乙型肝炎病毒与丁型肝炎病毒复制干扰：乙型肝炎病毒基因型的影响

Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype.

作者信息

Madejón Antonio, Romero Míriam, Hernández Ángela, García-Sánchez Araceli, Sánchez-Carrillo Marta, Olveira Antonio, García-Samaniego Javier

机构信息

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.

出版信息

World J Gastroenterol. 2016 Mar 21;22(11):3165-74. doi: 10.3748/wjg.v22.i11.3165.

DOI:10.3748/wjg.v22.i11.3165

PMID:27003993

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4789991/

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.

摘要

目的

研究感染不同乙肝病毒（HBV）基因型的慢性丁型肝炎患者中HBV和丁型肝炎病毒（HDV）的复制干扰情况。

方法

我们进行了一项横断面研究，纳入68例慢性丁型肝炎（CHD）患者（37例HIV阳性）和一个由49例慢性乙型肝炎（CHB）患者（22例HIV阳性）组成的对照组。此外，对16例CHD患者进行了动态随访。在所有样本中，使用Monolisa HBsAg Ultra系统（伯乐公司）分析乙肝表面抗原（HBsAg）血清滴度，将国际HBsAg标准品的系列稀释曲线作为定量标准。使用罗氏Cobas TaqMan（罗氏公司，西班牙巴塞罗那）分析血清HBV-DNA滴度，使用自行设计的实时定量逆转录聚合酶链反应（qRT-PCR）方法及TaqMan探针分析血清HDV-RNA。采用线性免疫分析LiPA HBV基因分型系统（英诺基因公司，比利时根特）确定HBV基因型。对于LiPA检测为阴性的患者，应用巢式PCR方法扩增完整的HBsAg编码区，随后进行序列分析。

结果

感染不同HBV基因型的CHB患者的HBV-DNA水平无差异。然而，在CHD患者中，感染HBV-A型的患者的HBV-DNA水平低于感染HBV-D型的患者，在HIV阴性患者中[中位数（四分位间距）：1.25（1.00 - 1.35）对2.95（2.07 - 3.93）log10（拷贝/毫升），P = 0.013]以及HIV阳性患者中[2.63（1.24 - 2.69）对7.25（4.61 - 7.55）log10（拷贝/毫升），P < 0.001]均如此。这在对HBV/HDV患者的动态研究中得到了证实。这些差异导致用LiPA检测分析的CHD患者中HBV-A型感染率被低估。最后，感染HBV-A型或D型的CHD患者的HBsAg滴度无显著差异。