Efficacy and Safety of Tenofovir Disoproxil Treatment for Chronic Hepatitis B Patients with Genotypic Resistance to Other Nucleoside Analogues: A Prospective Study.

BACKGROUND: Tenofovir disoproxil (TDF) is a promising salvage therapy for patients with chronic hepatitis B (CHB) who failed regimens of other nucleoside analogues (NAs). In this study, we aimed to investigate the clinical efficacy and safety of TDF monotherapy in Chinese CHB patients with genotypic resistance. METHODS: A total of 33 CHB patients who had failed treatment with other NAs and had genotypic resistance were switched to TDF monotherapy for 48 weeks. Patients' demographic data (age, sex, history of hepatitis B virus [HBV] therapy), laboratory testing results (hepatitis B e antigen [HBeAg] status, HBV DNA levels, alanine aminotransferase [ALT] levels, serum creatinine, urinary protein, genotypic assay), clinical symptoms, and liver color ultrasound examinations were collected for evaluation at day 0 (baseline) and the 12th, 24th, 36th, and 48th weeks after initiating treatment. Statistical analyses were carried out using rank sum test or rank correlation. RESULTS: With regard to efficacy, the study found that all patients who switched to TDF monotherapy had undetectable HBV DNA levels after 48 weeks. In addition, patients with lower baseline HBV DNA levels realized earlier virological undetectability (rs = 0.39, P = 0.030). ALT levels were normal in 30 of 33 patients (91%). HBeAg negative conversion occurred in 7 of 25 patients (28%), among whom HBeAg seroconversion (12%) and HBeAg seroclearance (16%) occurred. The time of complete virological response was significantly affected by the number of resistance loci (rs = 0.36, P = 0.040). Concerning safety, the study found that no adverse events were observed during the 48 weeks. CONCLUSION: TDF monotherapy is an effective and safe salvage treatment for CHB patients who are resistant to other NAs.

2-[3-Acetyl-5-(2-chloro-3-pyrid-yl)-2-methyl-2,3-dihydro-1,3,4-oxadiazol-2-yl]-4-fluoro-phenyl acetate.

In the title compound, C(18)H(15)ClFN(3)O(4), the dihedral angle between the substituted pyridine ring and the oxadiazo-line ring is 9.73 (19)° and the acyl group is coplanar with the oxadiazo-line ring [O-C-N-C torsion angle = -2.1 (3)°]. Furthermore, the substituted benzene ring is almost orthogonal with the oxadiazo-line ring, the dihedral angle between them being 87.56 (18)°.