Long-term TDF ‘promising’ in Chinese HBV patients after multiple antiviral failures

Feb 18 2015

By Shreeya Nanda, Senior medwireNews Reporter

Long-term tenofovir disoproxil fumarate (TDF) therapy is effective in Chinese patients with chronic hepatitis B virus (HBV) infection who have relapsed after treatment with multiple nucleos(t)ide analogues, research suggests.

In this prospective study, the “first” such in Chinese patients, 115 patients who had previously failed two or more nucleos(t)ide analogue treatments were given TDF 300 mg daily for at least 72 weeks, report Jia Xiao (Shenzhen Third People’s Hospital) and co-workers in Hepatology Research.

Complete viral response (CVR), defined as HBV DNA level below 100 IU/mL, was achieved by 57.4%, 69.6%, 74.8% and 86.1% of patients at 12, 24, 48 and 72 weeks of treatment, respectively.

And at 72 weeks, 23.2% of patients showed seroclearance of hepatitis B e-antigen (HBeAg) and 77.3% normalisation of alanine aminotransferase (ALT) levels.

There was also a significant decrease in the level of hepatitis B surface antigen (HBsAg), from 3.78 log₁₀ IU/mL before TDF therapy to 3.03 log₁₀ IU/mL after completion.

Rates of CVR, HBeAg clearance and HBsAg reduction were similar between the 76 participants with and the 39 participants without drug-resistance mutations. But ALT normalisation rates at 12 and 72 weeks were significantly lower in patients with lamivudine-resistant mutations (n=49) compared with those without any mutations.

Moreover, individuals with dual resistance to lamivudine and adefovir had significantly lower CVR rates after 72 weeks than patients resistant to only one of the drugs, the team reports, adding that “TDF monotherapy may not be enough for patients with multiple mutations, which need further antiviral therapies.”

Xiao et al say that the treatment was well tolerated, and estimated glomerular filtration rates (eGFR) at 72 weeks did not decline by more than 20% from the baseline in any patient. But they did observe a decreasing trend of eGFR values during the course of treatment and identified four patients who had an eGFR of less than 80 mL/min per 1.73 m², prompting them to highlight the importance of monitoring eGFR during TDF treatment.

The researchers conclude that “TDF may serve as a promising agent against HBV infection clinically” given its potent antiviral effects and good tolerability.

“Indeed, a randomized double-blind placebo-controlled multicenter clinical trial of the long-term efficacy and safety of TDF therapy in [chronic hepatitis B] patients is warranted to further investigate its application.”

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