Hepatitis B & C: New Findings and the Emerging Path to a Functional Cure

 

 

The Global Burden of Viral Hepatitis

Viral hepatitis remains one of the leading causes of preventable death globally. Hepatitis B
virus (HBV) chronically infects more than 254 million people worldwide, causing nearly
900,000 deaths annually through cirrhosis and hepatocellular carcinoma (liver cancer).
Hepatitis C virus (HCV) infects approximately 58 million people globally, and was
responsible for 290,000 deaths in 2019.
The good news is that both diseases are now at pivotal treatment inflection points — HCV
has effectively been cured in the clinical sense, while HBV research in 2025 achieved
breakthroughs that bring a true functional cure closer than at any previous time in history.

 

 

Hepatitis C: A Virus We Can Now Cure

The development of direct-acting antivirals (DAAs) represents one of the greatest
achievements in the history of infectious disease medicine. In less than a decade, HCV
treatment moved from year-long, poorly tolerated interferon-based regimens (with 40–50%
cure rates and severe side effects) to 8–12 week oral tablet regimens achieving cure rates
exceeding 95%.
In June 2025, the FDA approved a label expansion for glecaprevir/pibrentasvir (Mavyret) —
making it the first and only DAA approved for acute HCV infection, treating patients in just 8
weeks with a 96% cure rate (M20-350 Phase 3 trial). This is a landmark because earlier
treatment of acute HCV prevents progression to chronic infection and liver damage.
The WHO has set a target of eliminating HCV as a public health threat by 2030 — an
ambitious goal that modelling studies suggest could prevent 15.1 million new infections and
1.5 million deaths. However, a 2025 Lancet trial and systematic review identified critical
barriers: HCV disproportionately affects high-risk populations (people who inject drugs,
incarcerated individuals) who face significant obstacles to testing and treatment access.
Reinfection after cure also remains a challenge when risk behaviours continue.
Canadian researchers in 2025 demonstrated that successful HCV treatment and cure
produces benefits far beyond liver health — cured patients showed significantly lower risk of
kidney disease, cardiovascular events, stroke, and neurocognitive decline, confirming that
HCV's damage extends systemically.

 

 

Hepatitis B: The Functional Cure Revolution

While HCV is now curable, HBV has been far more difficult to eliminate. Current standard-of-
care treatments — nucleos(t)ide analogues (NAs) such as tenofovir and entecavir —
effectively suppress viral replication and reduce the risk of cirrhosis and liver cancer, but
they do not eradicate the virus. This is because HBV establishes a stable reservoir of
covalently closed circular DNA (cccDNA) inside infected liver cells that persists indefinitely
and cannot be targeted by current NAs.
A functional cure — defined as sustained loss of hepatitis B surface antigen (HBsAg) and
undetectable HBV DNA 24 weeks after finite treatment — is now the clinical target. Current
NAs achieve functional cure in only about 1% of patients.

 

 

2025: Breakthrough Advances in Hepatitis B

Multiple new drug classes in advanced clinical trials are showing unprecedented HBsAg
reduction, bringing functional cure within reach:

 

 

RNA Interference (RNAi) Therapeutics

RNAi drugs silence HBV gene expression, dramatically reducing the viral antigen burden
that suppresses the immune system's ability to fight the virus. In Phase 2 trials, JNJ-3989
achieved over 1 log IU/mL HBsAg reduction in 98% of patients. AB-729 and VIR-2218
showed similarly potent HBsAg declines. These drugs are expected to be used in
combination strategies.

 

Bepirovirsen: GSK's Phase 3 Success

In January 2026, GSK announced positive results from the B-Well 1 and B-Well 2 Phase 3
trials of bepirovirsen — an antisense oligonucleotide that targets HBV RNA and reduces viral
antigen load. The trials met their primary endpoint, demonstrating a statistically significant
and clinically meaningful functional cure rate — significantly higher than standard of care
alone. Bepirovirsen has received Fast Track designation from the FDA, Breakthrough
Therapy designation in China, and SENKU designation in Japan.

 

 

Therapeutic Vaccines

The first patient was enrolled in June 2025 in the first clinical trial of TherVacB — a
therapeutic vaccine for chronic hepatitis B. Unlike preventive vaccines, therapeutic vaccines
aim to reactivate the patient's own immune response against HBV. A previous healthy
volunteer trial demonstrated a favourable safety profile and appropriate immune response.
BRII-179 (in combination with siRNA elebsiran) showed 40% of patients developing anti-HBs
antibodies — an extraordinary early result.

 

2025 EASL Guidelines: A New Treatment Paradigm

The 2025 European Association for the Study of the Liver (EASL) guidelines published in
August 2025 mark a significant shift toward biomarker-led, finite, personalised therapy for
chronic hepatitis B. Novel biomarkers including quantitative HBsAg (qHBsAg), HBcrAg, and
HBV RNA are now incorporated into treatment algorithms. Approximately 20–30% of
carefully selected non-cirrhotic HBeAg-negative patients may achieve sustained off-
treatment control after stopping NAs — a small but meaningful step toward functional cure
using existing drugs.

 

References

[1] Toma D, Anghel L, et al. Hepatitis C Virus: Epidemiological Challenges and Global Strategies for
Elimination. Viruses. 2025;17(8):1069. doi:10.3390/v17081069.
[2] HCPLive. Hepatitis in 2025: Year in Review. hcplive.com, December 2025.
[3] Marrapu S, Kumar R, et al. Hepatitis B functional cure: Current and future perspective. World J
Hepatol. 2025;17(10):110107. doi:10.4254/wjh.v17.i10.110107.
[4] GSK Press Release. B-Well 1 and B-Well 2 Phase III Trials for Bepirovirsen. gsk.com, January 2026.
[5] Liu T, Wang H, et al. Drug development for chronic hepatitis B functional cure: Recent progress.
World J Hepatol. 2025;17(4):105797. doi:10.4254/wjh.v17.i4.105797.
[6] Willner IR et al. Chronic hepatitis B in 2025: diagnosis, treatment and future directions.
PMC12681808. 2025.
[7] Roth D et al. Treatment options to support the elimination of hepatitis C. The Lancet. 2025.
doi:10.1016/S0140-6736(25)00097-2.