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Quantification of serum markers of hepatitis B (HBV) and Delta virus (HDV) infections in patients with chronic HDV infection
Authors:G. Ricco  D. C. Popa  D. Cavallone  S. Iacob  A. Salvati  D. Tabacelia  F. Oliveri  G. Mascolo  F. Bonino  Q. Yuan  N.‐S. Xia  L. Gheorghe  M. R. Brunetto
Affiliation:1. Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy;2. Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;3. Department of Biochemistry, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania;4. Bone Marrow Transplant Laboratory, Fundeni Clinical Institute, Bucharest, Romania;5. Department of Gastroenterology and Hepatology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania;6. Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania;7. Dia.Pro Diagnostic Bioprobes Srl, Sesto San Giovanni, Milan, Italy;8. University of Pittsburgh Medical Center (UPMC) Institute for Health, Chianciano Terme, Siena and Fondazione Italiana Fegato (FIF), AREA Science Park, Trieste, Italy;9. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
Abstract:The interplay between hepatitis B (HBV) and delta (HDV) viruses is complex and not always characterized during chronic HDV infection. We assessed the clinical usefulness of new quantitative assays for HBV and HDV serum markers in a retrospective cross‐sectional study. Sera obtained from 122 HDV genotype 1 and HBV genotype D coinfected, anti‐HIV‐negative patients (71 males; median age 49.8 [21.7‐66.9] years), recruited consecutively in two geographical areas (Italy 69 patients, Romania 53 patients) with different HBV and HDV epidemiology, were tested for HBsAg, HBV‐DNA, HBcrAg, total anti‐HBc, HDV‐RNA, IgM and total anti‐HDV using quantitative assays. Cirrhosis, which showed comparable prevalence in the two cohorts, was diagnosed in 97 of 122 (79.5%) patients. At multivariate analysis, cirrhosis was associated with lower total anti‐HBc/IgM anti‐HDV ratio (OR 0.990, 95% CI 0.981‐0.999, P = .038), whereas disease activity was associated with higher total anti‐HDV (OR 10.105, 95% CI 1.671‐61.107, P = .012) and HDV‐RNA levels (OR 2.366, 95% CI 1.456‐3.844, P = .001). HDV‐RNA serum levels showed a positive correlation with HBV‐DNA (ρ = 0.276, P = .005), HBsAg (ρ = 0.404, P < .001) and HBcrAg (ρ = 0.332, P < .001). The combined quantitative profiling of HBV and HDV serum markers identifies specific patterns associated with activity and stage of chronic hepatitis D (CHD). HDV pathogenicity depends on the underlying active HBV infection in spite of the inhibition of its replication. HDV‐RNA, IgM anti‐HDV, total anti‐HDV, total anti‐HBc, HBsAg and HBcrAg serum levels qualify for prospective studies to predict progressive CHD and identify candidates to antiviral therapy.
Keywords:chronic hepatitis D  hepatitis B virus  hepatitis delta virus  quantitative assay  serum markers
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