In patients with chronic hepatitis B infection, treatment with pegylated interferon (PEG-IFN) has effected a fast and significant decline in hepatitis B virus RNA (HBV-RNA) that correlates with treatment response and hepatitis B surface antigen (HBsAg) loss, according to an international randomized controlled trial published in Clinical Infectious Diseases.

HBV-RNA is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular DNA and is an important target for PEG-IFN for functional cure. However, the role of serum HBV-RNA in hepatitis B e-antigen (HBeAg)-negative chronic HBV infection to predict response and functional cure by PEG-IFN is unclear. Therefore, researchers investigated the association of serum HBV-RNA levels with response to PEG-IFN α-2a for 48 weeks in 133 HBeAg-negative patients with chronic HBV and compared its performance with other circulating HBV biomarkers.

The researchers found that mean HBV-RNA levels decreased from 4.4 log10 c/mL at baseline by -1.6 log10 c/mL at week 12. In addition, HBV-RNA levels can predict nonresponse as early as week 12 of treatment and demonstrated much lower levels among patients who achieved HBsAg loss. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and hepatitis B core-related antigen, and a weak correlation with HBsAg.   

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“In conclusion, our study shows that HBV-RNA levels decrease rapidly and profoundly in HBeAg-negative patients treated with PEG-IFN,” stated the study authors. They added that, “While the role of HBV-RNA in clinical use is still in development, this is of particular interest in novel treatment approaches, and its biological role needs to be further researched as the newly developed therapeutic agents aim for a sustained off-treatment response or even functional cure, a goal similar for finite PEG-IFN treatment.”

Disclosure: This clinical trial was supported by F. Hoffmann-La Roche Ltd. Please see the original reference for a full list of authors’ disclosures.


Farag MS, van Campenhout MJH, Pfefferkorn M, et al. Hepatitis B virus RNA as early predictor for response to PEGylated interferon alfa in HBeAg negative chronic hepatitis B [published online January 8, 2020]. Clin Infect Dis. doi: 10.1093/cid/ciaa013