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Functional Cure for Hepatitis B
Bridging the Gap to a Functional Cure for Hepatitis B

Released: April 21, 2025

Expiration: April 20, 2026

Su Wang
Su Wang, MD, MPH, FACP
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Key Takeaways
  • Use of a quantitative HBsAg allows healthcare professionals to monitor disease activity in the liver, including people receiving antivirals with undetectable HBV DNA in the bloodstream.
  • A functional cure, or sustained loss of HBsAg and undetectable HBV DNA, would be life-changing for many people by reducing liver disease progression and concern for transmission—potentially dispelling some HBV-associated stigma.
  • As we await the development of HBV therapies that provide a functional cure, our approach with current therapies are shifting to offering more people antivirals earlier using shared decision-making.

We think of hepatitis B virus (HBV) as a liver disease, but it affects multiple dimensions of a person’s life. The psychosocial burden on people living with chronic hepatitis B (CHB) can actually be greater than the physical manifestations from the disease. 

Many individuals worry a great deal about developing liver cancer or transmitting the virus to others, and it can impact how they see themselves and how they interact with others. CHB becomes a stressor, and many feel they cannot be in a relationship because of having to divulge their status.

In countries where there has been discrimination, there are countless stories from people living with CHB describing that their education and careers were cut short and their worlds came crashing down because of having CHB.

The Dream of a Functional Cure
We have a lot of hope in emerging HBV therapies that may provide patients with better control of the virus and even a functional cure. The community has been waiting for therapies that can lead to a loss of HBsAg (and undetectable HBV DNA), the definition of functional cure. This would be life-changing for many people not only due to the control of the virus but because it could dispel a lot of the stigma associated with having CHB.

Although current treatments can mitigate these risks, they come with the burden of taking medication every single day, of regular blood work and clinic appointments, not to mention the financial expense. Unfortunately, these burdens can sometimes be too great, and some people fall out of care.

From a healthcare professional (HCP) standpoint, a functional cure could eliminate the need to perform long-term monitoring and care, which is a big commitment. With how complicated healthcare is, lapses happen often, and patients who fall out of care may develop cirrhosis and not even know it.

Ultimately, this is something that the whole community is really anticipating.

Bridging the Dream With Reality
As we work towards the development of a functional cure, there are many things we need to do now to get more people diagnosed and into care. Based on the 2022 Global Hepatitis Report, only 13% of people living with CHB have been diagnosed, and 3% have received treatment; as a result, liver cancer rates are still on the rise.

The CDC now recommends universal HBV screening and vaccination. Now is the time to scale up screening so more know their HBV status. Most of the liver societies are also updating HBV treatment guidelines this year and we anticipate the expansion of treatment eligibility. 

In addition, we have a new tool, quantitative hepatitis B surface antigen (qHBsAg) that measures activity of the virus in the liver. This adds to our understanding of the virus, especially while a patient is receiving treatment. Someone on antiviral treatment may have undetectable HBV DNA, but they have a high qHBsAg, meaning there is still virus in the liver. It confirms that a patient should remain on the antivirals and if treatment were to be discontinued, they have a high chance of viral rebound.

Earlier Treatment
We are seeing an evolution in our approach in HBV treatment with an openness to starting antivirals earlier. Antivirals are safe, effective at suppressing the virus, and have become more affordable with the availability of generic medications.

In the past, there was concern about the high risk of developing resistance with lamivudine, but that is less of a concern with tenofovir and entecavir. Although our current treatments are not a cure, controlling viral replication is important for preventing the inflammation that drives development of cirrhosis and cancer, subsequently improving patient outcomes.

Our previous strict approach of obtaining frequent labs to “prove people needed to be treated” led to many individuals not receiving treatment and falling out of care. Many people living with CHB were told by their HCPs that they didn’t need medication, and some resorted to taking ineffective and potentially harmful herbal medications and supplements. Some experts believe that HCPs should approach HBV as “prove to me you don’t need to be treated.”

To me, the risk-benefit balance of initiating treatment has shifted. I want to empower HCPs to offer treatment to all people living with CHB, evaluate risks and benefits individually and use shared decision-making when discussing therapy.

Empowering Patients           
We are seeing people living with CHB being more empowered and wanting to be more involved in their disease management.

Shared decision-making is important if we are to deliver person-centered care and not paternalistic medicine. It is important to let patients know that there is a decision to be made about treatment and invite their participation. We need to ask what is important to them, offer them options, and then come up with a plan together. Some patients want to be proactive and receive treatment even if their risk may be low, whereas there may be others who prefer close monitoring over treatment.

For those who start treatment, adherence must be emphasized as there is a risk of hepatitis flare if treatment is stopped. Although many people discontinue treatment and remain asymptomatic, there is a small percentage of people who experience much worse outcomes, including fulminant liver failure. That being said, HBV treatment is quite easy to take; our current antivirals are a single pill, taken once a day, with very few side effects.

Whether one is on treatment or not, patients should be counseled that CHB is a dynamic disease that requires monitoring and liver cancer screening.

Role of Primary Care Providers
We will only achieve hepatitis elimination if primary care providers have a greater role in HBV care and management. Shifting hepatitis care from specialist to frontline HCPs is important to expand access and help retain more people in care, especially those without access to a specialist. 

For HCPs who are not ready to manage HBV on their own, I encourage you to develop a partnership with hepatology or infectious disease specialists. Shared care can mean having a specialist do an initial evaluation and the primary care provider doing ongoing monitoring of HBV DNA and ALT (when they are doing other lab work), liver cancer imaging (when being evaluated for other cancer screening) and medication refill management. If there are changes, the patient can be reevaluated by the specialist.

As a primary care provider myself, I can say that HBV management is much easier to treat than other conditions I see. For example, with diabetes, there are more types of medication to choose from and many have more adverse events and drug interactions. It has been very satisfying to provide HBV care as part of primary care and I consider it part of a whole person approach; it adds little additional time to a visit and patients are very grateful. We complete breast and colon cancer prevention as part of our work, and HBV care is also liver cancer prevention.

Ultimately, I think we have all the tools to get HBV eliminated by 2030, but it requires us to get more care to more individuals with CHB. We should not be delaying HBV treatment as we wait for a functional cure; we should be doing what we can now—diagnosing and providing HBV treatment to those in our care.

Learn More
To learn more about functional cure and the potential benefits for our community, join me and Drs Jordan Feld and Norah Terrault at our live symposium at DDW 2025 in San Diego, California. You can participate in person or via live simulcast. 

Your Thoughts
How do you discuss the potential for a functional cure for HBV with your patients? Leave a comment to join the discussion.