A major advance in hepatitis B treatment
Hepatitis B virus (HBV) is transmitted in similar ways to HIV and hepatitis C virus (HCV). HBV infects the liver and causes inflammation. Over time, healthy liver tissue is replaced with scar tissue. The presence of scar tissue greatly increases the risk for complications, liver failure and liver cancer.
The use of antiviral drugs (nucleoside/nucleotide analogues) such as TAF (tenofovir alafenamide), TDF (tenofovir DF) or entecavir is the mainstay of HBV treatment in Canada and many high-income countries today. These drugs help suppress the production of new copies of HBV and reduce the synthesis of proteins by HBV-infected cells. The net effect is that chronic HBV infection becomes a manageable condition. People with HBV can generally live long, healthy lives provided they continue to take these medicines every day. The vast majority of people with chronic HBV will require life-long therapy. Depending on the degree of liver injury (scar tissue), some people with chronic HBV will need additional monitoring so that doctors can stay abreast of the risk of liver cancer.
A functional cure
With current technology, it is unlikely that scientists can eliminate every HBV-infected cell—resulting in a cure—in the liver of people with chronic HBV.
In the meantime, several pharmaceutical companies are developing potential therapies that can effect what scientists call a “functional cure.” With a functional cure, researchers hope to eradicate the vast majority of HBV-infected cells in the liver. The residual level of HBV-infected cells is expected to be so low that the virus is likely controlled by the immune system and poses little risk to people. Furthermore, a functional cure should allow people to discontinue daily nucleoside/nucleotide therapy.
In theory, by removing the bulk of HBV-infected cells in people who are taking anti-HBV drugs, a functional cure should help reduce the risk of liver cancer that can arise due to chronic HBV.
A breakthrough for people with HBV
In an important development, doctors and scientists with the pharmaceutical company GSK (formerly GlaxoSmithKline) announced that the experimental drug bepirovirsen (commonly called “bepi” by researchers), which has activity against HBV, was able to effect a functional cure in about 20% of participants with chronic HBV in two clinical trials. That is, bepi suppressed HBV infection and reduced the burden of HBV-infected cells in the liver. It is possible that tiny amounts of HBV remained in the liver; however, the levels were sufficiently low that the immune system could control it.
It is worth stating again: The effect of bepi was so profound that approximately 20% of participants no longer had blood test results indicative of chronic HBV infection after discontinuing the drug.
This is a major advance, as rates of functional cure with previous therapies have been extremely low.
There is still much that needs to be understood about bepi and the profile of patients with chronic HBV who can benefit from it. Details about the future of bepi appear later in this issue of TreatmentUpdate. In the next article, we focus on the clinical trials in which bepi showed promising results.
—Sean R. Hosein
REFERENCES:
- Hou J, Lim SG, Buti M. Phase 3 results of bepirovirsen treatment for chronic hepatitis B virus infection. New England Journal of Medicine. 2026 Jun 25;394(24):2395-2406.
- Lok AS. A major step toward a cure for hepatitis B infection. New England Journal of Medicine. 2026 Jun 25;394(24):2471-2472.