Ababneh Nidaa A, Sallam Malik, Kaddomi Doaa, Attili Abdelrahman M, Bsisu Isam, Khamees Nadia, Khatib Amer, Mahafzah Azmi
Cell Therapy Center (CTC), University of Jordan, Amman, Jordan.
Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, University of Jordan, Amman, Jordan.
PeerJ. 2019 Mar 8;7:e6583. doi: 10.7717/peerj.6583. eCollection 2019.
Hepatitis B virus (HBV) is an important infectious cause of morbidity and mortality in Jordan. HBV genotype D is the most prevalent in the country. Virus escape mutants in the HBV region is an important public health problem halting preventive efforts. The aim of the current study was to investigate patterns of HBV escape and resistance mutations and to assess domestic transmission of the virus.
Patients infected with HBV were recruited at Jordan University Hospital ( = 56) and were diagnosed during (1984-2012). A total of 37 partial HBV sequences were generated using Sanger's method. Mutation analysis was done using the HIV grade HBV drug resistance interpretation online tool and Geno2pheno (HBV) online tools. Domestic transmission of HBV was assessed using maximum likelihood phylogenetic inference with similar GenBank sequences.
Genotyping revealed an exclusive presence of sub-genotype D1. Typical HBV escape mutants were identified in seven patients. These mutations included: L109R, Q129R, M133L, S143L and D144E with overall prevalence of 18.9% (95% CI [9.5-34.2]). Reverse transcriptase (RT) sequence analysis showed mutations in three patients with overall prevalence of 8.1% (95% CI [2.8-21.3]). RT mutations included: V173L, S202I, L180M, M204V and T184A. Transmission cluster analysis revealed a relatively high proportion of infections taking place as a result of domestic spread (29.7%).
Based on our findings, RT mutation analysis appears to be of high value before the initiation of therapy in patients with chronic HBV infection in Jordan. Phylogenetic analyses revealed a considerable proportion of local spread in the country which should be considered in the preventive infection control efforts.
乙型肝炎病毒（HBV）是约旦发病和死亡的重要感染原因。HBV D基因型在该国最为普遍。HBV区域的病毒逃逸突变体是阻碍预防工作的一个重要公共卫生问题。本研究的目的是调查HBV逃逸和耐药突变模式，并评估该病毒的家庭传播情况。
在约旦大学医院招募了感染HBV的患者（n = 56），并于1984年至2012年期间进行诊断。使用桑格法共生成了37个部分HBV序列。使用HIV等级HBV耐药性解释在线工具和Geno2pheno（HBV）在线工具进行突变分析。使用具有相似GenBank序列的最大似然系统发育推断评估HBV的家庭传播情况。
基因分型显示仅存在D1亚型。在7名患者中鉴定出典型的HBV逃逸突变体。这些突变包括：L109R、Q129R、M133L、S143L和D144E，总体患病率为18.9%（95%CI[9.5 - 34.2]）。逆转录酶（RT）序列分析显示3名患者存在突变，总体患病率为8.1%（95%CI[2.8 - 21.3]）。RT突变包括：V173L、S202I、L180M、M204V和T184A。传播聚类分析显示，家庭传播导致的感染比例相对较高（29.7%）。
根据我们的研究结果，对于约旦慢性HBV感染患者，在开始治疗前进行RT突变分析似乎具有很高的价值。系统发育分析显示该国存在相当比例的本地传播，在预防性感染控制工作中应予以考虑。
