Hepatitis B is a liver infection caused by the hepatitis B virus (HBV), and long-term hepatitis B infections that last longer than six months are considered “chronic.” Chronic hepatitis B (CHB) poses a huge health care burden as it is a common cause of chronic liver disease and is also associated with the development of liver cirrhosis and liver cancer.

The antiviral tenofovir disoproxil fumarate (TDF) is currently the most widely used treatment for CHB. However, long-term treatment with TDF causes a gradual decrease in kidney function and bone health, making it necessary to explore safer long-term treatment options.

Besifovir dipivoxil maleate (BSV) is another drug that has been shown to have an antiviral efficacy comparable to TDF in a stage 3 clinical trial, with improved kidney and bone safety in treated patients. However, this study was done on individuals who had never received treatment for CHB—in the real world, most patients with CHB are already being treated with TDF, possibly for several years.

To address this limitation, a multicenter research team led by Dr. Hyung Joon Yim from the Department of Internal Medicine, Korea University Ansan hospital, Korea has studied the effects of switching from long-term TDF to the antiviral BSV in patients with CHB, as part of a stage 4 clinical trial. In a study published online on 16 January 2025 in Clinical and Molecular Hepatology, they enrolled 153 patients with CHB who were receiving TDF treatment for 48 weeks or more. These patients were then randomly chosen to receive either BSV or TDF for another 48 weeks.

The first aim in this study was to confirm that BSV was not inferior to TDF in terms of antiviral efficacy. This was tested by measuring the amount of HBV DNA in the patients’ blood. Among all the patients who completed their allocated treatment, the study found that 100% and 98.5% of patients receiving BSV and TDF respectively showed a virologic response against HBV, with very low virus levels not to be detected in the blood by sensitive assay.

“We also noted no antiviral resistance after switching from TDF to BSV,” adds Dr. Yim.

More importantly, the researchers showed that patients who switched to BSV showed, on average, a higher percentage of change in a parameter called estimated glomerular filtration rate, which indicates improved kidney functioning. The group treated with BSV also had higher hip and spine bone density, indicating improved bone strength.

“These results show that adverse effects of long-term TDF may be potentially reversible with improved kidney function and bone density after switching to BSV,” says Dr. Yim, highlighting the potential of BSV as a safer long-term therapy for hepatitis B. “It seems that long term treatment with BSV would be a viable option for patients with CHB,” he adds. These findings offer new hope for patients undergoing long-term antiviral treatment for hepatitis B.

Provided by
Korea University College of Medicine