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World J Gastroenterol. 2016 Mar 21; 22(11): 3165–3174.
Published online 2016 Mar 21. doi: 10.3748/wjg.v22.i11.3165
PMCID: PMC4789991
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, and 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.
Correspondence to: Javier García-Samaniego, MD, PhD, Hepatology Section, Gastroenterology Department, Hospital Universitario La Paz, CIBERehd, Paseo de la Castellana 261, 28046 Madrid, Spain. ten.acinofelet@ogeinamasreivaj
Telephone: +34-91-4532510 Fax: +34-91-7336614
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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.
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发表于 2016-4-7 16:27
