Chronic hepatitis B is a viral infection affecting the liver. While current medications can control the virus, they rarely lead to a complete cure. This has prompted a significant shift in research, moving from long-term management toward the pursuit of definitive solutions. The scientific community is now exploring new therapeutic avenues aimed at clearing the virus from the body.
The Goal of Modern Hepatitis B Therapy
Standard treatments, like nucleoside/nucleotide analogues (NAs) and interferons, effectively suppress the hepatitis B virus (HBV). However, these treatments must be taken for life for most individuals because they seldom eliminate the virus. The annual clearance rate of the hepatitis B surface antigen (HBsAg) with NA therapy is only about 1%. This persistence means the risk of liver complications like cirrhosis and cancer remains, even with a suppressed virus.
This therapeutic gap has led researchers to a new primary objective: a “functional cure.” A functional cure is the sustained loss of HBsAg in the blood for at least six months after treatment ends. This outcome indicates the immune system has gained control over the virus, allowing for the safe cessation of therapy. This is distinct from a “sterilizing cure,” which would eliminate all viral genetic material, including the persistent covalently closed circular DNA (cccDNA). A sterilizing cure is not a realistic short-term goal, so the functional cure is the focus of drug development.
Emerging Therapeutic Strategies
The search for a functional cure has led to several new classes of drugs, each designed to attack the hepatitis B virus differently. These strategies can be categorized by whether they target the virus directly or modulate the body’s immune response.
Directly Targeting the Virus
One approach involves directly interfering with the virus’s ability to produce its proteins. RNA interference (RNAi) therapies use small interfering RNA (siRNA) to silence specific viral genes. These molecules guide a cellular complex to destroy the virus’s messenger RNA (mRNA) before it can make new viral proteins, leading to a rapid decline in HBsAg levels. Another strategy uses Capsid Assembly Modulators (CAMs), which disrupt the formation of the virus’s capsid, a core particle needed for replication and establishing the cccDNA reservoir.
Boosting the Immune System
Other therapies focus on stimulating the patient’s immune system. Therapeutic vaccines are being developed to train the immune system to recognize and attack HBV-infected cells; unlike preventative vaccines, they treat an existing infection. Immune modulators, such as Toll-like receptor (TLR) agonists, activate the innate immune system to create a stronger anti-viral response.
Blocking Viral Entry
A third category of drugs prevents the virus from spreading to new liver cells. Entry inhibitors, like the approved drug Bulevirtide, block the specific receptor on liver cells that HBV uses to gain entry. While not a cure on their own, these drugs can be part of a broader strategy to contain the infection by preventing new cells from being infected.
The Role of Combination Therapy
A single drug is unlikely to achieve a functional cure for most people with chronic hepatitis B. Therefore, the future of treatment lies in combination therapy, using multiple drugs that attack the virus from different angles simultaneously. This approach is similar to successful multi-drug regimens for HIV, as combining agents with different mechanisms can create a powerful synergistic effect.
For example, a potential combination could pair a nucleoside analogue, which suppresses viral DNA replication, with an RNAi therapeutic that reduces HBsAg production. An immune modulator could also be added to this mix to help clear remaining infected cells. Studies combining NAs with interferons have already shown greater reductions in viral markers compared to monotherapy. Research continues to determine the optimal combinations and timing of these drugs.
Accessing and Understanding Clinical Trials
Most new hepatitis B treatments are still in development and are accessible to patients through clinical trials. These research studies determine the safety and effectiveness of a new drug before it can be approved. The trials are conducted in phases: Phase 1 focuses on safety in small groups; Phase 2 evaluates effectiveness in larger groups; and Phase 3 confirms effectiveness and monitors side effects in large populations, often comparing the new treatment to standard therapies.
Individuals interested in these new options should first speak with their hepatologist or gastroenterologist. These specialists can provide information about ongoing trials and assess a patient’s eligibility. Online resources like the Hepatitis B Foundation and government databases like ClinicalTrials.gov also provide searchable listings of studies. These resources help patients learn about the latest advances and potentially participate in research.