High rates of chronic HBV genotype E infection in a group of migrants in Italy from West Africa: Virological characteristics associated with poor immune clearance
High rates of chronic HBV genotype E infection in a group of migrants in Italy from West Africa: Virological characteristics associated with poor immune clearance
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DOI：
10.1371/journal.pone.0195045
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发表时间：
2018-03-29
期刊：
影响因子：
3.7
通讯作者：
Sarmati, Loredana
中科院分区：
文献类型：
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作者：
Malagnino, Vincenzo;Salpini, Romina;Sarmati, Loredana
B型肝炎病毒（HBV）基因型E几乎只发生在非洲人中，其存在更常与慢性HBV（CH B）感染的发展相关。此外，已发现HBV基因型E感染的分布与肝细胞癌高发的非洲国家之间存在流行病学联系。作为移民健康评估项目的一部分，我们评估了358名年轻的非洲受试者的HBV感染情况; 58.1%（208/358）的HBV标志物呈阳性，54名（25.5%）患有CHB。81%的CHB受试者感染HBV基因型E，血清HBV-DNA中位数为3.2（IQR：2.7-3.6）logIU/ml。所有患者血清HBsAg滴度均较高（10，899 [范围5，359 - 20，272] IU/ml），未发现HBsAg滴度与HBV-DNA血浆水平之间存在相关性。RT序列分析显示存在许多免疫逃逸突变：所有患者的菌株在HBsAg位置140处具有丝氨酸; 3个还具有T116 N、Y100 C和P142 L + S143 L置换; 1个具有G112 R置换。6例（18%）患者在第216位有终止密码子。在9例CHB患者中的5例（26.5%）中，进行了超声肝活检、肝内总HBV-DNA和cccDNA定量以及RT/HBsAg测序。中位（IQR）总肝内HBV-DNA为766（753-1139）拷贝/1000个细胞，中位（IQR）cccDNA为17（10- 27）拷贝/1000个细胞。肝内总HBV-DNA和cccDNA均与血清HBV-DNA相关，而HBsAg滴度无相关性。在从血浆和肝组织获得的HBsAg序列中发现2.5/1，000个核苷酸的差异，其中3例可能存在病毒解剖学区室化。总之，在一组来自西非的移民中，由于E基因型，CHB感染率很高。对获得的病毒株的分析显示了免疫逃逸的病毒学特征，这可能是病毒复制持续的原因。此外，还发现了相当比例的终止密码子突变。这些受试者中发现的HBsAg滴度与血浆或肝内HBV-DNA之间缺乏相关性，表明病毒产生途径与HBsAg分泌无关。建议对大量E基因型CHB患者进行研究，以证实这些观察结果。
Hepatitis B virus (HBV) genotype E almost exclusively occurs in African people, and its presence is more commonly associated with the development of chronic HBV (CHB) infection. Moreover, an epidemiological link has been found between the distribution of HBV genotype E infection and African countries with high incidences of hepatocellular carcinoma. As part of a programme for the health assessment of migrants, we evaluated 358 young African subjects for HBV infection; 58.1% (208/358) were positive for an HBV marker, and 54 (25.5%) had CHB. Eighty-one percent of the CHB subjects were infected with HBV genotype E, with a median serum HBV-DNA of 3.2 (IQR: 2.7-3.6) logIU/ml. All patients had high serum HBsAg titres (10,899 [range 5,359-20,272] IU/ml), and no correlation was found between HBsAg titres and HBV-DNA plasma levels. RT sequence analysis showed the presence of a number of immune escape mutations: strains from all of the patients had a serine at HBsAg position 140; 3 also had T116N, Y100C, and P142L + S143L substitutions; and 1 had a G112R substitution. Six (18%) patients had stop-codons at position 216. In 5 of the 9 (26.5%) CHB patients, ultrasound liver biopsy, quantification of total intrahepatic HBV-DNA and cccDNA, and RT/HBsAg sequencing were performed. The median (IQR) total intrahepatic HBV-DNA was 766 (753-1139) copies/1000 cells, and the median (IQR) cccDNA was 17 (10- 27) copies/1000 cells. Correlations were observed for both total intra-hepatic HBV-DNA and cccDNA with serum HBV-DNA, while no correlation was found for the HBsAg titres. A difference of 2.5/1,000 nucleotides was found in the HBsAg sequences obtained from plasma and from liver tissue, with 3 cases of possible viral anatomical compartmentalization. In conclusion, a high rate of CHB infection due to the E genotype was demonstrated in a group of immigrants from Western Africa. An analysis of the viral strains obtained showed the virological characteristics of immune escape, which may be the cause of viral replication persistence. Moreover, a fair percentage of stop codon mutations were found. The lack of correlation between HBsAg titres and plasma or intrahepatic HBV-DNA found in these subjects suggests a pathway of virus production that is not linked to HBsAg secretion. Studies with a larger number of patients with CHB due to the E genotype are advisable to corroborate these observations.