Infectious and Tropical Diseases Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.
Nurexbiotech, University Hospital of Sassari, Sassari, Italy.
Sci Rep. 2020 Feb 6;10(1):2014. doi: 10.1038/s41598-020-58837-3.
Our study purpose was to evaluate mitochondrial (mt)DNA and RNA in peripheral blood mononuclear cells (PBMCs) and body shape changes (BSC) in HBV-infected patients. mtDNA and mtRNA were measured in PBMCs. The presence of BSC was evaluated through a questionnaire and clinical evaluation. A total of 157 subjects were enrolled, of these 107 were HBV-infected patients, 54 receiving nucleoside analogues (NAs, Group A), 53 naive to antivirals (Group B) and 50 age-sex matched controls (Group C). All HBV-treated patients had negative HBV-DNA. Twenty (37,0%) received lamivudine + adefovir, 20 (37.0%) tenofovir, 2 (3.7%) lamivudine and 12 (22.2%) entecavir. Therapy median duration was 38 months (IQR 20-60) in NA-treated patients. Group A showed significantly higher mtDNA/nuclear (n) DNA ratio (p = 0.000008) compared to Group C and Group B (p = 0.002). Group B showed significantly higher mtDNA/nDNA ratio compared to Group C (p = 0.017). Group A and B had significantly lower mtRNA/nRNA ratio compared to Group C (p = 0.00003 and p = 0.00006, respectively). Tenofovir and entecavir showed less impact compared to lamivudine + adefovir. mtDNA/nDNA ratio positively (Rho = 0.34, p < 0.05) and mtRNA/nRNA ratio negatively (Rho = -0.34, p < 0.05) correlated with therapy duration. BSC were significantly more frequent in Group A [10/54 (18.5%)] compared to Group B [3/53 (5.6%, p = 0.04)] and Group C [0/50, (p = 0.0009)]. In conclusion, long-term NA therapy was associated both to mitochondrial toxicity and BSC, showing significant differences in mtDNA and mtRNA levels. Tenofovir and entecavir showed lower impact on alterations, compared to 1 generation NA.
我们的研究目的是评估乙型肝炎病毒（HBV）感染者外周血单个核细胞（PBMC）中的线粒体（mt）DNA 和 RNA 以及身体形态变化（BSC）。在 PBMC 中测量 mtDNA 和 mtRNA。通过问卷调查和临床评估评估 BSC 的存在。共纳入 157 例受试者，其中 107 例为 HBV 感染者，54 例接受核苷类似物（NA）治疗（A 组），53 例为抗病毒药物初治者（B 组），50 例年龄和性别匹配的对照组（C 组）。所有 HBV 治疗患者的 HBV-DNA 均为阴性。20 例（37.0%）接受拉米夫定+阿德福韦酯，20 例（37.0%）接受替诺福韦，2 例（3.7%）接受拉米夫定，12 例（22.2%）接受恩替卡韦。NA 治疗患者的治疗中位时间为 38 个月（IQR 20-60）。与 C 组和 B 组相比，A 组的 mtDNA/核（n）DNA 比值明显更高（p=0.000008），与 C 组相比，B 组的 mtDNA/nDNA 比值明显更高（p=0.002）。与 C 组相比，A 组和 B 组的 mtRNA/nRNA 比值明显更低（p=0.00003 和 p=0.00006）。与拉米夫定+阿德福韦酯相比，替诺福韦和恩替卡韦的影响较小。mtDNA/nDNA 比值呈正相关（Rho=0.34，p<0.05），mtRNA/nRNA 比值呈负相关（Rho=-0.34，p<0.05）与治疗持续时间相关。与 B 组（53 例中有 3 例，5.6%，p=0.04）和 C 组（50 例中均无）相比，A 组（54 例中有 10 例，18.5%）BSC 的发生率明显更高（p=0.0009）。结论：长期接受 NA 治疗与线粒体毒性和 BSC 相关，mtDNA 和 mtRNA 水平存在显著差异。与第一代 NA 相比，替诺福韦和恩替卡韦的影响较小。
