and advanced fibrosis status (median [IQR] ALT: 68 [45–89] vs 28 [21–49] U/l, P=0.001; Fibrosis score>F5 in 53.3% vs 19.4%, P=0.005). Median (IQR) serum HDV-RNA is 6.0 (3.8–6.7) logIU/ml, positively correlated with intrahepatic HDV-RNA (Rho=0.62, P=0.006; 784 [1–4,266] copies/1000cells). CHD presents a more restricted HBV reservoir in terms of cccDNA and pgRNA (median [IQR]: 1 (0.02–16) vs 10 (2–18) copies/1000cells, P=0.02 and 10 [1–173] vs 72 [38–380] copies/1000cells, P=0.08, respectively). Nevertheless, both CHD and CHB are characterized by a substantial production of HBs transcripts (median [IQR]: 6,267 [345–31,387] and 8,081 [314–15,189]), with >99% of them deriving from integrated HBV-DNA. By stratifying CHD pts according to cccDNA size, lower levels of HBV intrahepatic markers are observed in those with a restricted HBV reservoir (median [IQR] pgRNA and cccDNA-derived transcripts: 1.4 [0.4–78] vs 108 [5–411], P=0.01 and 0.3 [0.2–1.5] vs 48 [9.6–186] copies/1000cells, P=0.002 in cccDNA<1 vs cccDNA>1 copy/1000cells). Conversely, no differences are observed for intrahepatic HDV-RNA levels (median [IQR]: 782 [1–5,559] vs 844 [1–6,371] copies/1000cells, P=0.6). Even more, among the 32 CHD pts, 7 showed undetectable cccDNA, cccDNA-derived HBs transcripts and serum HBV-DNA. Nevertheless, these patients are characterized by a considerable amount of intrahepatic and serum HDV-RNA (median [IQR]: 1,659 [660–12,261] copies/1000cells and 6.0 [5.9–7.3] log IU/ml, respectively), as well as by the presence of HBs transcripts derived from integrated HBV-DNA (median [IQR]: 3 [2–690] copies/1000 cells), supporting that HDV persistence can be sustained by HBsAg derived from integrated HBV-DNA. Conclusions Pathways sustaining HDV persistence act independently from the extent of intrahepatic HBV reservoir and are fueled by an intense production of HBs transcripts, mainly derived from integrated HBV-DNA. In this light, pharmacological strategies should take into account HBsAg production from integrated HBV-DNA for achieving HDV cure.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- SC-5 HDV persistence is sustained by HBsAg mainly derived from integrated HBV-DNA and is independent from the extent of HBV reservoir
- Date Crossref
- 01/06/2024
- Éditeur
- BMJ Publishing Group Ltd
- Type
- proceedings-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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University of Rome Tor Vergata Department of Experimental Medicine pays non établi dans la noticeUniversité ou école supérieure
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University of Padua Department of Molecular Medicine pays non établi dans la noticeUniversité ou école supérieure
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CTO Andrea Alesini pays non établi dans la noticeÉtablissement de santé
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Policlinico Tor Vergata Hepatology Unit pays non établi dans la noticeÉtablissement de santé
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Department of Experimental Medicine — University of Rome Tor Vergata, Department of Molecular Medicine — University of Padua et CTO Andrea Alesini, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.