Tenofovir disoproxil fumarate for multiple nucleos(t)ide analogues treatment failure hepatitis B: Is monotherapy enough?

作者：Liang, Xieer; Xie, Qing; Shang, Jia; Tang, Hong; Xu, Min; Meng, Qinghua; Zhang, Jiming; Gao, Pujun; Sheng, Jifang; Wang, Hao; Jia, Jidong; Wang, Guiqiang; Wu, Shunquan; Ping, Jingna; Hou, Jinlin^*

来源：Journal of Gastroenterology and Hepatology, 2022, 37(3): 471-479.

DOI：10.1111/jgh.15757

• antiviral resistance
• China
• efficacy
• hepatitis B e antigen
• hepatitis B surface antigen
• hepatitis B virus
• hepatitis B virus resistance
• multidrug-resistance
• safety
• virological response

Background and Aim Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs). Methods Patients included were aged 18-65 years, with treatment failure with multiple NAs (serum HBV DNA > 200 IU/mL after more than two different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA Overall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 log(10) IU/mL), with 77.0% patients (95% confidence interval: 71.1, 82.9) achieving serum HBV DNA < 20 IU/mL. Three (1.4%) patients experienced virological breakthrough during TDF monotherapy, without hepatitis flare. At Week 144, 15.3% and 4.7% patients (hepatitis B e antigen [HBeAg]-positive at baseline) experienced HBeAg loss and HBeAg seroconversion, respectively; 68.3% patients achieved normalized alanine aminotransferase levels. Overall, 58.7% patients experienced more than one adverse event (AE). Most common AEs were upper respiratory tract infection and blood creatine phosphokinase increase; 8.5% patients experienced study drug-related AEs; 9.4% patients experienced serious AEs (none were TDF-related). Among renal safety parameters, overall trend of mean serum phosphorous level remained stable, while mean estimated glomerular filtration rate increased slightly. Conclusions Tenofovir disoproxil fumarate monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.

• 单位
  浙江大学; 北京大学; 南方医科大学; 四川大学; 吉林大学; 复旦大学