1 Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada.
2 Institute of Medical Science, University of Toronto, Toronto, Canada.
3 Department of Gastroenterology & Hepatology, Erasmus Medical Centre Rotterdam, Rotterdam, Netherlands.
4 University Hospital Leipzig, Department of Gastroenterology and Rheumatology, Section of Hepatology, Leipzig, Germany.
5 Department of Internal Medicine 3, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
6 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
BACKGROUND: Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA) which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients.
METHODS: HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA below 2,000 IU/ml and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg.
RESULTS: Mean HBV-RNA at baseline was 4.4 (SD 1.2) log10 c/mL. At week 12, HBV-RNA declined by -1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to non-responders early at week 12 (-2.0 [1.2] vs -1.5 [1.1] log10 c/mL, P=0.04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P=0.01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (0.82 and 0.80, P<0.001) and a weak correlation with HBsAg (0.25). At week 12, HBV-RNA was significantly lower among patients with lower HBsAg (< 100 IU/ml) or HBsAg-loss at week 144.
CONCLUSIONS: During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a fast and significant decline that correlates with treatment response and HBsAg-loss at long-term follow-up.https://clinicaltrials.gov/ct2/show/NCT00114361, NCT00114361.