Large spatial variation of intrahepatic HDV RNA levels without association with HBV core or S RNA levels in HDV cirrhosis patients

The aim of this study was to investigate correlations between levels of intrahepatic HDV RNA, HBV RNA and corresponding serum markers in patients who underwent transplantation because of HDV-induced liver disease. 10 pieces of tissue from each of five liver explants from patients that underwent tran...

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Published in:	Journal of clinical virology Vol. 181; p. 105871
Main Authors:	Rydell, Gustaf E., Strömberg, Lucia Gonzales, Ringlander, Johan, Andersson, Maria E., Skoglund, Catarina, Stenbäck, Joakim Bedner, Nilsson, Staffan, Castedal, Maria, Lindh, Magnus
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01.12.2025
Subjects:	Adult Aged ddPCR Female HBV integration HCC HDV Hepatitis B Core Antigens - genetics Hepatitis B Surface Antigens - blood Hepatitis B Surface Antigens - genetics Hepatitis B virus - genetics Hepatitis D - complications Hepatitis D - virology Hepatitis Delta Virus - genetics Hepatitis Delta Virus - isolation & purification Humans Infectious Medicine Infektionsmedicin Liver - virology Liver Cirrhosis - virology Male Middle Aged RNA, Viral - analysis RNA, Viral - blood RNA, Viral - genetics Viral Load ddPCR cccDNA nt HCC HBsAg HBV integration HDV HBV
ISSN:	1386-6532, 1873-5967, 1873-5967
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Abstract	The aim of this study was to investigate correlations between levels of intrahepatic HDV RNA, HBV RNA and corresponding serum markers in patients who underwent transplantation because of HDV-induced liver disease. 10 pieces of tissue from each of five liver explants from patients that underwent transplantation because of HDV-induced liver disease were analyzed by digital droplet PCR. A large variation of the tissue levels of viral RNA was found both between and within patients. Overall, tissue levels of HBV core and S RNA were positively associated. However, no consistent association was observed between tissue levels of HDV RNA and either core or S RNA, except in one patient. Furthermore, intrahepatic HDV RNA levels did not correlate with serum HDV RNA. Instead, serum HDV RNA showed a positive correlation with serum HBsAg, a trend towards correlation with tissue HBV S RNA and a significant correlation with core RNA levels. The results suggest that intrahepatic HBsAg might be a limiting factor for HDV particle secretion, but do not support the hypothesis that HDV suppresses HBV replication. •HBV RNA and HDV RNA levels in liver tissue varied between and within patients.•Tissue levels of HDV RNA were not associated with HBV core or S RNA.•This observation does not support repression of HBV replication by HDV.•Serum HDV RNA correlated with serum HBsAg and tended to correlate with tissue S RNA.•This observation suggests that the HBsAg supply might limit HDV virion production.
AbstractList	Background: The aim of this study was to investigate correlations between levels of intrahepatic HDV RNA, HBV RNA and corresponding serum markers in patients who underwent transplantation because of HDV-induced liver disease. Methods: 10 pieces of tissue from each of five liver explants from patients that underwent transplantation because of HDV-induced liver disease were analyzed by digital droplet PCR. Results: A large variation of the tissue levels of viral RNA was found both between and within patients. Overall, tissue levels of HBV core and S RNA were positively associated. However, no consistent association was observed between tissue levels of HDV RNA and either core or S RNA, except in one patient. Furthermore, intrahepatic HDV RNA levels did not correlate with serum HDV RNA. Instead, serum HDV RNA showed a positive correlation with serum HBsAg, a trend towards correlation with tissue HBV S RNA and a significant correlation with core RNA levels. Conclusions: The results suggest that intrahepatic HBsAg might be a limiting factor for HDV particle secretion, but do not support the hypothesis that HDV suppresses HBV replication. The aim of this study was to investigate correlations between levels of intrahepatic HDV RNA, HBV RNA and corresponding serum markers in patients who underwent transplantation because of HDV-induced liver disease. 10 pieces of tissue from each of five liver explants from patients that underwent transplantation because of HDV-induced liver disease were analyzed by digital droplet PCR. A large variation of the tissue levels of viral RNA was found both between and within patients. Overall, tissue levels of HBV core and S RNA were positively associated. However, no consistent association was observed between tissue levels of HDV RNA and either core or S RNA, except in one patient. Furthermore, intrahepatic HDV RNA levels did not correlate with serum HDV RNA. Instead, serum HDV RNA showed a positive correlation with serum HBsAg, a trend towards correlation with tissue HBV S RNA and a significant correlation with core RNA levels. The results suggest that intrahepatic HBsAg might be a limiting factor for HDV particle secretion, but do not support the hypothesis that HDV suppresses HBV replication. •HBV RNA and HDV RNA levels in liver tissue varied between and within patients.•Tissue levels of HDV RNA were not associated with HBV core or S RNA.•This observation does not support repression of HBV replication by HDV.•Serum HDV RNA correlated with serum HBsAg and tended to correlate with tissue S RNA.•This observation suggests that the HBsAg supply might limit HDV virion production. The aim of this study was to investigate correlations between levels of intrahepatic HDV RNA, HBV RNA and corresponding serum markers in patients who underwent transplantation because of HDV-induced liver disease.BACKGROUNDThe aim of this study was to investigate correlations between levels of intrahepatic HDV RNA, HBV RNA and corresponding serum markers in patients who underwent transplantation because of HDV-induced liver disease.10 pieces of tissue from each of five liver explants from patients that underwent transplantation because of HDV-induced liver disease were analyzed by digital droplet PCR.METHODS10 pieces of tissue from each of five liver explants from patients that underwent transplantation because of HDV-induced liver disease were analyzed by digital droplet PCR.A large variation of the tissue levels of viral RNA was found both between and within patients. Overall, tissue levels of HBV core and S RNA were positively associated. However, no consistent association was observed between tissue levels of HDV RNA and either core or S RNA, except in one patient. Furthermore, intrahepatic HDV RNA levels did not correlate with serum HDV RNA. Instead, serum HDV RNA showed a positive correlation with serum HBsAg, a trend towards correlation with tissue HBV S RNA and a significant correlation with core RNA levels.RESULTSA large variation of the tissue levels of viral RNA was found both between and within patients. Overall, tissue levels of HBV core and S RNA were positively associated. However, no consistent association was observed between tissue levels of HDV RNA and either core or S RNA, except in one patient. Furthermore, intrahepatic HDV RNA levels did not correlate with serum HDV RNA. Instead, serum HDV RNA showed a positive correlation with serum HBsAg, a trend towards correlation with tissue HBV S RNA and a significant correlation with core RNA levels.The results suggest that intrahepatic HBsAg might be a limiting factor for HDV particle secretion, but do not support the hypothesis that HDV suppresses HBV replication.CONCLUSIONSThe results suggest that intrahepatic HBsAg might be a limiting factor for HDV particle secretion, but do not support the hypothesis that HDV suppresses HBV replication. The aim of this study was to investigate correlations between levels of intrahepatic HDV RNA, HBV RNA and corresponding serum markers in patients who underwent transplantation because of HDV-induced liver disease. 10 pieces of tissue from each of five liver explants from patients that underwent transplantation because of HDV-induced liver disease were analyzed by digital droplet PCR. A large variation of the tissue levels of viral RNA was found both between and within patients. Overall, tissue levels of HBV core and S RNA were positively associated. However, no consistent association was observed between tissue levels of HDV RNA and either core or S RNA, except in one patient. Furthermore, intrahepatic HDV RNA levels did not correlate with serum HDV RNA. Instead, serum HDV RNA showed a positive correlation with serum HBsAg, a trend towards correlation with tissue HBV S RNA and a significant correlation with core RNA levels. The results suggest that intrahepatic HBsAg might be a limiting factor for HDV particle secretion, but do not support the hypothesis that HDV suppresses HBV replication.
ArticleNumber	105871
Author	Nilsson, Staffan Strömberg, Lucia Gonzales Ringlander, Johan Andersson, Maria E. Rydell, Gustaf E. Stenbäck, Joakim Bedner Castedal, Maria Lindh, Magnus Skoglund, Catarina
Author_xml	– sequence: 1 givenname: Gustaf E. orcidid: 0000-0001-8093-2251 surname: Rydell fullname: Rydell, Gustaf E. email: gustaf.rydell@gu.se organization: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden – sequence: 2 givenname: Lucia Gonzales surname: Strömberg fullname: Strömberg, Lucia Gonzales organization: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden – sequence: 3 givenname: Johan orcidid: 0000-0002-8483-6504 surname: Ringlander fullname: Ringlander, Johan organization: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden – sequence: 4 givenname: Maria E. orcidid: 0000-0003-0005-7114 surname: Andersson fullname: Andersson, Maria E. organization: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden – sequence: 5 givenname: Catarina surname: Skoglund fullname: Skoglund, Catarina organization: The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden – sequence: 6 givenname: Joakim Bedner surname: Stenbäck fullname: Stenbäck, Joakim Bedner organization: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden – sequence: 7 givenname: Staffan surname: Nilsson fullname: Nilsson, Staffan organization: Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Sweden – sequence: 8 givenname: Maria surname: Castedal fullname: Castedal, Maria organization: The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden – sequence: 9 givenname: Magnus orcidid: 0000-0002-8729-7462 surname: Lindh fullname: Lindh, Magnus organization: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
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Cites_doi	10.1002/hep4.1507 10.1016/j.antiviral.2016.10.006 10.3390/pathogens13050362 10.1093/infdis/jiae045 10.1111/j.1365-2559.1992.tb00990.x 10.1111/apt.16807 10.1016/j.jhep.2023.01.005 10.1093/infdis/jiaa572 10.1128/jvi.63.10.4292-4297.1989 10.1111/jvh.13356 10.1016/j.jhep.2024.01.035 10.1016/j.jhep.2009.10.036 10.1111/jvh.12895 10.1002/hep4.1764 10.1126/scitranslmed.aan0241 10.1128/JVI.01609-10 10.1128/jvi.65.3.1099-1104.1991 10.1093/infdis/jiab469
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Keywords	ddPCR cccDNA nt HCC HBsAg HBV integration HDV HBV
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Snippet	The aim of this study was to investigate correlations between levels of intrahepatic HDV RNA, HBV RNA and corresponding serum markers in patients who underwent... Background: The aim of this study was to investigate correlations between levels of intrahepatic HDV RNA, HBV RNA and corresponding serum markers in patients...
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SubjectTerms	Adult Aged ddPCR Female HBV integration HCC HDV Hepatitis B Core Antigens - genetics Hepatitis B Surface Antigens - blood Hepatitis B Surface Antigens - genetics Hepatitis B virus - genetics Hepatitis D - complications Hepatitis D - virology Hepatitis Delta Virus - genetics Hepatitis Delta Virus - isolation & purification Humans Infectious Medicine Infektionsmedicin Liver - virology Liver Cirrhosis - virology Male Middle Aged RNA, Viral - analysis RNA, Viral - blood RNA, Viral - genetics Viral Load
Title	Large spatial variation of intrahepatic HDV RNA levels without association with HBV core or S RNA levels in HDV cirrhosis patients
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