My Take on Viral Hepatitis Treatment Advances From AASLD 2022: European Perspective

Key Takeaways

• HCV treatments have excellent cure rates, but HCV identification and linkage to care after a positive test are still lagging.
• Early use of tenofovir disoproxil fumarate in pregnancy in combination with active infant immunization is an effective strategy for preventing vertical transmission of HBV.
• Novel therapeutics for hepatitis delta virus have demonstrated safety and efficacy and their expanded use is urgently awaited.

We saw many interesting studies at the recent AASLD 2022 meeting that confirmed best practices and highlighted advances in treatment and care of patients with viral hepatitis.

Hepatitis C
Data continue to demonstrate that we have excellent drug combinations available for treating and curing patients infected with hepatitis C virus (HCV). There were also studies that evaluated HCV treatment in special populations (people experiencing homelessness, people who inject drugs) and demonstrated the ability to achieve high sustained virologic responses in these patient populations.

The issues that remain in treating patients with HCV are improving diagnosis rates and linking patients into care when they test positive for HCV. Studies continue to document how important it is to have an interdisciplinary team of healthcare professionals—social workers, psychologists, psychiatrists, nurses, pharmacists—to support care linkages and ongoing engagement in care for patients with HCV.

Care linkages are especially important in correctional facilities. In Europe, it varies by country how the drug costs are reimbursed in correctional facilities, so treatment of imprisoned patients can be limited. However, test-and-treat data in correctional populations in Spain have demonstrated that HCV eradication in this population can be achieved.

Hepatitis B
We saw studies that confirmed that the use of tenofovir disoproxil fumarate (TDF) in preventing vertical transmission of hepatitis B virus (HBV) is safe and effective. One study showed that when the pregnant person is treated with TDF early in pregnancy, active vaccination of the infant may be all that is required. This is an important takeaway for resource-limited settings that may not have access to HBIg for passive immunization of infants at birth. However, in countries with enough resources, we should continue to provide active and passive immunization of infants born to mothers with HBV.

There are many promising HBV therapeutics in the development pipeline; one of the most interesting to me is the development of antisense and small-interfering RNA molecules targeting hepatitis B surface antigen (HBsAg) expression. These will probably be used in combination with capsid assembly modulator inhibitors and nucleos(t)ide analogues.

Despite progress being made in drug development for HBV, the biggest need remains for a drug that can best be described as an “optimal immune stimulator,” which may be a therapeutic vaccine and/or toll-like receptor agonists. We expect to hear more on these data in the future. 

Hepatitis Delta
We continue to need more data to confirm hepatitis delta virus (HDV) epidemiology. It is estimated that 1% to 2% of patients who are HBsAg positive have a concurrent replicative HDV infection. For us to better estimate HDV prevalence, we need to advocate for double reflex testing. So anyone who is HBsAg positive should be tested for anti-HDV, and if anti-HDV positive, they need HDV RNA testing for viremia. This is extremely important in countries where hepatitis guidelines do not specify double reflex testing for HDV in all patients with HBsAg positivity because this leads to HDV screening tests not being reimbursed and low testing rates.

HDV is the most progressive form of viral hepatitis and treatment is urgent—the clinical course leads to early complications of hepatocellular carcinoma, liver decompensation, and the need for liver transplantation. In Europe, we have conditional authorization of bulevirtide, an entry inhibitor, and a lot of real-world data to support its use.

In the French early access program, where patients were treated with either bulevirtide monotherapy or bulevirtide with peginterferon, patients who received bulevirtide plus peginterferon had a better virologic response at 1 year compared with bulevirtide monotherapy. However, at 2 years, the bulevirtide group had a similar virologic response rate to the combination therapy group. If these monotherapy data can be confirmed, bulevirtide monotherapy will likely be the preferred regimen moving forward.

We also saw exciting data presented on lonafarnib at the AASLD meeting, including a case series of 5 patients who achieved functional cure. We are expecting more data soon with topline results from a larger lonafarnib study that evaluated 400 patients with HDV. These data are also expected to be presented at the European Association for the Study of the Liver meeting in 2023.

Your Thoughts?
What do you think were the most practice-changing viral hepatitis data presented at AASLD 2022? Join the conversation by leaving a comment below.