The following is a summary of “Evidence of Residual Ongoing Viral Replication in Chronic Hepatitis B Patients Successfully Treated With Nucleos(t)ide Analogs,” published in the March 2023 issue of Infectious Diseases by Yu, et al.

The standard treatment for chronic hepatitis B involves nucleos(t)ide analogs (NAs). However, despite years of treatment, a cure is rare. For a study, researchers sought to investigate whether viral replication is completely stopped and how long the covalently closed circular DNA (cccDNA) remains in patients successfully treated with NAs.

They collected serum samples over time and liver biopsies from patients successfully treated with NAs. They used deep sequencing to enumerate viral variants in serum HBV RNA and directly visualized viral replication intermediates in hepatocytes using in situ hybridization. They also estimated the apparent half-life of each cccDNA.

Out of 6 successfully treated patients, 3 showed evidence of a small proportion of virus evolution, while most variants remained identical or had a similar degree of divergence over time. The apparent half-life of variants was estimated to be approximately 7.42 weeks to infinite. In addition, four out of seven liver needle biopsies showed that hepatocytes remained positive for cytoplasmic nucleocapsids-associated relaxed circular DNA.

They concluded that, even after prolonged treatment, a small proportion of the cccDNA reservoir was continuously replenished by low-level HBV replication, while a large proportion of the cccDNA reservoir persisted over time.

Reference: academic.oup.com/jid/article-abstract/227/5/675/6955920?redirectedFrom=fulltext