Current treatment with nucleos(t)ide analogs (NUCs) safely controls the replication of hepatitis B virus (HBV) and improves prognosis in patients with HBV. However, the inability to completely clear HBV is problematic, and novel therapies are desired. It has been believed that all NUCs have similar functions to inhibit HBV reverse transcriptase. However, our recent findings that only acyclic nucleoside phosphonates (ANPs; adefovir dipivoxil and tenofovir disoproxil fumarate) had an additional effect of inducing interferon (IFN)‐λ3 in the gastrointestinal tract suggests that ANPs are not only distinct from nucleoside analogs (lamivudine and entecavir) in their structures but also in their functions. Because enteric lipopolysaccharide (LPS) can cross the intestine and affect peripheral blood mononuclear cells (PBMCs), we hypothesized that orally administered ANPs could have further additional effects to modulate LPS‐mediated cytokine profile in PBMCs.

中文翻译：

---

无环磷酸核苷治疗乙型肝炎病毒感染的免疫调节机制

目前使用核苷（酸）类似物 (NUC) 进行治疗可以安全地控制乙型肝炎病毒 (HBV) 的复制并改善 HBV 患者的预后。然而，无法完全清除HBV是有问题的，需要新的疗法。人们认为所有的 NUCs 都具有相似的抑制 HBV 逆转录酶的功能。然而，我们最近的研究结果表明，只有无环核苷膦酸酯（ANP；阿德福韦酯和富马酸替诺福韦二吡呋酯）具有在胃肠道中诱导干扰素（IFN）-λ3 的额外作用，这表明 ANP 不仅不同于核苷类似物（拉米夫定和恩替卡韦） ) 在它们的结构中，而且在它们的功能中。因为肠溶脂多糖（LPS）可以穿过肠道影响外周血单核细胞（PBMC），