Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2016; 22(11): 3165-3174
Published online Mar 21, 2016. doi: 10.3748/wjg.v22.i11.3165
Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype
Antonio Madejón, Míriam Romero, Ángela Hernández, Araceli García-Sánchez, Marta Sánchez-Carrillo, Antonio Olveira, Javier García-Samaniego
Antonio Madejón, Míriam Romero, Ángela Hernández, Araceli García-Sánchez, Marta Sánchez-Carrillo, Antonio Olveira, Javier García-Samaniego, Hepatology Section, Gastroenterology Department, Hospital Universitario La Paz, 28046 Madrid, Spain
Antonio Madejón, Míriam Romero, Ángela Hernández, Araceli García-Sánchez, Marta Sánchez-Carrillo, Antonio Olveira, Javier García-Samaniego, Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas (CIBERehd), 28046 Madrid, Spain
Antonio Madejón, Míriam Romero, Ángela Hernández, Araceli García-Sánchez, Marta Sánchez-Carrillo, Antonio Olveira, Javier García-Samaniego, Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain
Author contributions: Madejón A and García-Samaniego J designed research; Romero M, García-Sánchez A, Olveira A and García-Samaniego J performed clinical research and analyzed clinical data; Madejón A, Hernández A and Sánchez-Carrillo M performed basic research and analyzed experimental data; Madejón A and García-Samaniego J wrote the paper; all authors contributed to the revision of the final version of the paper.
Supported by A grant from the “Fondo de Investigaciones Sanitarias” (FIS: PI081486), of the “Ministerio de Ciencia e Innovación” of Spain, with FEDER funds; and CIBERehd is funded by the “Instituto de Salud Carlos III”.
Institutional review board statement: This work was approved by the Ethical Committee (CEIC), and the Scientific Committee of Hospital Carlos III, Madrid, Spain.
Conflict-of-interest statement: The authors who have taken part in this study declare that they have nothing to disclose regarding funding or conflict of interest with respect to this manuscript.
Data sharing statement: Participants gave informed consent for its inclusion in the study; the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Javier García-Samaniego, MD, PhD, Hepatology Section, Gastroenterology Department, Hospital Universitario La Paz, CIBERehd, Paseo de la Castellana 261, 28046 Madrid, Spain. javiersamaniego@telefonica.net
Telephone: +34-91-4532510 Fax: +34-91-7336614
Received: September 25, 2015
Peer-review started: September 28, 2015
First decision: October 14, 2015
Revised: November 4, 2015
Accepted: January 17, 2016
Article in press: January 17, 2016
Published online: March 21, 2016
Processing time: 170 Days and 14.8 Hours
Abstract

AIM: To study the hepatitis B virus (HBV) and hepatitis D virus (HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV genotypes.

METHODS: We conducted a transversal study including 68 chronic hepatitis delta (CHD) (37 HIV-positive) patients and a control group of 49 chronic hepatitis B (CHB) (22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B (HBsAg) serum titers were analyzed with the Monolisa HBsAg Ultra system (Bio-Rad), using as quantification standard a serial dilution curve of an international HBsAg standard. Serum HBV-DNA titers were analyzed using the Roche Cobas TaqMan (Roche, Barcelona, Spain), and the serum HDV-RNA using an in-house real-time qRT-PCR method, with TaqMan probes. HBV genotype was determined with the line immunoassay LiPA HBV genotyping system (Innogenetics, Ghent, Belgium). In those patients negative for LiPA assay, a nested PCR method of complete HBsAg coding region, followed by sequence analysis was applied.

RESULTS: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median (IQR): 1.25 (1.00-1.35) vs 2.95 (2.07-3.93) log10 (copies/mL), P = 0.013] and HIV positive patients [2.63 (1.24-2.69) vs 7.25 (4.61-7.55) log10 (copies/mL), P < 0.001]. This was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with LiPA assay. Finally, the HBsAg titers reflected no significant differences in CHD patients infected with HBV-A or D.

CONCLUSION: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E.

Keywords: Hepatitis D virus; Hepatitis B virus; Delta hepatitis; Replication interference; Viral replication

Core tip: Hepatitis B virus (HBV)-DNA titer is a predictive pattern of optimal response to treatment with interferon based regimens. Our results suggest that in chronic hepatitis delta patients the inhibition of HBV replication is genotype-dependent. Viral replication interference between HBV and hepatitis B virus (HDV) is more evident in patients infected with HBV-genotype A, than with HBV-D or E. Based on these results the analysis of HBV genotype could be taken into account in the algorithms for treatment indication for delta infected patients. For patients from geographical regions with a different distribution of HBV genotypes, the replication behaviour of HBV is warranted to clarify the HBV/HDV interference process.