Q&A: Expert discusses current state of hepatitis D, challenges in elimination efforts

Healio spoke with Meg Doherty, MD, MPH, PhD, Director Global HIV, Hepatitis and STI Programmes at WHO, about elimination efforts for hepatitis D, including how hepatitis D would be affected by WHO Global Hepatitis Elimination goals and what U.S. physician can do to help work towards hepatitis elimination.

Healio: What efforts are being made to eliminate hepatitis D?

Doherty: Hepatitis D is an inflammation of the liver caused by the hepatitis D virus (HDV), which requires hepatitis B virus (HBV) for its replication. Hepatitis D infection cannot occur in the absence of hepatitis B virus. HDV-HBV coinfection is considered the most severe form of chronic viral hepatitis due to more rapid progression towards hepatocellular carcinoma and liver-related death. Vaccination against hepatitis B is the current means of preventing HDV infection.

WHO did a systematic review to document geographic and population priorities, and HDV is now more prominent in the Global Health Sector strategies on, respectively, HIV, viral hepatitis and sexually transmitted infections for the period 2022-2030.

We are also developing updated guidance for HDV testing and diagnosis and treatment as part of updated HBV guidance.

WHO is [also] supporting high burden countries like Mongolia for elimination.

Healio: What additional work is needed to achieve hepatitis D elimination?

Doherty: Two issues have limited clinical management:

• lack of standardized virological methods to diagnose and monitor the infection; and
• lack of effective therapy to treat the liver disease caused by Hepatitis D virus (HDV) have limited the progress in clinical management.

Current treatment with recombinant or pegylated interferon alfa therapy can inhibit HDV replication and reduce liver inflammation and disease progression in 20–25% of patients. However, this treatment is characterized by poor response rates and limited efficacy, and is contraindicated in more advanced liver disease. It also has significant side effects and may induce associated autoimmune hepatitis.

Additional work is also needed to develop effective diagnostic tools for both serological and molecular diagnosis as well as effective antiviral therapy.

Recent developments in understanding and targeting therapeutic efforts have opened new hope for patients with hepatitis D. Bulevirtide [Hepcludex, Gilead Sciences] is a new entry inhibitor that has been approved by the European Medicines Agency for use in treatment of hepatitis D. Studies with this drug showed a decline in the level of hepatitis D viral load and normalization of abnormal liver function tests. However, it must be injected subcutaneously and is also costly.

A number of other novel products are also under investigation.

Healio: Which patients are most vulnerable to hepatitis D?

Doherty: Globally, HDV affects nearly 5% of people who have a chronic infection with HBV.

HDV infection occurs when people become infected with both hepatitis B and D simultaneously (co-infection) or get hepatitis D after first being infected with hepatitis B (super-infection). Populations that are more likely to have HBV and HDV co-infection include indigenous populations in endemic areas, recipients of haemodialysis and people who inject drugs.

Healio: How do hepatitis B elimination efforts affect hepatitis D elimination?

Doherty: While WHO does not have specific recommendations on hepatitis D, prevention of HBV transmission through hepatitis B immunization, including a timely birth dose, additional antiviral prophylaxis for eligible pregnant women, blood safety, safe injection practices in health care settings and harm reduction services with clean needles and syringes are effective in preventing HDV transmission. Hepatitis B immunization does not provide protection against HDV for those already infected with HBV.

Healio: How can primary care physicians aide in hepatitis elimination?

Doherty: It is important that primary care physicians be aware of Hepatitis D co-infection (or super infection) of patients living with HBV, especially in HDV endemic areas or with features of chronic liver disease and evaluate the need for testing and diagnosis and referral to specialist care.

Healio: Which elimination efforts are most needed in the United States?

Doherty: HDV infection is uncommon in the United States, where most cases occur among people who migrate or travel to the U.S. from countries with high HDV endemicity. However, because hepatitis D is not a nationally notifiable condition, the actual number of hepatitis D cases in the U.S. is unknown. Elimination efforts needed are thus: awareness raising, advocacy, epidemiological surveys to identify population and sub-populations most at risk, improvement in the design and development of both diagnostic tests and effective treatment.

References:

Stockdale A, et al. J Hepatol. 2020;doi:10.1016/j.jhep.2020.04.008.