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28 Jul 2021

World Hepatitis Day: A new approach that could contribute to a future hepatitis B cure

Peer review: Cell Death and Disease
Funding: NHMRC

Researchers from the Walter and Eliza Hall Institute (WEHI) have identified a treatment strategy that could be included in cure strategies for hepatitis B (HBV). Doherty Institute scientists contributed to the study by developing a preclinical model that permits studies of the impact of the drugs for different HBV genotypes and variants.

Current treatment effectively supresses viral replication in patients infected with HBV but do not target the nuclear reservoir of viral DNA, known as cccDNA. This is where the infection persists and can lead to liver cancer.

HBV is one of the major causes of liver scarring, or cirrhosis, and liver cancer. In Australia an estimated 240,000 people have the condition and a cure remains elusive.

Recently published in Cell Death and Disease, the research team adapted a mouse model that sustained prolonged HBV replication allowing for assessment of cccDNA-like structures in immune-competent mice.

“A major barrier to the development and evaluation of such curative therapies is the lack of appropriate robust preclinical models which enable investigation of cccDNA dynamics,” said Thao Huynh, PhD student from the Revill Group at the Doherty Institute.

This model uses hydrodynamic injection of HBV genome monomers that can be readily adapted for investigation of any HBV genotype, serotype or variant.

“Using this model, we demonstrated that clinical-stage, orally administered pro-apoptotic drugs or monovalent IAP (Inhibitor of Apoptosis Proteins) inhibitors, had the capacity to inhibit HBV replication and eliminate persistent infection,” Ms Huynh explained.

This finding was confirmed by Dr Tokameh Mahmoudi from Erasmas MC Rotterdam, and Doherty Institute Professor Elizabeth Vincan and Professor Joe Torresi in HBV-infected primary human liver organoids.

“A cure for HBV is a priority to reduce disease-related morbidity and mortality and to eliminate the need for lifelong antiviral therapy in people with chronic active HBV hepatitis” said co-author Professor Peter Revill, laboratory head at the Doherty Institute.

This study was led by WEHI’s Professor Marc Pellegrini and his team including Michelle Clark, Dr Greg Ebert.

Today is World Hepatitis Day, a day to raise awareness of the global burden of viral hepatitis and to influence real change. The theme for 2021 is ‘Hepatitis Can’t Wait’.