Major hydrophilic region in genomic HBV extending from aa99 to aa169, clustered with a highly conformational epitope, is critical to the antigenicity of hepatitis B surface antigen (HBsAg) and may affect the diagnosis of HBV in HBV screening test. So, this study aimed to characterize variants of S gene product of hepatitis B virus (HBV) isolated from patients with overt or occult HBV infection in north-eastern Egypt. The study included sera of two different groups of volunteer blood donors (VBDs), 82 with overt HBV that were positive for HBsAg and anti-HBc and 343 donors negative for HBsAg eligible for donation. Of the latter group, only 44 were positive for anti-HBc. All anti-HBc positive sera were subjected to HBV DNA detection and partial sequence analysis targeting the HBV S gene. HBV DNA was detected in 22.7 % of HBsAg-/anti-HBc + (10/44 patients) and in 90 % of HBsAg + donors (74/82 patients) with significant statistical difference (P = 0.0001). Phylogenetic analysis showed that HBV strains retrieved from both groups were of genotype D. Amino acid escape mutation T125M was detected in only 2 samples of the occult infection group and in none of the overt group (P = 0.01). Different amino acid substitutions were identified in overt infection group: S143L/T (16.2 %, 12/74) and P120T/S (2.7 %, 2/74). Q129R was significantly more frequent in cases with occult HBV infection (40 %, 4/10) than overt group (6.8 %, 5/74) (P = 0.01). HBV genotype D predominated both in patients with overt and occult HBV infection. Different profiles of amino acid substitutions in the major hydrophilic region were seen in these two groups in Egypt.

Hepatitis B virus (HBV) specifically infects human hepatocytes and increases the risks of cirrhosis and liver cancer. Currently, nucleic acid analogs are the main therapeutics for chronic hepatitis caused by HBV infection. Although nucleic acid analogs can eliminate HBV DNA by inhibiting HBV reverse transcriptase, they cannot lead to negative conversion of covalently closed circular DNA (cccDNA) and hepatitis B surface antigen (HBsAg). In this study, we revealed that the antifilarial drug ivermectin suppresses HBV production by a different mechanism from the nucleic acid analog entecavir or Na⁺ taurocholate co-transporting polypeptide-mediated entry inhibitor cyclosporin A. Ivermectin reduced the levels of several HBV markers, including HBsAg, in HBV-infected human hepatocellular carcinoma cells (HepG2-hNTCP-C4 cells) and humanized mouse hepatocytes (PXB hepatocytes). In addition, ivermectin significantly decreased the expression of HBV core protein and the nuclear transporter karyopherin α2 (KPNA2) in the nuclei of HepG2-hNTCP-C4 cells. Furthermore, depletion of KPNA1–6 suppressed the production of cccDNA. These results suggest that KPNA1–6 is involved in the nuclear import of HBV and that ivermectin suppresses the nuclear import of HBV by inhibiting KPNA2. This study demonstrates the potential of ivermectin as a novel treatment for hepatitis B.

症例は2歳男児．母と姉と祖母がB型肝炎ウイルス（HBV）キャリアで，母と姉はHBe抗原陽性かつ高HBV DNA量（HBV DNA＞7 log IU/ml）だった．出生直後に抗HBsヒト免疫グロブリンが投与され，HBワクチンが出生時，生後1，6カ月時に接種された．1歳時にHBs抗原陰性，HBs抗体333.8 mIU/mlだったが，2歳時にHBs抗原0.25 IU/ml，HBs抗体115.6 mIU/ml，HBV DNA 3.5 log IU/mlとHBV感染が成立した．直接シークエンス法による遺伝子解析により，本児，母，姉由来のHBVにワクチンエスケープ変異として知られるG145R変異とP120Q変異を認めた．母と姉が保有していた変異株が1歳以降に本児に水平感染したと考えられた．高ウイルス量HBVキャリア妊婦から出生した児では，2歳以降も継続的なフォローアップと積極的なワクチン追加接種も考慮する必要があると考えられた．