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30 Nov 2022

Hepatitis B virus genetic diversity predicts potential to achieve functional cure

What if there was a way to predict which patients are more likely to achieve functional cure of chronic hepatitis B virus infection? 

Doherty Institute scientists have done just that by uncovering that people living with hepatitis B virus (HBV) that is less diverse are more likely to achieve functional cure on treatment.  

It is estimated that 296 million people live with CHB infection around the world. CHB can lead to cirrhosis, liver failure and liver cancer, and 887,000 people were estimated to have died in 2015 directly from CHB-related conditions.  

“There is no cure for CHB but, on rare occasions, current antiviral treatment can achieve what we call ‘functional cure’ - that is the loss of hepatitis B surface antigen (HBsAg), a biomarker indicative of the virus in the blood,” explained the Royal Melbourne Hospital’s Professor Peter Revill, Senior Medical Scientist in the Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute. 

“We wanted to know how likely a person with CHB is to reach functional cure during their antiviral therapy.” 

HBV is a DNA virus that has an RNA phase, which is critical for viral replication. When the RNA is copied to DNA, there is no correction of errors, and many different versions (variants) of the HBV genome are produced. A haplotype number (HN) is a measure of this diversity – the lower the number, the less diverse the viral genome. 

Using deep sequencing, the team studied hepatitis B virus variants in people living with HBV to identify predictors of disease outcome and treatment response. 

In this world-first study published in the Alimentary Pharmacology & Therapeutics medical journal, the researchers found that a lower haplotype number (≤2) in a patient was associated with a higher chance to achieve functional cure on antiviral therapy. 

“This is the first study to show that haplotype number at baseline predicts which patients may, or may not, achieve functional cure on current antiviral therapy,” said the Royal Melbourne Hospital’s Dr Josef Wagner, Bioinformatician in VIDRL in the Doherty Institute and lead author of the paper. 

“At present our findings are limited to hepatitis B virus genotypes A and D, and further studies are required with additional HBV genotypes.” 

The Royal Melbourne Hospital’s Dr Margaret Littlejohn, Senior Medical Scientist in VIDRL at the Doherty Institute said that this is a great step in providing tools for clinicians to treat their patients more efficiently. 

“The SARS-CoV-2 pandemic has normalised the use of next-generation (deep) sequencing for rapid analysis of viral isolates on an unprecedented scale, including haplotype studies,” Dr Littlejohn explained. 

“For patients living with chronic hepatitis B, we can now establish the HBV haplotype population from a blood serum sample in a fast and efficient manner, predicting which patients may or may not achieve functional cure on treatment in some settings, thereby providing clinicians with an effective biomarker of treatment response.” 

The team acknowledges the support from Gilead Sciences, USA.

Funding: Gilead Sciences, USA 
DOI: 10.1111/apt.17299