Summary from virtual CROI 2022 for HIV and liver disease
Hepatitis elimination for 2030 on track?
Is fatty liver disease a growing concern?
New insights from CROI 2022.
Jurgen K. Rockstroh M.D., Professor of Medicine
University of Bonn, Germany
Correspondence:
Prof. Dr. Jurgen K. Rockstroh
Department of Medicine I
University Hospital Bonn
Venusberg-Campus 1
53127 Bonn
Germany
Extract:
"Overall, hardly any data was presented on new HBV treatment agents. Of note, however was an animal study which reported on a nanoformulated tenofovir (TFV) prodrug which was able to suppress HBV DNA in humanized and transgenic mice for three months following a single intramuscular injection (6). For this study a lipophilic TFV prodrug, M1TFV, was synthesized and nanoformulated into stable poloxamer 407 stabilized aqueous nanocrystals (NM1TFV) by high pressure homogenization. Solid drug nanocrystals of TAF (NTAF) were produced and used as controls. Formulation efficacy was evaluated in two mouse models (HBV-infected humanized liver TK-NOG mice and HBV transgenic Tg05 mice) following a single intramuscular injection of 168 mg/kg TFV equivalents of either NM1TFV or NTAF. HBV DNA levels in peripheral blood were assessed biweekly for 12 weeks. HBV markers HBcAg and HBsAg were evaluated on stained liver sections of TK-NOG mice. Drug levels were quantified by mass spectrometry. A single intramuscular injection of NM1TFV to HBV infected humanized TK-NOG mice suppressed viral DNA in peripheral blood and liver for three months. Levels of HBcAg and HBsAg were equally suppressed over three months in NM1TFV treated mice. Overall, NM1TFV formulations were well tolerated and no evidence of muscle degeneration, basophil or eosinophil infiltration, cellulitis or abscesses were observed at the injection site. The authors conclude that NM1TFV can be developed as a therapy for chronic HBV infection. Just as in other medical areas development of long-acting treatment options could be of considerable interest in HBV patients who require potentially lifelong treatment of chronic HBV infection and are facing adherence challenges. "作者: StephenW 时间: 2022-9-18 22:23
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933441/
Front Immunol. 2021; 12: 638447.
Published online 2021 Feb 19. doi: 10.3389/fimmu.2021.638447
PMCID: PMC7933441
PMID: 33679796 Establishment of Humanized Mice for the Study of HBV
Fritz Lai,1,2,* Cherry Yong Yi Wee,1 and Qingfeng Chen1,3,4,*
"It was only until recently when recombinant HBV cccDNA was successfully generated in mice injected hydrodynamically through Cre-/Loxp-mediated recombination which functions similarly to real HBV cccDNA in the production of mature viruses (14, 25). More importantly, the improved stability and persistence of HBV severely damaged mice livers for the very first time which resulted in advanced liver pathogenesis evidenced by development of fibrosis (26). Although transgenic mice exhibiting such phenotype was considered a major breakthrough in the field of HBV in vivo, the study still revolved around a complete mouse host setting. Since human hepatocytes are the natural cellular target of HBV, the inevitable transition of mouse to human eventually gave rise to various establishments of human liver chimeric mice."